Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma
Abstract
:1. Introduction
1.1. General Considerations on miRNAs and Chemoresistance
1.2. Possible Mechanisms of the Action of miRNAs in Multiple Myeloma Chemoresistance
1.3. miRNAs and Chemoresistance to Antimyeloma Drugs
2. Challenges and Future Perspectives
3. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Ettari, R.; Zappalà, M.; Grasso, S.; Musolino, C.; Innao, V.; Allegra, A. Immunoproteasome-selective and non-selective inhibitors: A promising approach for the treatment of multiple myeloma. Pharm. Ther. 2018, 182, 176–192. [Google Scholar] [CrossRef]
- Allegra, A.; Alonci, A.; Gerace, D.; Russo, S.; Innao, V.; Calabrò, L.; Musolino, C. New orally active proteasome inhibitors in multiple myeloma. Leuk. Res. 2014, 38, 1–9. [Google Scholar] [CrossRef] [PubMed]
- Caserta, S.; Innao, V.; Musolino, C.; Allegra, A. Immune checkpoint inhibitors in multiple myeloma: A review of the literature. Pathol. Res. Pr. 2020, 216, 153114. [Google Scholar] [CrossRef]
- Allegra, A.; Innao, V.; Allegra, A.G.; Leanza, R.; Musolino, C. Selective Inhibitors of Nuclear Export in the Treatment of Hematologic Malignancies. Clin. Lymphoma Myeloma Leuk. 2019, 19, 689–698. [Google Scholar] [CrossRef] [PubMed]
- Allegra, A.; Penna, G.; Innao, V.; Greve, B.; Maisano, V.; Russo, S.; Musolino, C. Vaccination of multiple myeloma: Current strategies and future prospects. Crit. Rev. Oncol. Hematol. 2015, 96, 339–354. [Google Scholar] [CrossRef]
- Allegra, A.; Penna, G.; Alonci, A.; Russo, S.; Greve, B.; Innao, V.; Minardi, V.; Musolino, C. Monoclonal antibodies: Potential new therapeutic treatment against multiple myeloma. Eur. J. Haematol. 2013, 90, 441–468. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allegra, A.; Sant’antonio, E.; Penna, G.; Alonci, A.; D’Angelo, A.; Russo, S.; Cannavò, A.; Gerace, D.; Musolino, C. Novel therapeutic strategies in multiple myeloma: Role of the heat shock protein inhibitors. Eur. J. Haematol. 2011, 86, 93–110. [Google Scholar] [CrossRef]
- Bolli, N.; Avet-Loiseau, H.; Wedge, D.C.; Van Loo, P.; Alexandrov, L.B.; Martincorena, I.; Dawson, K.J.; Iorio, F.; Nik-Zainal, S.; Bignell, G.R.; et al. Heterogeneity of genomic evolution and mutational profiles in multiple myeloma. Nat. Commun. 2014, 5, 2997. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Krzeminski, P.; Corchete, L.A.; Garcia, J.L.; Lopez-Corral, L.; Ferminan, E.; Garcia, E.M.; Martín, A.A.; Hernández-Rivas, J.M.; García-Sanz, R.; San Miguel, J.F.; et al. Integrative analysis of DNA copy number, DNA methylation and gene expression in multiple myeloma reveals alterations related to relapse. Oncotarget 2016, 7, 80664–80679. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Neri, P.; Ren, L.; Azab, A.K.; Brentnall, M.; Gratton, K.; Klimowicz, A.C.; Lin, C.; Duggan, P.; Tassone, P.; Mansoor, A.; et al. Integrin beta7-mediated regulation of multiple myeloma cell adhesion, migration, and invasion. Blood 2011, 117, 6202–6213. [Google Scholar] [CrossRef] [Green Version]
- Kikuchi, J.; Koyama, D.; Wada, T.; Izumi, T.; Hofgaard, P.O.; Bogen, B.; Furukawa, Y. Phosphorylation-mediated EZH2 inactivation promotes drug resistance in multiple myeloma. J. Clin. Investig. 2015, 125, 4375–4390. [Google Scholar] [CrossRef]
- Shain, K.H.; Dalton, W.S. Environmental-mediated drug resistance: A target for multiple myeloma therapy. Expert Rev. Hematol. 2009, 2, 649–662. [Google Scholar] [CrossRef] [PubMed]
- Shain, K.H.; Dalton, W.S.; Tao, J. The tumor microenvironment shapes hallmarks of mature B-cell malignancies. Oncogene 2015, 34, 4673–4682. [Google Scholar] [CrossRef] [Green Version]
- Manier, S.; Sacco, A.; Leleu, X.; Ghobrial, I.M.; Roccaro, A.M. Bone marrow microenvironment in multiple myeloma progression. J. Biomed. Biotechnol. 2012, 2012, 157496. [Google Scholar] [CrossRef] [PubMed]
- Abdi, J.; Chen, G.; Chang, H. Drug resistance in multiple myeloma: Latest findings and new concepts on molecular mechanisms. Oncotarget 2013, 4, 2186–2207. [Google Scholar] [CrossRef] [Green Version]
- Allegra, A.; Alonci, A.; Campo, S.; Penna, G.; Petrungaro, A.; Gerace, D.; Musolino, C. Circulating microRNAs: New biomarkers in diagnosis, prognosis and treatment of cancer (review). Int. J. Oncol. 2012, 41, 1897–1912. [Google Scholar] [CrossRef] [Green Version]
- Pedroza-Torres, A.; Romero-Córdoba, S.L.; Justo-Garrido, M.; Salido-Guadarrama, I.; Rodríguez-Bautista, R.; Montaño, S.; Muñiz-Mendoza, R.; Arriaga-Canon, C.; Fragoso-Ontiveros, V.; Álvarez-Gómez, R.M.; et al. MicroRNAs in Tumor Cell Metabolism: Roles and Therapeutic Opportunities. Front. Oncol. 2019, 9, 1404. [Google Scholar] [CrossRef] [Green Version]
- Turchinovich, A.; Samatov, T.R.; Tonevitsky, A.G.; Burwinkel, B. Circulating miRNAs: Cell-cell communication function? Front. Genet. 2013, 4, 119. [Google Scholar] [CrossRef] [Green Version]
- Kosaka, N.; Yoshioka, Y.; Hagiwara, K.; Tominaga, N.; Katsuda, T.; Ochiya, T. Trash or Treasure: Extracellular microRNAs and cell-to-cell communication. Front. Genet. 2013, 4, 173. [Google Scholar] [CrossRef] [Green Version]
- Valadi, H.; Ekström, K.; Bossios, A.; Sjöstrand, M.; Lee, J.J.; Lötvall, J.O. Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between Cells. Nat. Cell Biol. 2007, 9, 654–659. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Suzuki, H.I.; Katsura, A.; Matsuyama, H.; Miyazono, K. MicroRNA regulons in tumor microenvironment. Oncogene 2015, 34, 3085–3094. [Google Scholar] [CrossRef] [Green Version]
