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13 pages, 2451 KiB

Open AccessArticle

miR-22-3p Negatively Affects Tumor Progression in T-Cell Acute Lymphoblastic Leukemia

by Valentina Saccomani, Angela Grassi, Erich Piovan, Deborah Bongiovanni, Ludovica Di Martino, Sonia Minuzzo, Valeria Tosello and Paola Zanovello

Cells 2020, 9(7), 1726; https://doi.org/10.3390/cells9071726 - 18 Jul 2020

Cited by 17 | Viewed by 3584

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive disease arising from T-cell precursors. NOTCH1 plays an important role both in T-cell development and leukemia progression, and more than 60% of human T-ALLs harbor mutations in components of the NOTCH1 signaling pathway, leading [...] Read more.

T-cell acute lymphoblastic leukemia (T-ALL) is a rare, aggressive disease arising from T-cell precursors. NOTCH1 plays an important role both in T-cell development and leukemia progression, and more than 60% of human T-ALLs harbor mutations in components of the NOTCH1 signaling pathway, leading to deregulated cell growth and contributing to cell transformation. Besides multiple NOTCH1 target genes, microRNAs have also been shown to regulate T-ALL initiation and progression. Using an established mouse model of T-ALL induced by NOTCH1 activation, we identified several microRNAs downstream of NOTCH1 activation. In particular, we found that NOTCH1 inhibition can induce miR-22-3p in NOTCH1-dependent tumors and that this regulation is also conserved in human samples. Importantly, miR-22-3p overexpression in T-ALL cells can inhibit colony formation in vitro and leukemia progression in vivo. In addition, miR-22-3p was found to be downregulated in T-ALL specimens, both T-ALL cell lines and primary samples, relative to immature T-cells. Our results suggest that miR-22-3p is a functionally relevant microRNA in T-ALL whose modulation can be exploited for therapeutic purposes to inhibit T-ALL progression. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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16 pages, 3218 KiB

Open AccessFeature PaperArticle

Let-7 miRNA’s Expression Profile and Its Potential Prognostic Role in Uterine Leiomyosarcoma

by Bruna Cristine de Almeida, Laura Gonzalez dos Anjos, Miyuki Uno, Isabela Werneck da Cunha, Fernando Augusto Soares, Glauco Baiocchi, Edmund Chada Baracat and Katia Candido Carvalho

Cells 2019, 8(11), 1452; https://doi.org/10.3390/cells8111452 - 17 Nov 2019

Cited by 20 | Viewed by 3429

Abstract

The lethal-7 (let-7) family is an important microRNA (miRNA) group that usually exerts functions as a tumor suppressor. We aimed to evaluate the expression profile of let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i and to assess their value as prognostic [...] Read more.

The lethal-7 (let-7) family is an important microRNA (miRNA) group that usually exerts functions as a tumor suppressor. We aimed to evaluate the expression profile of let-7a, let-7b, let-7c, let-7d, let-7e, let-7f, let-7g, and let-7i and to assess their value as prognostic markers in uterine leiomyosarcoma (LMS) patients. The miRNAs expression profile was assessed in 34 LMS and 13 normal myometrium (MM) paraffin-embedded samples. All let-7 family members showed downregulation in LMS. Our findings showed that patients with let-7e downregulation had worse overall survival (OS) and is an independent prognostic factor (hazard ratio [HR] = 2.24). In addition, almost half the patients had distant metastasis. LMS patients with downregulated let-7b and let-7d had worse disease-free survival (DFS); they are not independent prognostic factors (HR = 2.65). Patients’ ages were associated with let-7d, let-7e and let-7f (p = 0.0160) downregulation. In conclusion, all the let-7 family members were downregulated in LMS patients, and the greater the loss of expression of these molecules, the greater their relationship with worse prognosis of patients. Let-7e expression might influence the OS, while let-7b and le-7d might influence the DFS. The lowest expression levels of let-7d, let-7e, and let-7f were associated with the oldest patients. Our findings indicate strong evidence of let-7’s role as a potential prognostic biomarker in LMS. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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Review

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37 pages, 2113 KiB

Open AccessReview

microRNA: The Impact on Cancer Stemness and Therapeutic Resistance

by Xueqiao Jiao, Xianling Qian, Longyuan Wu, Bo Li, Yi Wang, Xinyu Kong and Lixia Xiong

Cells 2020, 9(1), 8; https://doi.org/10.3390/cells9010008 - 18 Dec 2019

Cited by 37 | Viewed by 6097

Abstract

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the [...] Read more.

