Current updates on microRNAs as regulators of chemoresistance

Caliskan, Metin; Güler, Hale; Çetintaş, Vildan Bozok

doi:10.1016/j.biopha.2017.08.084

Cited by 20 publications

(11 citation statements)

References 189 publications

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“…Although numerous mechanisms contribute to chemoresistance, including increased drug efflux, inactivation of detoxification enzymes, alterations in drug metabolism, mutations of drug targets, dysfunction of pro-apoptotic proteins and enhancement of DNA repair activity, the mechanisms involved in cancer chemoresistance remain poorly understood (24)(25)(26)(27)(28). Evidence suggests that miRNAs are involved in chemoresistance in various types of cancer, including GC (6,14). However, relatively few studies investigating MDR in GC have been performed.…”

Section: Discussionmentioning

confidence: 99%

“…Micro (mi)RNAs are short (20-24 nt), stable, non-coding RNA molecules that negatively regulate 60% of coding genes by targeting the 3' untranslated regions (3'UTRs) of specific mRNAs to prevent translation and/or promote degradation (5). Accumulating evidence indicates that miRNAs serve important roles in chemoresistance in various types of cancer, including GC (6)(7)(8)(9)(10)(11)(12)(13)(14). However, the exact mechanisms underlying the regulation of chemoresistance in GC by miRNAs remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Huang¹,

Tang

Zhang

et al. 2018

Int J Oncol

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Chemotherapy is an important treatment option for gastric cancer (GC); however, chemotherapy usually fails due to drug resistance, particularly multidrug resistance (MDR). In our previous studies, microRNA (miR)-874 was demonstrated to serve an important role in tumour growth, apoptosis and angiogenesis. In the present study, the precise roles and underlying mechanisms of miR-874 in MDR were investigated in GC. The overexpression of miR-874 reversed cancer cell drug resistance in vitro. According to reporter gene and western blot assays, Autophagy-related 16-like 1 (ATG16 L1) was identified as a direct target of miR-874. ATG16L1 was also demonstrated to be positively associated with autophagy. Reducing the expression of ATG16L1 and inhibiting the occurrence of autophagy sensitized GC cells to chemotherapy. Thus, the miR-874/ATG16L1/autophagy regulatory loop was demonstrated to serve an important role in MDR in GC. Furthermore, miR-874 may be used as a prognostic factor in GC. Overall, miR-874 could inhibit autophagy and sensitize GC cells to chemotherapy via the target gene ATG16L1, highlighting the potential clinical application of miR-874 in chemotherapeutic resistance.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Huang¹,

Tang

Zhang

et al. 2018

Int J Oncol

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“…It was found that targeted regulating of the expression of Wee1 and ChK1 by miR-15a could restore the sensitivity of cisplatin-resistant cells. bozok et al (22) and Çalışkan et al (23) confirmed that miR-15a enhanced the anti-tumor effect of platinum chemotherapeutic drugs in drug-resistant NSCLC. In other studies, miRNA-15 family suppressed cell metastasis by regulating EMT process in malignant cancer cells (24)(25)(26).…”

Section: Discussionmentioning

confidence: 93%

Inhibition mechanism of lung cancer cell metastasis through targeted regulation of Smad3 by miR‑15a

Guo

et al. 2019

Oncol Lett

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Effect of targeted regulation of mothers against decapentaplegic homolog 3 (Smad3) by microRNA-15a (miR-15a) on the proliferation, invasion and metastasis of non-small cell lung cancer (NSCLC) cells and its related mechanisms were investigated. Fifty pairs of NSCLC and para-cancerous tissues were collected to identify the expression level of miR-15a in NSCLC, para-cancerous tissue, and cell lines A549, H1299, H1975 and BEAS-2B by real-time fluorescence quantitative PCR (RT-PCR); A549 cells were transfected with miR-15a mimic; the MTT assay was performed to detect the role of miR-15a transfection in proliferation of A549 cells, the wound healing assay was carried out to identify the role of miR-15a in migration of A549 cells; Transwell invasion assay was conducted to analyze the role of miR-15a in invasion of A549 cells; western blotting was carried out to find the effect of miR-15a on Smad3 expression, and Spearman's rank correlation was used to analyze the correlation between miR-15a and Smad3 expression. NSCLC tissues and cells showed significantly lower miR-15a expression, compared with para-cancerous tissues and normal cell lines (P=0.023). miR-15a was significantly more expressed in A549 cells transfected with miR-15a mimic (P=0.043). Overexpression of miR-15a can significantly inhibit A549 cell proliferation (P=0.038), migration (P=0.033) and invasion (P=0.025), and significantly reduced the expression level of Smad3 (P=0.031) in A549 cells. Spearman's rank correlation showed negative correlation of miR-15a expression with Smad3, which may indicate negative regulation (r=-0.34, P<0.0001). Inhibition of proliferation, migration and invasion of NSCLC cells can be achieved with targeted regulation of Smad3 by miR-15a.

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“…Chemoresistance in cancer is the main cause of treatment failure (3). Recent data indicated that aberrant miRNA expression was closely linked to chemoresistance by targeting genes related to chemosensitivity or chemoresistance (25). However, specific chemoresistance-related miRNAs are largely unknown.…”

Section: Discussionmentioning

confidence: 99%

miR‑584 inhibits cell proliferation, migration and invasion in�vitro and enhances the sensitivity to cisplatin in human cervical cancer by negatively targeting GLI1

2020

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Cervical cancer is the most lethal malignancy amongst women worldwide. MicroRNAs (miRNAs/miRs) play a critical role in the progression of cervical cancer. Compelling evidence indicates that miR-584 acts as a tumor suppressor in some types of cancers. However, the function of miR-584 in cervical cancer has not been illustrated. In the present study, the effects and mechanism of miR-584 in the process of proliferation, migration and invasion, and drug sensitivity to cisplatin in cervical cancer were determined. miR-584 expression decreased markedly in cervical cancer tissues and cell lines compared with healthy control samples. Dual-luciferase reporter assays confirmed that glioma-associated oncogene 1 (GLI1) is a novel molecular target of miR-584. The overexpression of miR-584 inhibited the expression of GLI1, reduced cell proliferation, migration and invasion, and induced apoptosis in HeLa cells. However, the silencing of miR-584 in CaSki cells produced the opposite effects. In addition, the overexpression of GLI1 in HeLa-cells overexpressing miR-584 markedly reversed the miR-584-induced inhibitory effect. Flow cytometry results showed that miR-584 enhanced cisplatin sensitivity by promoting chemotherapy-induced apoptosis. Therefore, miR-584 acted as a tumor suppressor miRNA and might be a novel target gene for future cervical cancer treatments.

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Current updates on microRNAs as regulators of chemoresistance

Cited by 20 publications

References 189 publications

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

miR-874 regulates multiple-drug resistance in gastric cancer by targeting ATG16L1

Inhibition mechanism of lung cancer cell metastasis through targeted regulation of Smad3 by miR‑15a

miR‑584 inhibits cell proliferation, migration and invasion in�vitro and enhances the sensitivity to cisplatin in human cervical cancer by negatively targeting GLI1

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