- Allegra, A.; Musolino, C.; Tonacci, A.; Pioggia, G.; Gangemi, S. Interactions between the MicroRNAs and Microbiota in Cancer Development: Roles and Therapeutic Opportunities. Cancers (Basel) 2020, 12, 805. [Google Scholar] [CrossRef] [Green Version]
- Campo, S.; Allegra, A.; D’Ascola, A.; Alonci, A.; Scuruchi, M.; Russo, S.; Avenoso, A.; Gerace, D.; Campo, G.M.; Musolino, C. MiRNome expression is deregulated in the peripheral lymphoid compartment of multiple myeloma. Br. J. Haematol. 2014, 165, 801–813. [Google Scholar] [CrossRef]
- Qin, Y.; Zhang, S.; Deng, S.; An, G.; Qin, X.; Li, F.; Xu, Y.; Hao, M.; Yang, Y.; Zhou, W.; et al. Epigenetic silencing of miR-137 induces drug resistance and chromosomal instability by targeting AURKA in multiple myeloma. Leukemia 2017, 31, 1123–1135. [Google Scholar] [CrossRef] [PubMed]
- Dupere-Richer, D.; Licht, J.D. Epigenetic regulatory mutations and epigenetic therapy for multiple myeloma. Curr. Opin. Hematol. 2017, 24, 336–344. [Google Scholar] [CrossRef] [PubMed]
- Zhang, B.; Pan, X.; Cobb, G.P.; Anderson, T.A. microRNAs as oncogenes and tumor suppressors. Dev. Biol. 2007, 302, 1–12. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, W.; Dolan, M.E. The emerging role of microRNAs in drug responses. Curr. Opin. Mol. Ther. 2010, 12, 695–702. [Google Scholar] [PubMed]
- Ma, J.; Dong, C.; Ji, C. MicroRNA and drug resistance. Cancer Gene Ther. 2010, 17, 523–531. [Google Scholar] [CrossRef] [Green Version]
- Kasinski, A.L.; Slack, F.J. Potential microRNA therapies targeting Ras, NFkappaB and p53 signaling. Curr. Opin. Mol. Ther. 2010, 12, 147–157. [Google Scholar]
- Hermeking, H. MicroRNAs in the p53 network: Micromanagement of tumour suppression. Nat. Rev. Cancer. 2012, 12, 613–626. [Google Scholar] [CrossRef]
- Leotta, M.; Biamonte, L.; Raimondi, L.; Ronchetti, D.; Di Martino, M.T.; Botta, C.; Leone, E.; Pitari, M.R.; Neri, A.; Giordano, A.; et al. A p53-dependent tumor suppressor network is induced by selective miR-125a-5p inhibition in multiple myeloma cells. J. Cell Physiol. 2014, 229, 2106–2116. [Google Scholar] [CrossRef] [PubMed]
- Lionetti, M.; Agnelli, L.; Lombardi, L.; Tassone, P.; Neri, A. MicroRNAs in the Pathobiology of Multiple Myeloma. Curr. Cancer Drug Targets 2012, 12, 823–837. [Google Scholar] [CrossRef]
- Rossi, M.; Tagliaferri, P.; Tassone, P. MicroRNAs in multiple myeloma and related bone disease. Ann. Transl. Med. 2015, 3, 334. [Google Scholar] [PubMed]
- Tagliaferri, P.; Rossi, M.; Di Martino, M.T.; Amodio, N.; Leone, E.; Gulla, A.; Neri, A.; Tassone, P. Promises and Challenges of MicroRNA-based Treatment of Multiple Myeloma. Curr. Cancer Drug Targets 2012, 12, 838–846. [Google Scholar] [CrossRef] [Green Version]
- Ma, J.; Liu, S.; Wang, Y. MicroRNA-21 and multiple myeloma: Small molecule and big function. Med Oncol. 2014, 31, 94. [Google Scholar] [CrossRef] [PubMed]
- Tang, B.; Xu, A.; Xu, J.; Huang, H.; Chen, L.; Su, Y.; Zhang, L.; Li, J.; Fan, F.; Deng, J.; et al. MicroRNA-324-5p regulates stemness, pathogenesis and sensitivity to bortezomib in multiple myeloma cells by targeting hedgehog signaling. Int. J. Cancer 2018, 142, 109–120. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Xi, H.; Li, L.; Du, J.; An, R.; Fan, R.; Lu, J.; Wu, Y.X.; Wu, S.X.; Hou, J.; Zhao, L.M. hsa-miR-631 resensitizes bortezomib-resistant multiple myeloma cell lines by inhibiting UbcH10. Oncol. Rep. 2017, 37, 961–968. [Google Scholar] [CrossRef] [Green Version]
- Amodio, N.; Gallo Cantafio, M.E.; Botta, C.; Agosti, V.; Federico, C.; Caracciolo, D.; Ronchetti, D.; Rossi, M.; Driessen, C.; Neri, A.; et al. Replacement of miR-155 Elicits Tumor Suppressive Activity and Antagonizes Bortezomib Resistance in Multiple Myeloma. Cancers 2019, 11, 236. [Google Scholar] [CrossRef] [Green Version]
- Tian, F.; Zhan, Y.; Zhu, W.; Li, J.; Tang, M.; Chen, X.; Jiang, J. MicroRNA-497 inhibits multiple myeloma growth and increases susceptibility to bortezomib by targeting Bcl-2. Int. J. Mol. Med. 2019, 43, 1058–1066. [Google Scholar] [CrossRef]
- Yuan, X.; Ma, R.; Yang, S.; Jiang, L.; Wang, Z.; Zhu, Z.; Li, H. miR-520g and miR-520h overcome bortezomib resistance in multiple myeloma via suppressing APE1. Cell Cycle 2019, 18, 1660–1669. [Google Scholar] [CrossRef] [PubMed]
- Wang, X.; Li, C.; Ju, S.; Wang, Y.; Wang, H.; Zhong, R. Myeloma cell adhesion to bone marrow stromal cells confers drug resistance by microRNA-21 up-regulation. Leuk. Lymphoma 2011, 52, 1991–1998. [Google Scholar] [CrossRef]
- Abdi, J.; Rastgoo, N.; Li, L.; Chen, W.; Chang, H. Role of tumor suppressor p53 and micro-RNA interplay in multiple myeloma pathogenesis. J. Hematol. Oncol. 2017, 10, 169. [Google Scholar] [CrossRef] [Green Version]
- Ballabio, E.; Armesto, M.; Breeze, C.E.; Manterola, L.; Arestin, M.; Tramonti, D.; Hatton, C.S.; Lawrie, C.H. Bortezomib action in multiple myeloma: MicroRNA-mediated synergy (and miR-27a/CDK5 driven sensitivity)? Blood Cancer J. 2012, 2, e83. [Google Scholar] [CrossRef] [Green Version]