Cancer ranks as the second leading cause of death worldwide, causing a large social and economic burden. However, most anti-cancer treatments face the problems of tumor recurrence and metastasis. Therefore, finding an effective cure for cancer needs to be solved urgently. Recently, the discovery of cancer stem cells (CSCs) provides a new orientation for cancer research and therapy. CSCs share main characteristics with stem cells and are able to generate an entire tumor. Besides, CSCs usually escape from current anti-cancer therapies, which is partly responsible for tumor recurrence and poor prognosis. microRNAs (miRNAs) belong to small noncoding RNA and regulate gene post-transcriptional expression. The dysregulation of miRNAs leads to plenty of diseases, including cancer. The aberrant miRNA expression in CSCs enhances stemness maintenance. In this review, we summarize the role of miRNAs on CSCs in the eight most common cancers, hoping to bridge the research of miRNAs and CSCs with clinical applications. We found that miRNAs can act as tumor promoter or suppressor. The dysregulation of miRNAs enhances cell stemness and contributes to tumor metastasis and therapeutic resistance via the formation of feedback loops and constitutive activation of carcinogenic signaling pathways. More importantly, some miRNAs may be potential targets for diagnosis, prognosis, and cancer treatments. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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20 pages, 876 KiB

Open AccessReview

Cell-Free microRNAs as Potential Oral Cancer Biomarkers: From Diagnosis to Therapy

by Óscar Rapado-González, Rafael López-López, José Luis López-Cedrún, Gabriel Triana-Martínez, Laura Muinelo-Romay and María Mercedes Suárez-Cunqueiro

Cells 2019, 8(12), 1653; https://doi.org/10.3390/cells8121653 - 17 Dec 2019

Cited by 30 | Viewed by 5848

Abstract

Oral cavity cancer is the most frequent malignancy of the head and neck. Unfortunately, despite educational interventions for prevention and early diagnosis, oral cancer patients are often diagnosed in advanced stages associated with poor prognosis and life expectancy. Therefore, there is an urgent [...] Read more.

Oral cavity cancer is the most frequent malignancy of the head and neck. Unfortunately, despite educational interventions for prevention and early diagnosis, oral cancer patients are often diagnosed in advanced stages associated with poor prognosis and life expectancy. Therefore, there is an urgent need to find noninvasive biomarkers to improve early detection of this tumor. Liquid biopsy has emerged as a valuable tool in medical oncology which provides new horizons for improving clinical decision making. Notably, cell-free microRNAs (miRNAs), a class of short non-coding RNAs, are emerging as novel noninvasive cancer biomarkers. Here, we provide an overview of the potential clinical application of cell-free miRNAs as diagnostic, prognostic, and therapeutic biomarkers in oral cancer. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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22 pages, 2362 KiB

Open AccessReview

The Butterfly Effect of RNA Alterations on Transcriptomic Equilibrium

by Ng Desi and Yvonne Tay

Cells 2019, 8(12), 1634; https://doi.org/10.3390/cells8121634 - 13 Dec 2019

Cited by 9 | Viewed by 5038

Abstract

Post-transcriptional regulation plays a key role in modulating gene expression, and the perturbation of transcriptomic equilibrium has been shown to drive the development of multiple diseases including cancer. Recent studies have revealed the existence of multiple post-transcriptional processes that coordinatively regulate the expression [...] Read more.

Post-transcriptional regulation plays a key role in modulating gene expression, and the perturbation of transcriptomic equilibrium has been shown to drive the development of multiple diseases including cancer. Recent studies have revealed the existence of multiple post-transcriptional processes that coordinatively regulate the expression and function of each RNA transcript. In this review, we summarize the latest research describing various mechanisms by which small alterations in RNA processing or function can potentially reshape the transcriptomic landscape, and the impact that this may have on cancer development. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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36 pages, 2605 KiB

Open AccessReview

MicroRNAs Involved in Carcinogenesis, Prognosis, Therapeutic Resistance, and Applications in Human Triple-Negative Breast Cancer

by Lei Ding, Huan Gu, Xianhui Xiong, Hongshun Ao, Jiaqi Cao, Wen Lin, Min Yu, Jie Lin and Qinghua Cui

Cells 2019, 8(12), 1492; https://doi.org/10.3390/cells8121492 - 22 Nov 2019

Cited by 118 | Viewed by 7357

Abstract

Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded [...] Read more.

