International Journal of Molecular Sciences

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12 pages, 5672 KiB

Open AccessArticle

MicroRNAs Targeting Caspase-3 and -7 in PANC-1 Cells

by Jong Kook Park, Andrea I. Doseff and Thomas D. Schmittgen

Int. J. Mol. Sci. 2018, 19(4), 1206; https://doi.org/10.3390/ijms19041206 - 16 Apr 2018

Cited by 29 | Viewed by 9253

Abstract

MicroRNAs (miRNAs), a critical part of the RNA silencing machinery, are known to play important regulatory roles in cancer. However, the consequence of miRNA deregulation in cancer is unknown for many miRNAs. Here, we define that miRNAs, miR-17-5p, miR-132-3p/-212-3p, and miR-337-3p are significantly [...] Read more.

MicroRNAs (miRNAs), a critical part of the RNA silencing machinery, are known to play important regulatory roles in cancer. However, the consequence of miRNA deregulation in cancer is unknown for many miRNAs. Here, we define that miRNAs, miR-17-5p, miR-132-3p/-212-3p, and miR-337-3p are significantly up-regulated in the pancreatic ductal adenocarcinomas (PDAC) compared to the normal and benign tissues. Furthermore, by using PANC-1 cells, we demonstrate that overexpressed miR-337-3p and miR-17-5p/miR-132-3p/-212-3p can regulate executioner caspases-3 and -7, respectively. In addition, over-expression of miRNAs, especially miR-337-3p, attenuates tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) cytotoxicity in PANC-1 cells. Our findings unveil an important biological function for miRNAs up-regulated in PDAC in coordinately regulating caspases, potentially contributing to the malignant progression of PDAC. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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13 pages, 2719 KiB

Open AccessArticle

A Comprehensive Analysis of Argonaute-CLIP Data Identifies Novel, Conserved and Species-Specific Targets of miR-21 in Human Liver and Hepatocellular Carcinoma

by Aaron Balasingam Koenig, Juan Martín Barajas, María Jose Guerrero and Kalpana Ghoshal

Int. J. Mol. Sci. 2018, 19(3), 851; https://doi.org/10.3390/ijms19030851 - 14 Mar 2018

Cited by 28 | Viewed by 4950

Abstract

MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as cross-linking and immunoprecipitation [...] Read more.

MicroRNAs are ~22 nucleotide RNAs that regulate gene expression at the post-transcriptional level by binding messenger RNA transcripts. miR-21 is described as an oncomiR whose steady-state levels are commonly increased in many malignancies, including hepatocellular carcinoma (HCC). Methods known as cross-linking and immunoprecipitation of RNA followed by sequencing (CLIP-seq) have enabled transcriptome-wide identification of miRNA interactomes. In our study, we use a publicly available Argonaute-CLIP dataset (GSE97061), which contains nine HCC cases with matched benign livers, to characterize the miR-21 interactome in HCC. Argonaute-CLIP identified 580 miR-21 bound target sites on coding transcripts, of which 332 were located in the coding sequences, 214 in the 3′-untranslated region, and 34 in the 5′-untranslated region, introns, or downstream sequences. We compared the expression of miR-21 targets in 377 patients with liver cancer from the data generated by The Cancer Genome Atlas (TCGA) and found that mRNA levels of 402 miR-21 targets are altered in HCC. Expression of three novel predicted miR-21 targets (CAMSAP1, DDX1 and MARCKSL1) correlated with HCC patient survival. Analysis of RNA-seq data from SK-Hep1 cells treated with a miR-21 antisense oligonucleotide (GSE65892) identified RMND5A, an E3 ubiquitin ligase, as a strong miR-21 candidate target. Collectively, our analysis identified novel miR-21 targets that are likely to play a causal role in hepatocarcinogenesis. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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19 pages, 2870 KiB

Open AccessArticle

Luminal lncRNAs Regulation by ERα-Controlled Enhancers in a Ligand-Independent Manner in Breast Cancer Cells

by Valentina Miano, Giulio Ferrero, Valentina Rosti, Eleonora Manitta, Jamal Elhasnaoui, Giulia Basile and Michele De Bortoli

Int. J. Mol. Sci. 2018, 19(2), 593; https://doi.org/10.3390/ijms19020593 - 16 Feb 2018

Cited by 13 | Viewed by 5514

Abstract

Estrogen receptor-α (ERα) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ERα (apoERα) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, [...] Read more.