- Zhu, Y.X.; Tiedemann, R.; Shi, C.X.; Yin, H.; Schmidt, J.E.; Bruins, L.A.; Keats, J.J.; Braggio, E.; Sereduk, C.; Mousses, S.; et al. RNAi screen of the druggable genome identifies modulators of proteasome inhibitor sensitivity in myeloma including CDK5. Blood 2011, 117, 3847–3857. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ooi, C.H.; Oh, H.K.; Wang, H.Z.; Tan, A.L.; Wu, J.; Lee, M.; Rha, S.Y.; Chung, H.C.; Virshup, D.M.; Tan, P. A densely interconnected genome-wide network of microRNAs and oncogenic pathways revealed using gene expression signatures. PLoS Genet. 2011, 7, e1002415. [Google Scholar] [CrossRef] [Green Version]
- Lwin, T.; Zhao, X.; Cheng, F.; Zhang, X.; Huang, A.; Shah, B.; Zhang, Y.; Moscinski, L.C.; Choi, Y.S.; Kozikowski, A.P.; et al. A microenvironment-mediated c-Myc/miR-548m/HDAC6 amplification loop in non-Hodgkin B cell lymphomas. J. Clin. Investig. 2013, 123, 4612–4626. [Google Scholar] [CrossRef] [Green Version]
- Greco, C.; D’Agnano, I.; Vitelli, G.; Vona, R.; Marino, M.; Mottolese, M.; Zuppi, C.; Capoluongo, E.; Ameglio, F. c-MYC deregulation is involved in melphalan resistance of multiple myeloma: Role of PDGF-BB. Int. J. ImmunoPathol. Pharmacol. 2006, 19, 67–79. [Google Scholar] [CrossRef] [Green Version]
- Tao, J.; Zhao, X. c-MYC-miRNA circuitry: A central regulator of aggressive B-cell malignancies. Cell Cycle 2014, 13, 191–198. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, Y.; Chen, H.X.; Zhou, S.Y.; Wang, S.X.; Zheng, K.; Xu, D.D.; Liu, Y.T.; Wang, X.Y.; Wang, X.; Yan, H.Z.; et al. Sp1 and c-Myc modulate drug resistance of leukemia stem cells by regulating surviving expression through the ERK-MSK MAPK signaling pathway. Mol. Cancer 2015, 14, 56. [Google Scholar] [CrossRef] [Green Version]
- Labisso, W.L.; Wirth, M.; Stojanovic, N.; Stauber, R.H.; Schnieke, A.; Schmid, R.M.; Kramer, O.H.; Saur, D.; Schneider, G. MYC directs transcription of MCL1 and eIF4E genes to control sensitivity of gastric cancer cells toward HDAC inhibitors. Cell Cycle 2012, 11, 1593–1602. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saha, M.N.; Abdi, J.; Yang, Y.; Chang, H. miRNA-29a as a tumor suppressor mediates PRIMA-1Met-induced anti-myeloma activity by targeting c-Myc. Oncotarget 2016, 7, 7149–7160. [Google Scholar] [CrossRef] [PubMed]
- Ricci, M.S.; Kim, S.H.; Ogi, K.; Plastaras, J.P.; Ling, J.; Wang, W.; Jin, Z.; Liu, Y.Y.; Dicker, D.T.; Chiao, P.J.; et al. Reduction of TRAIL-induced Mcl- 1 and cIAP2 by c-Myc or sorafenib sensitizes resistant human cancer cells to TRAIL-induced death. Cancer Cell 2007, 12, 66–80. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, T.; Du, C.; Ma, X.; Sui, W.; Yu, Z.; Liu, L.; Zhao, L.; Li, Z.; Xu, J.; Wei, X.; et al. Polycomb-like Protein 3 Induces Proliferation and Drug Resistance in Multiple Myeloma and Is Regulated by miRNA-15a. Mol. Cancer Res. 2020, 18, 1063–1073. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Volkel, P.; Dupret, B.; Le Bourhis, X.; Angrand, P.O. Diverse involvement of EZH2 in cancer epigenetics. Am. J. Transl. Res. 2015, 7, 175–193. [Google Scholar]
- Lund, K.; Adams, P.D.; Copland, M. EZH2 in normal and malignant hematopoiesis. Leukemia 2014, 28, 44–49. [Google Scholar] [CrossRef] [PubMed]
- Beguelin, W.; Popovic, R.; Teater, M.; Jiang, Y.; Bunting, K.L.; Rosen, M.; Shen, H.; Yang, S.N.; Wang, L.; Ezponda, T.; et al. EZH2 is required for germinal center formation and somatic EZH2 mutations promote lymphoid transformation. Cancer Cell. 2013, 23, 677–692. [Google Scholar] [CrossRef] [Green Version]
- Pawlyn, C.; Bright, M.D.; Buros, A.F.; Stein, C.K.; Walters, Z.; Aronson, L.I.; Mirabella, F.; Jones, J.R.; Kaiser, M.F.; Walker, B.A.; et al. Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control. Blood Cancer J. 2017, 7, e549. [Google Scholar] [CrossRef]
- Agarwal, P.; Alzrigat, M.; Parraga, A.A.; Enroth, S.; Singh, U.; Ungerstedt, J.; Österborg, A.; Brown, P.J.; Ma, A.; Jin, J.; et al. Genome-wide profiling of histone H3 lysine 27 and lysine 4 trimethylation in multiple myeloma reveals the importance of Polycomb gene targeting and highlights EZH2 as a potential therapeutic target. Oncotarget 2016, 7, 6809–6823. [Google Scholar] [CrossRef] [Green Version]
- Kalushkova, A.; Fryknas, M.; Lemaire, M.; Fristedt, C.; Agarwal, P.; Eriksson, M.; Deleu, S.; Atadja, P.; Osterborg, A.; Nilsson, K.; et al. Polycomb target genes are silenced in multiple myeloma. PLoS ONE 2010, 5, e11483. [Google Scholar] [CrossRef]
- Rastgoo, N.; Pourabdollah, M.; Abdi, J.; Reece, D.; Chang, H. Dysregulation of EZH2/miR-138 axis contributes to drug resistance in multiple myeloma by downregulating RBPMS. Leukemia 2018, 32, 2471–2482. [Google Scholar] [CrossRef]
- Correia, C.; Schneider, P.A.; Dai, H.; Dogan, A.; Maurer, M.J.; Church, A.K.; Novak, A.J.; Feldman, A.L.; Wu, X.; Ding, H.; et al. BCL2 mutations are associated with increased risk of transformation and shortened survival in follicular lymphoma. Blood 2015, 125, 658–667. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yaya, K.; Hind, D.; Meryem, Q.; Asma, Q.; Said, B.; Sellama, N. Single nucleotide polymorphisms of multidrug resistance gene 1 (MDR1) and risk of chronic myeloid leukemia. Tumor Biol. 2014, 35, 10969–10975. [Google Scholar] [CrossRef]
- Tsubaki, M.; Komai, M.; Itoh, T.; Imano, M.; Sakamoto, K.; Shimaoka, H.; Takeda, T.; Ogawa, N.; Mashimo, K.; Fujiwara, D.; et al. By inhibiting Src, verapamil and dasatinib overcome multidrug resistance via increased expression of Bim and decreased expressions of MDR1 and survivin in human multidrug-resistant myeloma cells. Leuk. Res. 2014, 38, 121–130. [Google Scholar] [CrossRef] [PubMed]