Triple-negative breast cancer (TNBC) is the most aggressive, prevalent, and distinct subtype of breast cancer characterized by high recurrence rates and poor clinical prognosis, devoid of both predictive markers and potential therapeutic targets. MicroRNAs (miRNA/miR) are a family of small, endogenous, non-coding, single-stranded regulatory RNAs that bind to the 3′-untranslated region (3′-UTR) complementary sequences and downregulate the translation of target mRNAs as post-transcriptional regulators. Dysregulation miRNAs are involved in broad spectrum cellular processes of TNBC, exerting their function as oncogenes or tumor suppressors depending on their cellular target involved in tumor initiation, promotion, malignant conversion, and metastasis. In this review, we emphasize on masses of miRNAs that act as oncogenes or tumor suppressors involved in epithelial–mesenchymal transition (EMT), maintenance of stemness, tumor invasion and metastasis, cell proliferation, and apoptosis. We also discuss miRNAs as the targets or as the regulators of dysregulation epigenetic modulation in the carcinogenesis process of TNBC. Furthermore, we show that miRNAs used as potential classification, prognostic, chemotherapy and radiotherapy resistance markers in TNBC. Finally, we present the perspective on miRNA therapeutics with mimics or antagonists, and focus on the challenges of miRNA therapy. This study offers an insight into the role of miRNA in pathology progression of TNBC. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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38 pages, 2989 KiB

Open AccessReview

MicroRNAs and Epigenetics Strategies to Reverse Breast Cancer

by Mohammad Mijanur Rahman, Andrew C. Brane and Trygve O. Tollefsbol

Cells 2019, 8(10), 1214; https://doi.org/10.3390/cells8101214 - 8 Oct 2019

Cited by 85 | Viewed by 9272

Abstract

Breast cancer is a sporadic disease with genetic and epigenetic components. Genomic instability in breast cancer leads to mutations, copy number variations, and genetic rearrangements, while epigenetic remodeling involves alteration by DNA methylation, histone modification and microRNAs (miRNAs) of gene expression profiles. The [...] Read more.

Breast cancer is a sporadic disease with genetic and epigenetic components. Genomic instability in breast cancer leads to mutations, copy number variations, and genetic rearrangements, while epigenetic remodeling involves alteration by DNA methylation, histone modification and microRNAs (miRNAs) of gene expression profiles. The accrued scientific findings strongly suggest epigenetic dysregulation in breast cancer pathogenesis though genomic instability is central to breast cancer hallmarks. Being reversible and plastic, epigenetic processes appear more amenable toward therapeutic intervention than the more unidirectional genetic alterations. In this review, we discuss the epigenetic reprogramming associated with breast cancer such as shuffling of DNA methylation, histone acetylation, histone methylation, and miRNAs expression profiles. As part of this, we illustrate how epigenetic instability orchestrates the attainment of cancer hallmarks which stimulate the neoplastic transformation-tumorigenesis-malignancy cascades. As reversibility of epigenetic controls is a promising feature to optimize for devising novel therapeutic approaches, we also focus on the strategies for restoring the epistate that favor improved disease outcome and therapeutic intervention. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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20 pages, 1668 KiB

Open AccessReview

The Role of miRNAs in Immune Cell Development, Immune Cell Activation, and Tumor Immunity: With a Focus on Macrophages and Natural Killer Cells

by Shi Jun Xu, Hong Tao Hu, Hai Liang Li and Suhwan Chang

Cells 2019, 8(10), 1140; https://doi.org/10.3390/cells8101140 - 24 Sep 2019

Cited by 50 | Viewed by 6121

Abstract

The tumor microenvironment (TME) is the primary arena where tumor cells and the host immune system interact. Bidirectional communication between tumor cells and the associated stromal cell types within the TME influences disease initiation and progression, as well as tumor immunity. Macrophages and [...] Read more.

The tumor microenvironment (TME) is the primary arena where tumor cells and the host immune system interact. Bidirectional communication between tumor cells and the associated stromal cell types within the TME influences disease initiation and progression, as well as tumor immunity. Macrophages and natural killer (NK) cells are crucial components of the stromal compartment and display either pro- or anti-tumor properties, depending on the expression of key regulators. MicroRNAs (miRNAs) are emerging as such regulators. They affect several immune cell functions closely related to tumor evasion of the immune system. This review discusses the role of miRNAs in the differentiation, maturation, and activation of immune cells as well as tumor immunity, focusing particularly on macrophages and NK cells. Full article

(This article belongs to the Special Issue Cancer Related microRNAs)

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