Estrogen receptor-α (ERα) is a ligand-inducible protein which mediates estrogenic hormones signaling and defines the luminal BC phenotype. Recently, we demonstrated that even in absence of ligands ERα (apoERα) binds chromatin sites where it regulates transcription of several protein-coding and lncRNA genes. Noteworthy, apoERα-regulated lncRNAs marginally overlap estrogen-induced transcripts, thus representing a new signature of luminal BC genes. By the analysis of H3K27ac enrichment in hormone-deprived MCF-7 cells, we defined a set of Super Enhancers (SEs) occupied by apoERα, including one mapped in proximity of the DSCAM-AS1 lncRNA gene. This represents a paradigm of apoERα activity since its expression is largely unaffected by estrogenic treatment, despite the fact that E2 increases ERα binding on DSCAM-AS1 promoter. We validated the enrichment of apoERα, p300, GATA3, FoxM1 and CTCF at both DSCAM-AS1 TSS and at its associated SE by ChIP-qPCR. Furthermore, by analyzing MCF-7 ChIA-PET data and by 3C assays, we confirmed long range chromatin interaction between the SE and the DSCAM-AS1 TSS. Interestingly, CTCF and p300 binding showed an enrichment in hormone-depleted medium and in the presence of ERα, elucidating the dynamics of the estrogen-independent regulation of DSCAM-AS1 expression. The analysis of this lncRNA provides a paradigm of transcriptional regulation of a luminal specific apoERα regulated lncRNA. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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15 pages, 3465 KiB

Open AccessArticle

Complex Epigenetic Regulation of Chemotherapy Resistance and Biology in Esophageal Squamous Cell Carcinoma via MicroRNAs

by Kirsten Lindner, Ann-Kathrin Eichelmann, Christiane Matuszcak, Damian James Hussey, Jörg Haier and Richard Hummel

Int. J. Mol. Sci. 2018, 19(2), 499; https://doi.org/10.3390/ijms19020499 - 7 Feb 2018

Cited by 25 | Viewed by 4545 | Correction

Abstract

Background: Resistance towards chemotherapy is a major obstacle in the treatment of esophageal squamous cell carcinoma (ESCC). We investigated the role of specific microRNAs in chemotherapy resistance and tumor biology. Methods: We selected three microRNAs from characteristic microRNA signatures of resistant ESCC (hsa-miR-125a-5p, [...] Read more.

Background: Resistance towards chemotherapy is a major obstacle in the treatment of esophageal squamous cell carcinoma (ESCC). We investigated the role of specific microRNAs in chemotherapy resistance and tumor biology. Methods: We selected three microRNAs from characteristic microRNA signatures of resistant ESCC (hsa-miR-125a-5p, hsa-miR-130a-3p, hsa-miR-1226-3p), and hsa-miR-148a-3p. Effects on chemotherapy, adhesion, migration, apoptosis and cell cycle were assessed in six ESCC cell lines. Target analyses were performed using Western blotting and luciferase techniques. Results: MiR-130a-3p sensitized cells towards cisplatin in 100% of cell lines, miR-148a-3p in 83%, miR-125a-5p in 67%, miR-1226-3p in 50% (p ≤ 0.04). MiR-130a-3p sensitized 83% of cell lines towards 5-FU, miR-148a-3p/miR-125a-5p/miR-1226-3p only 33% (p ≤ 0.015). Several resistance-relevant pathways seem to be targeted on various levels. Bcl-2 was confirmed as a direct target of miR-130a-3p and miR-148a-3p, and p53 as a target of miR-125a-5p. All microRNAs decreased migration and adhesion, except miR-130a-3p, and increased apoptosis. Simultaneous manipulation of two microRNAs exhibited additive sensitizing effects towards cisplatin in 50% (miR-125a-5p/miR-148a-3p), and 75% (miR-148a-3p/miR-130a-3p) of cell lines (p ≤ 0.006). Conclusion: Our data present strong evidence that specific microRNA signatures are responsible for drug resistance and aggressiveness of ESCC. Final functional readout of these complex processes appears to be more important than single microRNA-target interactions. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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13 pages, 3002 KiB