- Zhang, X.; Chen, Y.; Zhao, P.; Zang, L.; Zhang, Z.; Wang, X. MicroRNA-19a functions as an oncogene by regulating PTEN/AKT/pAKT pathway in myeloma. Leuk. Lymphoma 2017, 58, 932–940. [Google Scholar] [CrossRef]
- Zhao, J.J.; Chu, Z.B.; Hu, Y.; Lin, J.; Wang, Z.; Jiang, M.; Chen, M.; Wang, X.; Kang, Y.; Zhou, Y.; et al. Targeting the miR-221-222/PUMA/BAK/BAX Pathway Abrogates Dexamethasone Resistance in Multiple Myeloma. Cancer Res. 2015, 75, 4384–4397. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hao, M.; Zhang, L.; An, G.; Sui, W.; Yu, Z.; Zou, D.; Xu, Y.; Chang, H.; Qiu, L. Suppressing miRNA-15a/-16 expression by interleukin-6 enhances drug-resistance in myeloma cells. J. Hematol. Oncol. 2011, 4, 37. [Google Scholar] [CrossRef] [Green Version]
- Leone, E.; Morelli, E.; Di Martino, M.T.; Amodio, N.; Foresta, U.; Gulla, A.; Rossi, M.; Neri, A.; Giordano, A.; Munshi, N.C.; et al. Targeting miR-21 inhibits in vitro and in vivo multiple myeloma cell growth. Clin. Cancer Res. 2013, 19, 2096–2106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Murray, M.Y.; Rushworth, S.A.; Zaitseva, L.; Bowles, K.M.; Macewan, D.J. Attenuation of dexamethasone-induced cell death in multiple myeloma is mediated by miR-125b expression. Cell Cycle 2013, 12, 2144–2153. [Google Scholar] [CrossRef]
- Yang, A.; Ma, J.; Wu, M.; Qin, W.; Zhao, B.; Shi, Y.; Jin, Y.; Xie, Y. Aberrant microRNA-182 expression is associated with glucocorticoid resistance in lymphoblastic malignancies. Leuk. Lymphoma 2012, 53, 2465–2473. [Google Scholar] [CrossRef] [PubMed]
- Wu, Y.; Zhu, X.; Shen, R.; Huang, J.; Xu, X.; He, S. miR-182 contributes to cell adhesion-mediated drug resistance in multiple myeloma via targeting PDCD4. Pathol. Res. Pr. 2019, 215, 152603. [Google Scholar] [CrossRef] [PubMed]
- Xu, Q.; Hou, Y.X.; Langlais, P.; Erickson, P.; Zhu, J.; Shi, C.X.; Luo, M.; Zhu, Y.; Xu, Y.; Mandarino, L.J.; et al. Expression of the cereblon binding protein argonaute 2 plays an important role for multiple myeloma cell growth and survival. BMC Cancer 2016, 16, 297. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fan, W.J.; Fan, Z.Q.; Yang, M.J.; Pan, Y.Z.; Bai, H. Molecular Mechanism of CRBN in the Activity of Lenalidomide against Myeloma. Zhongguo Shi Yan Xue Ye Xue Za Zhi 2018, 26, 1240–1243. [Google Scholar] [CrossRef]
- Munker, R.; Liu, C.G.; Taccioli, C.; Alder, H.; Heerema, N. MicroRNA profiles of drug-resistant myeloma cell lines. Acta Haematol. 2010, 123, 201–204. [Google Scholar] [CrossRef] [Green Version]
- Vallabhapurapu, S.D.; Noothi, S.K.; Pullum, D.A.; Lawrie, C.H.; Pallapati, R.; Potluri, V.; Kuntzen, C.; Khan, S.; Plas, D.R.; Orlowski, R.Z.; et al. Transcriptional repression by the HDAC4-RelB-p52 complex regulates multiple myeloma survival and growth. Nat. Commun. 2015, 6, 8428. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, L.; Pan, L.; Xiang, B.; Zhu, H.; Wu, Y.; Chen, M.; Guan, P.; Zou, X.; Valencia, C.A.; Dong, B.; et al. Potential role of exosome associated microRNA panels and in vivo environment to predict drug resistance for patients with multiple myeloma. Oncotarget 2016, 7, 30876–30891. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shen, X.; Guo, Y.; Yu, J.; Qi, J.; Shi, W.; Wu, X.; Ni, H.; Ju, S. miRNA-202 in bone marrow stromal cells affects the growth and adhesion of multiple myeloma cells by regulating B cell-activating factor. Clin. Exp Med. 2016, 16, 307–316. [Google Scholar] [CrossRef]
- Hu, W.; Chan, C.S.; Wu, R.; Zhang, C.; Sun, Y.; Song, J.S.; Tang, L.H.; Levine, A.J.; Feng, Z. Negative regulation of tumor suppressor p53 by microRNA miR-504. Mol. Cell 2010, 38, 689–699. [Google Scholar] [CrossRef] [Green Version]
- Bai, H.; Wei, J.; Deng, C.; Yang, X.; Wang, C.; Xu, R. MicroRNA-21 regulates the sensitivity of diffuse large B-cell lymphoma cells to the CHOP chemotherapy regimen. Int. J. Hematol. 2013, 97, 223–231. [Google Scholar] [CrossRef]
- Sun, Y.; Jiang, T.; Jia, Y.; Zou, J.; Wang, X.; Gu, W. LncRNA MALAT1/miR-181a-5p affects the proliferation and adhesion of myeloma cells via regulation of Hippo-YAP signaling pathway. Cell Cycle 2019, 18, 2509–2523. [Google Scholar] [CrossRef] [PubMed]
- Manier, S.; Liu, C.-J.; Avet-Loiseau, H.; Park, J.; Shi, J.; Campigotto, F.; Salem, K.Z.; Huynh, D.; Glavey, S.V.; Rivotto, B.; et al. Prognostic role of circulating exosomal miRNAs in multiple myeloma. Blood 2017, 129, 2429–2436. [Google Scholar] [CrossRef]
- Amodio, N.; Di Martino, M.T.; Foresta, U.; Leone, E.; Lionetti, M.; Leotta, M.; Gulla, A.M.; Pitari, M.R.; Conforti, F.; Rossi, M.; et al. miR-29b sensitizes multiple myeloma cells to bortezomib-induced apoptosis through the activation of a feedback loop with the transcription factor Sp1. Cell Death Dis. 2012, 3, e436. [Google Scholar] [CrossRef] [Green Version]