Open AccessArticle

Corylin Suppresses Hepatocellular Carcinoma Progression via the Inhibition of Epithelial-Mesenchymal Transition, Mediated by Long Noncoding RNA GAS5

by Chi-Yuan Chen, Chin-Chuan Chen, Tzong-Ming Shieh, Chuen Hsueh, Shu-Huei Wang, Yann-Lii Leu, Jang-Hau Lian and Tong-Hong Wang

Int. J. Mol. Sci. 2018, 19(2), 380; https://doi.org/10.3390/ijms19020380 - 27 Jan 2018

Cited by 62 | Viewed by 6108

Abstract

Corylin is a flavonoid extracted from the nuts of Psoralea corylifolia L. (Fabaceae), which is a widely used anti-inflammatory and anticancer herb in China. Recent studies revealed antioxidant, anti-inflammatory, and bone differentiation–promoting effects of corylin. However, there are no studies examining the anticancer [...] Read more.

Corylin is a flavonoid extracted from the nuts of Psoralea corylifolia L. (Fabaceae), which is a widely used anti-inflammatory and anticancer herb in China. Recent studies revealed antioxidant, anti-inflammatory, and bone differentiation–promoting effects of corylin. However, there are no studies examining the anticancer activity of corylin. In this study, we used cells and animal models to examine the antitumor effects of corylin on hepatocellular carcinoma (HCC) and then studied its downstream regulatory mechanisms. The results showed that corylin significantly inhibited the proliferation, migration, and invasiveness of HCC cells and suppressed epithelial–mesenchymal transition. We found that the anti-HCC mechanism of corylin’s action lies in the upregulation of tumor suppressor long noncoding RNA growth arrest-specific transcript 5 (GAS5) and the activation of its downstream anticancer pathways. In animal experiments, we also found that corylin can significantly inhibit tumor growth without significant physiological toxicity. The above results suggest that corylin has anti-HCC effects and good potential as a clinical treatment. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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4632 KiB

Open AccessArticle

Oncomirs Expression Profiling in Uterine Leiomyosarcoma Cells

by Bruna Cristine De Almeida, Natalia Garcia, Giovana Maffazioli, Laura Gonzalez dos Anjos, Edmund Chada Baracat and Katia Candido Carvalho

Int. J. Mol. Sci. 2018, 19(1), 52; https://doi.org/10.3390/ijms19010052 - 25 Dec 2017

Cited by 16 | Viewed by 7339

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. They play a key role in several biological processes. Their abnormal expression may lead to malignant cell transformation. This study aimed to evaluate the expression profile [...] Read more.

MicroRNAs (miRNAs) are small non-coding RNAs that act as regulators of gene expression at the post-transcriptional level. They play a key role in several biological processes. Their abnormal expression may lead to malignant cell transformation. This study aimed to evaluate the expression profile of 84 miRNAs involved in tumorigenesis in immortalized cells of myometrium (MM), uterine leiomyoma (ULM), and uterine leiomyosarcoma (ULMS). Specific cell lines were cultured and qRT-PCR was performed. Thirteen miRNAs presented different expression profiles in ULM and the same thirteen in ULMS compared to MM. Eight miRNAs were overexpressed, and five were underexpressed in ULM. In ULMS cells, five miRNAs exhibited an overexpression and eight were down-regulated. Six miRNAs (miR-1-3p, miR-130b-3p, miR-140-5p, miR-202-3p, miR-205-5p, and miR-7-5p) presented a similar expression pattern in cell lines compared to patient samples. Of these, only three miRNAs showed significant expression in ULM (miR-1-3p, miR-140-5p, and miR-7-5p) and ULMS (miR-1-3p, miR-202-3p, and miR-7-5p). Our preliminary approach identified 24 oncomirs with an altered expression profile in ULM and ULMS cells. We identified four differentially expressed miRNAs with the same profile when compared with patients’ samples, which strongly interacted with relevant genes, including apoptosis regulator (BCL2), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), insulin like growth factor 1 receptor (IGF1R),serine/threonine kinase (RAF1), receptor tyrosine kinase (MET), and bHLH transcription factor (MYCN). This led to alterations in their mRNA-target. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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4021 KiB