- Abdi, J.; Rastgoo, N.; Chen, Y.; Chen, G.A.; Chang, H. Ectopic expression of BIRC5-targeting miR-101-3p overcomes bone marrow stroma-mediated drug resistance in multiple myeloma cells. BMC Cancer 2019, 19, 975. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rastgoo, N.; Wu, J.; Liu, M.; Pourabdollah, M.; Atenafu, E.G.; Reece, D.; Chen, W.; Chang, H. Targeting CD47/TNFAIP8 by miR-155 overcomes drug resistance and inhibits tumor growth through induction of phagocytosis and apoptosis in multiple myeloma. Haematologica 2020, 105, 2813–2823. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, Z.; Liang, X.; Wu, W.; Chen, X.; Zeng, Q.; Yang, M.; Ge, J.; Xia, R. Mechanisms underlying the increased chemosensitivity of bortezomib-resistant multiple myeloma by silencing nuclear transcription factor Snail1. Oncol. Rep. 2019, 41, 415–426. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lionetti, M.; Musto, P.; Di Martino, M.T.; Fabris, S.; Agnelli, L.; Todoerti, K.; Tuana, G.; Mosca, L.; Gallo Cantafio, M.E.; Grieco, V.; et al. Biological and clinical relevance of miRNA expression signatures in primary plasma cell leukemia. Clin. Cancer Res. 2013, 19, 3130–3142. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, R.; Tang, S.; Wang, M.; Xu, X.; Yao, C.; Wang, S. MicroRNA-497 induces apoptosis and suppresses proliferation via the Bcl-2/Bax-Caspase9-Caspase3 pathway and cyclin D2 protein in HUVECs. PLoS ONE 2016, 11, e0167052. [Google Scholar]
- Zhu, W.; Zhu, D.; Lu, S.; Wang, T.; Wang, J.; Jiang, B.; Shu, Y.; Liu, P. miR-497 modulates multidrug resistance of human cancer cell lines by targeting BCL2. Med. Oncol. 2012, 29, 384–391. [Google Scholar] [CrossRef] [PubMed]
- Shen, L.; Li, J.; Xu, L.; Ma, J.; Li, H.; Xiao, X.; Zhao, J.; Fang, L. miR-497 induces apoptosis of breast cancer cells by targeting Bcl-w. Exp. Ther. Med. 2012, 3, 475–480. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yadav, S.; Pandey, A.; Shukla, A.; Talwelkar, S.S.; Kumar, A.; Pant, A.B.; Parmar, D. miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2. J. Biol. Chem. 2011, 286, 37347–37357. [Google Scholar] [CrossRef] [Green Version]
- Li, M.; Lee, K.F.; Lu, Y.; Clarke, I.; Shih, D.; Eberhart, C.; Collins, V.P.; Van Meter, T.; Picard, D.; Zhou, L.; et al. Frequent amplification of a chr19q13.41 microRNA polycistron in aggressive primitive neuroectodermal brain tumors. Cancer Cell. 2009, 16, 533–546. [Google Scholar] [CrossRef] [Green Version]
- Robak, P.; Dróżdż, I.; Jarych, D.; Mikulski, D.; Węgłowska, E.; Siemieniuk-Ryś, M.; Misiewicz, M.; Stawiski, K.; Fendler, W.; Szemraj, J.; et al. The Value of Serum MicroRNA Expression Signature in Predicting Refractoriness to Bortezomib-Based Therapy in Multiple Myeloma Patients. Cancers (Basel) 2020, 12, 2569. [Google Scholar] [CrossRef]
- Liu, S.; Zhang, Y.; Huang, C.; Lin, S. miR-215-5p is an anticancer gene in multiple myeloma by targeting RUNX1 and deactivating the PI3K/AKT/mTOR pathway. J. Cell. Biochem 2019, 121, 1475–1490. [Google Scholar] [CrossRef]
- Palagani, A.; Op De Beeck, K.; Naulaerts, S.; Diddens, J.; Sekhar Chirumamilla, C.; Van Camp, G.; Laukens, K.; Heyninck, K.; Gerlo, S.; Mestdagh, P.; et al. Ectopic microRNA-150-5p transcription sensitizes glucocorticoid therapy response in MM1S multiple myeloma cells but fails to overcome hormone therapy resistance in MM1R cells. PLoS ONE 2014, 9, e113842. [Google Scholar] [CrossRef]
- Di Martino, M.T.; Gullà, A.; Cantafio, M.E.; Lionetti, M.; Leone, E.; Amodio, N.; Guzzi, P.H.; Foresta, U.; Conforti, F.; Cannataro, M.; et al. In vitro and in vivo anti-tumor activity of miR-221/222 inhibitors in multiple myeloma. Oncotarget 2013, 4, 242–255. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gullà, A.; Di Martino, M.T.; Gallo Cantafio, M.E.; Morelli, E.; Amodio, N.; Botta, C.; Pitari, M.R.; Lio, S.G.; Britti, D.; Stamato, M.A.; et al. A 13 mer LNA-i-miR-221 inhibitor restores drug sensitivity in melphalan-refractory multiple myeloma cells. Clin. Cancer Res. 2016, 22, 1222–1233. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hao, M.; Zhang, L.; An, G.; Meng, H.; Han, Y.; Xie, Z.; Xu, Y.; Li, C.; Yu, Z.; Chang, H.; et al. Bone marrow stromal cells protect myeloma cells from bortezomib induced apoptosis by suppressing microRNA-15a expression. Leuk. Lymphoma 2011, 52, 1787–1794. [Google Scholar] [CrossRef]
- Keats, J.J.; Chesi, M.; Egan, J.B.; Garbitt, V.M.; Palmer, S.E.; Braggio, E.; Van Wier, S.; Blackburn, P.R.; Baker, A.S.; Dispenzieri, A.; et al. Clonal competition with alternating dominance in multiple myeloma. Blood 2012, 120, 1067–1076. [Google Scholar] [CrossRef] [PubMed]
- Palumbo, A.; Anderson, K. Multiple myeloma. N. Engl. J. Med. 2011, 364, 1046–1060. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Meads, M.B.; Gatenby, R.A.; Dalton, W.S. Environment-mediated drug resistance: A major contributor to minimal residual disease. Nat. Rev. Cancer 2009, 9, 665–674. [Google Scholar] [CrossRef] [PubMed]
- Kang, W.; Tong, J.H.; Lung, R.W.; Dong, Y.; Zhao, J.; Liang, Q.; Zhang, L.; Pan, Y.; Yang, W.; Pang, J.C.; et al. Targeting of YAP1 by microRNA-15a and microRNA-16-1 exerts tumor suppressor function in gastric adenocarcinoma. Mol. Cancer 2015, 14, 52. [Google Scholar] [CrossRef] [Green Version]
- Huang, E.; Liu, R.; Chu, Y. miRNA-15a/16: As tumor suppressors and more. Future Oncol. 2015, 11, 2351–2363. [Google Scholar] [CrossRef]
- Sun, C.Y.; She, X.M.; Qin, Y.; Chu, Z.B.; Chen, L.; Ai, L.S.; Zhang, L.; Hu, Y. miR-15a and miR-16 affect the angiogenesis of multiple myeloma by targeting VEGF. Carcinogenesis 2013, 34, 426–435. [Google Scholar] [CrossRef] [Green Version]
- Li, F.; Xu, Y.; Deng, S.; Li, Z.; Zou, D.; Yi, S.; Sui, W.; Hao, M.; Qiu, L. MicroRNA-15a/16-1 cluster located at chromosome 13q14 is down-regulated but displays different expression pattern and prognostic significance in multiple myeloma. Oncotarget 2015, 6, 38270–38282. [Google Scholar] [CrossRef]
- Faict, S.; Muller, J.; De Veirman, K.; De Bruyne, E. Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts. Blood Cancer J. 2018, 8, 105. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Shen, X.; Guo, Y.; Qi, J.; Shi, W.; Wu, X.; Ni, H.; Ju, S. Study on the association between miRNA-202 expression and drug sensitivity in multiple myeloma cells. Pathol. Oncol. Res. 2016, 22, 531–539. [Google Scholar] [CrossRef]
- Fragioudaki, M.; Boula, A.; Tsirakis, G.; Psarakis, F.; Spanoudakis, M.; Papadakis, I.S.; Pappa, C.A.; Alexandrakis, M.G. B cell-activating factor: Its clinical significance in multiple myeloma patients. Ann. Hematol. 2012, 91, 1413–1418. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Geng, L.; Talmon, G.; Wang, J. MicroRNA-520g confers drug resistance by regulating p21 expression in colorectal cancer. J. Biol. Chem. 2015, 290, 6215–6225. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gregorová, J.; Vrábel, D.; Radová, L.A.; Gablo, N.; Almaši, M.; Štork, M.; Slabý, O.; Pour, L.; Minarík, J.; Ševcíková, S. MicroRNA analysis for extramedullary multiple myeloma relapse. Klin. Onkol. 2018, 31, 148–150. [Google Scholar] [PubMed]
- Rukov, J.L.; Wilentzik, R.; Jaffe, I.; Vinther, J.; Shomron, N. Pharmaco-miR: Linking microRNAs and drug effects. Brief Bioinform. 2014, 15, 648–659. [Google Scholar] [CrossRef] [PubMed]
- Tiberio, P.; Callari, M.; Angeloni, V.; Daidone, M.G.; Appierto, V. Challenges in using circulating miRNAs as cancer biomarkers. Biomed. Res. Int. 2015, 2015, 731479. [Google Scholar] [CrossRef]
- Cheng, H.H.; Yi, H.S.; Kim, Y.; Kroh, E.M.; Chien, J.W.; Eaton, K.D.; Goodman, M.T.; Tait, J.F.; Tewari, M.; Pritchard, C.C. Plasma processing conditions substantially influence circulating microRNA biomarker levels. PLoS ONE 2013, 8, e64795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, R.; Jiang, T.; Kang, X. Circulating microRNAs in cancer: Origin, function and application. J. Exp. Clin. Cancer Res. 2012, 31, 38. [Google Scholar] [CrossRef] [Green Version]
- Turchinovich, A.; Weiz, L.; Burwinkel, B. Extracellular miRNAs: The mystery of their origin and function. Trends Biochem. Sci. 2012, 37, 460–465. [Google Scholar] [CrossRef] [PubMed]
- Wang, K.; Yuan, Y.; Cho, J.H.; McClarty, S.; Baxter, D.; Galas, D.J. Comparing the MicroRNA spectrum between serum and plasma. PLoS ONE 2012, 7, e41561. [Google Scholar] [CrossRef] [PubMed]
- Pritchard, C.C.; Kroh, E.; Wood, B.; Arroyo, J.D.; Dougherty, K.J.; Miyaji, M.M.; Tait, J.F.; Tewari, M. Blood cell origin of circulating microRNAs: A cautionary note for cancer biomarker studies. Cancer Prev. Res. (Phila) 2012, 5, 492–497. [Google Scholar] [CrossRef] [Green Version]
- Sun, Z.; Shi, K.; Yang, S.; Liu, J.; Zhou, Q.; Wang, G.; Song, J.; Li, Z.; Zhang, Z.; Yuan, W. Effect of exosomal miRNA on cancer biology and clinical applications. Mol. Cancer 2018, 17, 147. [Google Scholar] [CrossRef] [PubMed]
- Cheng, L.; Sharples, R.A.; Scicluna, B.J.; Hill, A.F. Exosomes provide a protective and enriched source of miRNA for biomarker profiling compared to intracellular and cell-free blood. J. Extracell. Vesicles 2014, 3, 23743. [Google Scholar] [CrossRef]
- Zhang, X.; Yuan, X.; Shi, H.; Wu, L.; Qian, H.; Xu, W. Exosomes in cancer: Small particle, big player. J. Hematol. Oncol. 2015, 8, 83. [Google Scholar] [CrossRef] [Green Version]
- Saitoh, Y.; Umezu, T.; Imanishi, S.; Asano, M.; Yoshizawa, S.; Katagiri, S.; Suguro, T.; Fujimoto, H.; Akahane, D.; Kobayashi-Kawana, C.; et al. Downregulation of extracellular vesicle microRNA-101 derived from bone marrow mesenchymal stromal cells in myelodysplastic syndrome with disease progression. Oncol. Lett. 2020, 19, 2053–2061. [Google Scholar] [CrossRef]
- Moloudizargari, M.; Abdollahi, M.; Asghari, M.H.; Zimta, A.A.; Neagoe, I.B.; Nabavi, S.M. The emerging role of exosomes in multiple myeloma. Blood Rev. 2019, 38, 100595. [Google Scholar] [CrossRef]
- Colombo, M.; Giannandrea, D.; Lesma, E.; Basile, A.; Chiaramonte, R. Extracellular vesicles enhance multiple myeloma metastatic dissemination. Int. J. Mol. Sci. 2019, 20, 3236. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; De Veirman, K.; Faict, S.; Frassanito, M.A.; Ribatti, D.; Vacca, A.; Menu, E. Multiple myeloma exosomes establish a favourable bone marrow microenvironment with enhanced angiogenesis and immunosuppression. J. Pathol. 2016, 239, 162–173. [Google Scholar] [CrossRef]
- Zarfati, M.; Avivi, I.; Brenner, B.; Katz, T.; Aharon, A. Extracellular vesicles of multiple myeloma cells utilize the proteasome inhibitor mechanism to moderate endothelial angiogenesis. Angiogenesis 2019, 22, 185–196. [Google Scholar] [CrossRef]
- Liu, Y.; Zhu, X.J.; Zeng, C.; Wu, P.H.; Wang, H.X.; Chen, Z.C.; Li, Q.B. Microvesicles secreted from human multiple myeloma cells promote angiogenesis. Acta Pharm. Sin. 2014, 35, 230–238. [Google Scholar] [CrossRef] [Green Version]
- Li, B.; Hong, J.; Hong, M.; Wang, Y.; Yu, T.; Zang, S.; Wu, Q. Pirna-823 delivered by multiple myeloma-derived extracellular vesicles promoted tumorigenesis through re-educating endothelial cells in the tumor environment. Oncogene 2019, 38, 5227–5238. [Google Scholar] [CrossRef]