Open AccessArticle

Plasma miR-155, miR-203, and miR-205 are Biomarkers for Monitoring of Primary Cutaneous T-Cell Lymphomas

by Nina Dusílková, Petra Bašová, Jindřich Polívka, Ondřej Kodet, Vojtěch Kulvait, Michal Pešta, Marek Trněný and Tomáš Stopka

Int. J. Mol. Sci. 2017, 18(10), 2136; https://doi.org/10.3390/ijms18102136 - 15 Oct 2017

Cited by 34 | Viewed by 7974

Abstract

Primary cutaneous T-cell lymphomas (CTCL) affect the skin and tend to transform and spread. CTCL involves primarily the Mycosis fungoides (MF) and more aggressive Sezary syndrome (SS). Oncogenic microRNAs (miRs) are stable epigenetic inhibitors often deregulated in the tumour and detectable as biomarkers [...] Read more.

Primary cutaneous T-cell lymphomas (CTCL) affect the skin and tend to transform and spread. CTCL involves primarily the Mycosis fungoides (MF) and more aggressive Sezary syndrome (SS). Oncogenic microRNAs (miRs) are stable epigenetic inhibitors often deregulated in the tumour and detectable as biomarkers in non-cellular fractions of peripheral blood. The tumour-specific expression of miR-155, miR-203, and miR-205 was shown to correctly diagnose CTCL. We herein asked whether these microRNAs can be used as plasma biomarkers for clinical CTCL monitoring. Patients with CTCL (n = 10) and controls with non-malignant conditions (n = 11) repeatedly donated plasma samples every ca. five months. MicroRNAs were detected in the plasma samples by specifically-primed RT-PCR followed by multivariate analyses of the miR expression dynamics. We herein established the plasma miR-classifier for detecting CTCL based on the miR-155 upregulation and miR-203/miR-205 downregulation with 100% specificity and 94% sensitivity. The 3-miR-score in the consecutive samples coincided with the clinical outcome of MF and SS patients such as the therapy response or changes in the clinical stage or tumor size. Quantitation of the selected microRNAs in plasma is a specific and straightforward approach for evaluating CTCL outcome representing, thus, a valuable tool for CTCL diagnostics and therapy response monitoring. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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1189 KiB

Open AccessArticle

Prediction Potential of Serum miR-155 and miR-24 for Relapsing Early Breast Cancer

by Petra Bašová, Michal Pešta, Marek Sochor and Tomáš Stopka

Int. J. Mol. Sci. 2017, 18(10), 2116; https://doi.org/10.3390/ijms18102116 - 10 Oct 2017

Cited by 26 | Viewed by 5072

Abstract

Oncogenic microRNAs (oncomiRs) accumulate in serum due to their increased stability and thus serve as biomarkers in breast cancer (BC) pathogenesis. Four oncogenic microRNAs (miR-155, miR-19a, miR-181b, and miR-24) and one tumor suppressor microRNA (let-7a) were shown to differentiate between high- and low-risk [...] Read more.