- Arendt, B.K.; Walters, D.K.; Wu, X.; Tschumper, R.C.; Jelinek, D.F. Multiple myeloma dell-derived microvesicles are enriched in cd147 expression and enhance tumor cell proliferation. Oncotarget 2014, 5, 5686–5699. [Google Scholar] [CrossRef] [Green Version]
- Wang, J.; De Veirman, K.; De Beule, N.; Maes, K.; De Bruyne, E.; Van Valckenborgh, E.; Vanderkerken, K.; Menu, E. The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells. Oncotarget 2015, 6, 43992–44004. [Google Scholar] [CrossRef] [Green Version]
- Pourhanifeh, M.H.; Mahjoubin-Tehran, M.; Shafiee, A.; Hajighadimi, S.; Moradizarmehri, S.; Mirzaei, H.; Asemi, Z. Micrornas and exosomes: Small molecules with big actions in multiple myeloma pathogenesis. Iubmb Life 2020, 72, 314–333. [Google Scholar] [CrossRef] [PubMed]
- Raimondo, S.; Urzì, O.; Conigliaro, A.; Bosco, G.L.; Parisi, S.; Carlisi, M.; Siragusa, S.; Raimondi, L.; Luca, A.; Giavaresi, G.; et al. Extracellular Vesicle microRNAs Contribute to the Osteogenic Inhibition of Mesenchymal Stem Cells in Multiple Myeloma. Cancers (Basel) 2020, 12, 449. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ohyashiki, J.H.; Umezu, T.; Ohyashiki, K. Extracellular vesicle-mediated cell-cell communication in haematological neoplasms. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2018, 373, 20160484. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, J.; Hendrix, A.; Hernot, S.; Lemaire, M.; De Bruyne, E.; Van Valckenborgh, E.; Lahoutte, T.; De Wever, O.; Vanderkerken, K.; Menu, E. Bone marrow stromal cell-derived exosomes as communicators in drug resistance in multiple myeloma cells. Blood 2014, 124, 555–566. [Google Scholar] [CrossRef] [Green Version]
- Rodrigues-Junior, D.M.; Pelarin, M.F.A.; Nader, H.B.; Vettore, A.L.; Pinhal, M.A.S. MicroRNA-1252-5p Associated with Extracellular Vesicles Enhances Bortezomib Sensitivity in Multiple Myeloma Cells by Targeting Heparanase. OncoTargets Ther. 2021, 14, 455–467. [Google Scholar] [CrossRef]
- Janakiraman, H.; House, R.P.; Gangaraju, V.K.; Diehl, J.A.; Howe, P.H.; Palanisamy, V. The long (lncRNA) and short (miRNA) of it: TGFβ- mediated control of RNA-binding proteins and noncoding RNAs. Mol. Cancer Res. 2018, 16, 567–579. [Google Scholar] [CrossRef] [Green Version]
- Allegra, A.; Mania, M.; D’Ascola, A.; Oteri, G.; Siniscalchi, E.N.; Avenoso, A.; Innao, V.; Scuruchi, M.; Allegra, A.G.; Musolino, C.; et al. Altered Long Noncoding RNA Expression Profile in Multiple Myeloma Patients with Bisphosphonate-Induced Osteonecrosis of the Jaw. Biomed. Res. Int. 2020, 2, 9879876. [Google Scholar] [CrossRef]
- Pan, Y.; Zhang, Y.; Liu, W.; Huang, Y.; Shen, X.; Jing, R.; Pu, J.; Wang, X.; Ju, S.; Cong, H.; et al. LncRNA H19 overexpression induces bortezomib resistance in multiple myeloma by targeting MCL-1 via miR-29b-3p. Cell Death Dis. 2019, 10, 106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Di Martino, M.T.; Guzzi, P.H.; Caracciolo, D.; Agnelli, L.; Neri, A.; Walker, B.A.; Morgan, G.J.; Cannataro, M.; Tassone, P.; Tagliaferri, P. Integrated analysis of microRNAs, transcription factors and target genes expression discloses a specific molecular architecture of hyperdiploid multiple myeloma. Oncotarget 2015, 6, 19132–19147. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Allegra, A.; Penna, G.; Alonci, A.; Rizzo, V.; Russo, S.; Musolino, C. Nanoparticles in oncology: The new theragnostic molecules. Anticancer Agents Med. Chem. 2011, 11, 669–686. [Google Scholar] [CrossRef] [PubMed]
- Cheng, C.J.; Bahal, R.; Babar, I.A.; Pincus, Z.; Barrera, F.; Liu, C.; Svoronos, A.; Braddock, D.T.; Glazer, P.M.; Engelman, D.M.; et al. MicroRNA silencing for cancer therapy targeted to the tumour microenvironment. Nature 2015, 518, 107–110. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, X.; Chen, Y.; Li, H.; Huang, N.; Jin, Q.; Ren, K.; Ji, J. Enhanced retention and cellular uptake of nanoparticles in tumors by controlling their aggregation behavior. ACS Nano 2013, 7, 6244–6257. [Google Scholar] [CrossRef] [PubMed]
- Gallo Cantafio, M.E.; Nielsen, B.S.; Mignogna, C.; Arbitrio, M.; Botta, C.; Frandsen, N.M.; Rolfo, C.; Tagliaferri, P.; Tassone, P.; Di Martino, M.T. Pharmacokinetics and Pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in Mice and Non-human Primates. Mol. Ther. Nucleic Acids. 2016, 21, 5. [Google Scholar] [CrossRef] [Green Version]
- Abdi, J.; Jian, H.; Chang, H. Role of micro-RNAs in drug resistance of multiple myeloma. Oncotarget 2016, 7, 60723–60735. [Google Scholar] [CrossRef] [Green Version]
- Li, M.P.; Hu, Y.D.; Hu, X.L.; Zhang, Y.J.; Yang, Y.L.; Jiang, C.; Tang, J.; Chen, X.P. MiRNAs and miRNA Polymorphisms Modify Drug Response. Int. J. Env. Res. Public Health 2016, 13, 1096. [Google Scholar] [CrossRef] [Green Version]
- Meads, M.B.; Hazlehurst, L.A.; Dalton, W.S. The bone marrow microenvironment as a tumor sanctuary and contributor to drug resistance. Clin. Cancer Res. 2008, 14, 2519–2526. [Google Scholar] [CrossRef] [Green Version]
- Li, Z.W.; Dalton, W.S. Tumor microenvironment and drug resistance in hematologic malignancies. Blood Rev. 2006, 20, 333–342. [Google Scholar] [CrossRef]
- Innao, V.; Allegra, A.; Pulvirenti, N.; Allegra, A.G.; Musolino, C. Therapeutic potential of antagomiRs in haematological and oncological neoplasms. Eur. J. Cancer Care (Engl.) 2020, 29, e13208. [Google Scholar] [CrossRef]