Oncogenic microRNAs (oncomiRs) accumulate in serum due to their increased stability and thus serve as biomarkers in breast cancer (BC) pathogenesis. Four oncogenic microRNAs (miR-155, miR-19a, miR-181b, and miR-24) and one tumor suppressor microRNA (let-7a) were shown to differentiate between high- and low-risk early breast cancer (EBC) and reflect the surgical tumor removal and adjuvant therapy. Here we applied the longitudinal multivariate data analyses to stochastically model the serum levels of each of the oncomiRs using the RT-PCR measurements in the EBC patients (N = 133) that were followed up 4 years after diagnosis. This study identifies that two of the studied oncomiRs, miR-155 and miR-24, are highly predictive of EBC relapse. Furthermore, combining the oncomiR level with Ki-67 expression further specifies the relapse probability. Our data move further the notion that oncomiRs in serum enable not only monitoring of EBC but also are a very useful tool for predicting relapse independently of any other currently analyzed characteristics in EBC patients. Our approach can be translated into medical practice to estimate individual relapse risk of EBC patients. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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Review

Jump to: Research

26 pages, 2180 KiB

Open AccessReview

Long Non-Coding RNAs Guide the Fine-Tuning of Gene Regulation in B-Cell Development and Malignancy

by Mette Dahl, Lasse Sommer Kristensen and Kirsten Grønbæk

Int. J. Mol. Sci. 2018, 19(9), 2475; https://doi.org/10.3390/ijms19092475 - 21 Aug 2018

Cited by 37 | Viewed by 7328

Abstract

With the introduction of next generation sequencing methods, such as RNA sequencing, it has become apparent that alterations in the non-coding regions of our genome are important in the development of cancer. Particularly interesting is the class of long non-coding RNAs (lncRNAs), including [...] Read more.

With the introduction of next generation sequencing methods, such as RNA sequencing, it has become apparent that alterations in the non-coding regions of our genome are important in the development of cancer. Particularly interesting is the class of long non-coding RNAs (lncRNAs), including the recently described subclass of circular RNAs (circRNAs), which display tissue- and cell-type specific expression patterns and exert diverse regulatory functions in the cells. B-cells undergo complex and tightly regulated processes in order to develop from antigen naïve cells residing in the bone marrow to the highly diverse and competent effector cells circulating in peripheral blood. These processes include V(D)J recombination, rapid proliferation, somatic hypermutation and clonal selection, posing a risk of malignant transformation at each step. The aim of this review is to provide insight into how lncRNAs including circRNAs, participate in normal B-cell differentiation, and how deregulation of these molecules is involved in the development of B-cell malignancies. We describe the prognostic value and functional significance of specific deregulated lncRNAs in diseases such as acute lymphoblastic leukemia, chronic lymphocytic leukemia, mantle cell lymphoma, diffuse large B-cell lymphoma, follicular lymphoma, Burkitt lymphoma and multiple myeloma, and we provide an overview of the current knowledge on the role of circRNAs in these diseases. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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16 pages, 628 KiB

Open AccessReview

Alteration of Epigenetic Regulation by Long Noncoding RNAs in Cancer

by Mariangela Morlando and Alessandro Fatica

Int. J. Mol. Sci. 2018, 19(2), 570; https://doi.org/10.3390/ijms19020570 - 14 Feb 2018

Cited by 141 | Viewed by 10902

Abstract

Long noncoding RNAs (lncRNAs) are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin [...] Read more.

Long noncoding RNAs (lncRNAs) are important regulators of the epigenetic status of the human genome. Besides their participation to normal physiology, lncRNA expression and function have been already associated to many diseases, including cancer. By interacting with epigenetic regulators and by controlling chromatin topology, their misregulation may result in an aberrant regulation of gene expression that may contribute to tumorigenesis. Here, we review the functional role and mechanisms of action of lncRNAs implicated in the aberrant epigenetic regulation that has characterized cancer development and progression. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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25 pages, 657 KiB

Open AccessReview

MicroRNAs as New Biomarkers for Diagnosis and Prognosis, and as Potential Therapeutic Targets in Acute Myeloid Leukemia

by Stefania Trino, Daniela Lamorte, Antonella Caivano, Ilaria Laurenzana, Daniela Tagliaferri, Geppino Falco, Luigi Del Vecchio, Pellegrino Musto and Luciana De Luca

Int. J. Mol. Sci. 2018, 19(2), 460; https://doi.org/10.3390/ijms19020460 - 3 Feb 2018

Cited by 67 | Viewed by 10751

Abstract

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that [...] Read more.