- Van Rooij, E.; Marshall, W.S.; Olson, E.N. Toward microrna–based therapeutics for heart disease: The sense in antisense. Circ. Res. 2008, 103, 919–928. [Google Scholar] [CrossRef] [PubMed]
- Vester, B.; Wengel, J. LNA (locked nucleic acid): High-affinity targeting of complementary RNA and DNA. Biochemistry 2004, 43, 13233–13241. [Google Scholar] [CrossRef]
- Ebert, M.S.; Neilson, J.R.; Shapr, P.A. MicroRNA sponges: Competitive inhibitors of small RNAs in mammalian cells. Nat. Methods 2007, 4, 721–726. [Google Scholar] [CrossRef] [PubMed]
- Choi, W.Y.; Giraldez, A.J.; Schier, A.F. Target protectors reveal dampening and balancing of Nodal agonist and antagonist by miR-430. Science 2007, 318, 271–274. [Google Scholar] [CrossRef]
Drug-Resistance | Type of miRNAs | Action | Target Cells | Effect | Reference |
---|---|---|---|---|---|
Dexamethasone | miRNA-221 | increased | MM1R | BAX/Bak1 | [65] |
miRNA-222 | increased | MM1R | BAX/Bak1 | [65] | |
miRNA-15a | decreased | MM1R | ↑IL-6 | [66] | |
miRNA-16 | decreased | MM1R | ↑IL-6 | [66] | |
miRNA-21 | increased | KMS-26, U-266, OPM-2, INA-6 | RhoB | [67] | |
miRNA-125b | increased | MM1S | Bak1/SIRT1 and↓p53 | [68] | |
miRNA-182 | increased | H929, MM.1S | FOXO3A | [69,70] | |
IMiDs | AGO2 | increased | IMiD-sensitive MM cells | cereblon | [71,72] |
Alkylants | miRNA-221 | Increased | RPMI8226/Dox6 and RPMI8226/LR5, U266Dox and U266/LR7 | ↑PUMA, SL7A5/LAT1, ABCC1/MRP1, BAX/Bak1, RelB-p52 | [73,74] |
miRNA-222 | Increased | RPMI8226/Dox6 and RPMI8226/LR5, U266Dox and U266/LR7 | ↑PUMA, SL7A5/LAT1, ABCC1/MRP1, BAX/Bak1 | [73,74] | |
Bortezomib | miRNA-21 | Increased | RhoB, NFkB | [67] | |
miRNA-15a-5p | Decreased | BTZ-resistant cells | MAP-k, E2 enzymes | [75] | |
miRNA-16-5p | Decreased | BTZ-resistant cells | MAP-k, E2 enzymes | [75] | |
miRNA-17-5p | Decreased | BTZ-resistant cells | MAP-k, E2 enzymes | [75] | |
miRNA-20a-5p | Decreased | BTZ-resistant cells | MAP-k, E2 enzymes | [75] | |
miRNA-125b-5p | Decreased | BTZ-resistant cell | MAP-k, E2 enzymes | [76] | |
miRNA-21-5p | Decreased | U266, | MAP-k, E2 enzymes | [40,77,78] | |
miRNA-181a-5p | Increased | U266, MM.1S, RPMI8226 | cell growth and MM cells adhesion | [79] | |
miRNA-376c-3p | Increased | U266, MM.1S, RPMI8226 | unknown | [79] | |
miRNA-215-5p | Increased | U266, MM.1S, RPMI8226 | unknown | [79] | |
miRNA-18a | Increased | Primary MM cells | ↓HIF-1α | [80] | |
let-7b | Increased | Primary MM cells | ↑oncogenes CCND1, MYC, RAS | [80] | |
miRNA-29b | Decreased | Primary MM cells | ↑oncogene SP-1 | [81] | |
miRNA-27a-5p | Decreased | Primary MM cells | ↑oncogene SP-1 | [81] | |
miRNA-202 | Decreased | U266 | ↑oncogene BAFF, JNK/SAPK, BAX | [76] | |
miRNA-101-3p | Decreased | RPMI-8226, U266, MM.1S, OPM2, HS-5 | ↑survivin (BIRC5) | [82] | |
miRNA-155 | Decreased | Primary MM cells, MM1R | ↑CD47, ↑TNF1IP8 | [38,83] | |
miRNA-22-3p | Increased | MM cells | ↑Snail1/hsa, ↓p53 | [84] | |
miRNA-497 | decreased | Primary plasma cell leukemia cells | Bcl-2 | [85,86,87,88,89,90] | |
miRNA-520g/h | decreased | BTZ-resistant MM cells | Rad51, APE1 | [40] | |
miRNA-16-2-3p | increased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-19b-3p | increased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-30e-5p | increased | Cells from BTZ-refractory subjects | multiple | [91,92] | |
miRNA-122-5p | increased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-143-3p | increased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-148a-3p | increased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-215-5p | increased | Cells from BTZ-refractory subjects | multiple | [91,92] | |
miRNA-30c-5p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-130a-3p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-151a-3p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNa-181a-5p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-191-5p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNa-328-3p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-376a-3p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNa-409-3p | decreased | Cells from BTZ-refractory subjects | Multiple | [91] | |
miRNA-744-5p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
miRNA-1224-3p | decreased | Cells from BTZ-refractory subjects | multiple | [91] | |
Carfilzomib | miRNA-101-3p | decreased | RPMI-8226, U266, MM.1S, OPM2, HS-5 | ↑survivin BIRC5 | [82] |
Doxorubicin | miRNA-21 | increased | BTZ-resistant MM cells | RhoB | [40] |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Allegra, A.; Ettari, R.; Innao, V.; Bitto, A. Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma. Cells 2021, 10, 448. https://doi.org/10.3390/cells10020448
Allegra A, Ettari R, Innao V, Bitto A. Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma. Cells. 2021; 10(2):448. https://doi.org/10.3390/cells10020448
Chicago/Turabian StyleAllegra, Alessandro, Roberta Ettari, Vanessa Innao, and Alessandra Bitto. 2021. "Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma" Cells 10, no. 2: 448. https://doi.org/10.3390/cells10020448
APA StyleAllegra, A., Ettari, R., Innao, V., & Bitto, A. (2021). Potential Role of microRNAs in inducing Drug Resistance in Patients with Multiple Myeloma. Cells, 10(2), 448. https://doi.org/10.3390/cells10020448