Acute myeloid leukemias (AML) are clonal disorders of hematopoietic progenitor cells which are characterized by relevant heterogeneity in terms of phenotypic, genotypic, and clinical features. Among the genetic aberrations that control disease development there are microRNAs (miRNAs). miRNAs are small non-coding RNAs that regulate, at post-transcriptional level, translation and stability of mRNAs. It is now established that deregulated miRNA expression is a prominent feature in AML. Functional studies have shown that miRNAs play an important role in AML pathogenesis and miRNA expression signatures are associated with chemotherapy response and clinical outcome. In this review we summarized miRNA signature in AML with different cytogenetic, molecular and clinical characteristics. Moreover, we reviewed the miRNA regulatory network in AML pathogenesis and we discussed the potential use of cellular and circulating miRNAs as biomarkers for diagnosis and prognosis and as therapeutic targets. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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28 pages, 1154 KiB

Open AccessReview

Epigenetics and MicroRNAs in Cancer

by Alice Ramassone, Sara Pagotto, Angelo Veronese and Rosa Visone

Int. J. Mol. Sci. 2018, 19(2), 459; https://doi.org/10.3390/ijms19020459 - 3 Feb 2018

Cited by 129 | Viewed by 12094

Abstract

The ability to reprogram the transcriptional circuitry by remodeling the three-dimensional structure of the genome is exploited by cancer cells to promote tumorigenesis. This reprogramming occurs because of hereditable chromatin chemical modifications and the consequent formation of RNA-protein-DNA complexes that represent the principal [...] Read more.

The ability to reprogram the transcriptional circuitry by remodeling the three-dimensional structure of the genome is exploited by cancer cells to promote tumorigenesis. This reprogramming occurs because of hereditable chromatin chemical modifications and the consequent formation of RNA-protein-DNA complexes that represent the principal actors of the epigenetic phenomena. In this regard, the deregulation of a transcribed non-coding RNA may be both cause and consequence of a cancer-related epigenetic alteration. This review summarizes recent findings that implicate microRNAs in the aberrant epigenetic regulation of cancer cells. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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1589 KiB

Open AccessReview

Development of Novel Therapeutic Agents by Inhibition of Oncogenic MicroRNAs

by Dinh-Duc Nguyen and Suhwan Chang

Int. J. Mol. Sci. 2018, 19(1), 65; https://doi.org/10.3390/ijms19010065 - 27 Dec 2017

Cited by 69 | Viewed by 8857

Abstract

MicroRNAs (miRs, miRNAs) are regulatory small noncoding RNAs, with their roles already confirmed to be important for post-transcriptional regulation of gene expression affecting cell physiology and disease development. Upregulation of a cancer-causing miRNA, known as oncogenic miRNA, has been found in many types [...] Read more.

MicroRNAs (miRs, miRNAs) are regulatory small noncoding RNAs, with their roles already confirmed to be important for post-transcriptional regulation of gene expression affecting cell physiology and disease development. Upregulation of a cancer-causing miRNA, known as oncogenic miRNA, has been found in many types of cancers and, therefore, represents a potential new class of targets for therapeutic inhibition. Several strategies have been developed in recent years to inhibit oncogenic miRNAs. Among them is a direct approach that targets mature oncogenic miRNA with an antisense sequence known as antimiR, which could be an oligonucleotide or miRNA sponge. In contrast, an indirect approach is to block the biogenesis of miRNA by genome editing using the CRISPR/Cas9 system or a small molecule inhibitor. The development of these inhibitors is straightforward but involves significant scientific and therapeutic challenges that need to be resolved. In this review, we summarize recent relevant studies on the development of miRNA inhibitors against cancer. Full article

(This article belongs to the Special Issue Non-Coding RNAs and Epigenetics in Cancer & Selected Papers from the 2nd International Symposium on Frontiers in Molecular Science)

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