MicroRNA-146a-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes

Li, Xiaodi; Jin, Yuhao; Mu, Zekun; Chen, Wei; Jiang, Siqi

doi:10.3892/ijo.2017.4023

Cited by 21 publications

(7 citation statements)

References 47 publications

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“…Cisplatin is one of the most effective chemotherapy drugs, the underlying mechanism of cisplatin resistance has been studied for decades; however, there are no effective pharmacological operations to overcome this form of complex resistance (29)(30)(31). It has been widely reported that miRNAs regulate cisplatin resistance in various cancers (31)(32)(33)(34)(35), but has rarely been reported in RCC. Recently, miR-126 targeting SERPINE1 (36) and miR-148a targeting Rab14 (37) were identified to regulate cisplatin-resistance in RCC, and it was also reported that miR-124 represses FZD5 to attenuate P-glycoprotein-mediated doxorubicinand vinblastine-resistance in RCC (38).…”

Section: Discussionmentioning

confidence: 99%

MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis

Mao¹,

Zhuang²,

Shen³

et al. 2021

Transl Androl Urol

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Background: Currently, drug-resistance is a major challenge in the treatment of renal cancer. Although microRNAs (miRNAs) have been reported to contribute to the incidence of drug resistance in renal cancer, the bio-functional roles and underlying regulatory mechanisms of novel miRNAs in cisplatin resistance remain largely unclear.Methods: In this study, miRNA microarray analysis was applied to evaluate miRNA changes induced by cisplatin on RCC (renal cell carcinoma) cell lines. Then, Caki-1 and 786-0 cells were transfected with miR (miRNA)-124 mimics to observe cisplatin resistance in RCC cell lines after up-regulation of miR-124. TargetScan was used to identify putative protein-coding gene targets of miR-124. Further, the interaction between calpain small subunit 1 (Capn4) and CCR4-NOT transcription complex subunit 3 (CNOT3) was detected by quantitative real-time PCR (qPCR) and western blotting, and confirmed by coimmunoprecipitation. The effect of Capn4 and/or CNOT3 on cell viability and half maximal inhibitory concentration (IC50) value of miR-124 overexpressed Caki-1 and 786-O cells to cisplatin was evaluated using the Cell Counting Kit-8 (CCK-8) assay. And the effect of Capn4 and/or CNOT3 on the level of necroptosis in miR-124 overexpressed Caki-1 and 786-O cells to cisplatin was evaluated by flow cytometric analysis.Then, four groups of 786-0 cells (miR-124, miR-124+ Capn4, miR-124+ CNOT3, miR-124+ Capn4+ CNOT3) were inoculated into nude mice to observe the effect of cisplatin on tumor formation.Results: miR-124 was found to be markedly elevated in renal cancer cells by cisplatin. Functionally, the overexpression of miR-124 reduced the sensitivity of renal cancer cells to cisplatin and CAPN4 was found to be a direct target of miR-124, which can negatively regulated CAPN4 expression. Moreover, ectopic expression of CAPN4 reversed the impairment of miR-124 on cisplatin-sensitivity and cisplatin-induced necroptosis. Mechanically, the present study revealed that CAPN4 could directly interact with CNOT3 and promote its degradation, and that the cisplatin-resistant phenotype was reversed by up-regulation of CNOT3.Conclusions: Therefore, miR-124 is an important inhibitor in cisplatin-induced necroptosis, and the miR-124-CAPN4-CNOT3 signaling axis plays a critical role in the emergence of cisplatin-resistance.

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Section: Discussionmentioning

confidence: 99%

MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis

Mao¹,

Zhuang²,

Shen³

et al. 2021

Transl Androl Urol

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“…Vera et al (37) demonstrated that DNA methylation of miR-7 participated in the OVC DDP resistance through MAF bZIP transcription factor G (MAFG); Yu et al (33) reported the mediation of DDP resistance in OVC by miR-21 by targeting PTEN. Additionally, Li et al (38) demonstrated that miR-146a-5p facilitated OVC DDP resistance by suppressing several antiapoptotic genes, including baculoviral IAP repeat containing (BIRC), BIRC2, BCL2L2 and X-linked inhibitor of apoptosis. Overexpression of miR-139-5p can reverse DDP resistance in OVC by targeting C-Jun (39).…”

Section: Discussionmentioning

confidence: 99%

MicroRNA‑654‑3p enhances cisplatin sensitivity by targeting QPRT and inhibiting the PI3K/AKT signaling pathway in ovarian cancer cells

et al. 2020

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Dysregulation of microRNAs serves a crucial role in the chemosensitivity to cisplatin (DDP) in ovarian cancer (OVC). The abnormal expression of microRNA (miR)-654-3p has been reported in several types of human cancer. However, the association between miR-654-3p and cisplatin resistance in human OVC remains unclear. The present study aimed to investigate the role and mechanism of miR-654-3p in DDP resistance in OVC. The results demonstrated that miR-654-3p was significantly downregulated in ovarian cancer tissues and cells, as well as DDP-resistant IGROV-1/DDP cells, compared with adjacent non-tumoral tissue and IOSE386 cells. Overexpression of miR-654-3p significantly suppressed the proliferation and migration of ovarian cancer cells and increased the sensitivity of IGROV-1/DDP cells to DDP. Luciferase reporter assay demonstrated that quinolinate phosphoribosyl transferase (QPRT) was a target of miR-654-3p; overexpression of miR-654-3p inhibited QPRT expression by binding to the 3'-untranslated region of QPRT. In addition, inhibition of miR-654-3p reversed the suppressive effects of QPRT-targeting short interfering RNA on the proliferation and chemoresistance of ovarian cancer cells. Therefore, the results of the present study revealed a previously unrecognized regulatory mechanism that miR-654-3p enhances DDP sensitivity of OVC cells by downregulating QPRT expression; in addition, the present study highlighted the therapeutic implications of miR-654-3p upregulation in OVC.

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“…There was a converse association between the levels of miR-142-5p and XIAP expressions in OC patients [ 23 ]. MiR-146a-5p also induced DDP-mediated apoptosis by XIAP, BCL2L2, and BIRC5 targeting in OC cells [ 24 ]. It has been reported that miR-509-3p , miR-519d , miR-155 , and miR-130a promoted DDP mediated apoptosis through XIAP targeting in OC cells [ 25 – 28 ].…”

Section: Main Textmentioning

confidence: 99%

“… Li [ 23 ] 2019 miR-142-5p China XIAP 19 patients SKOV3 and OVCAR3 cell lines Increased DDP sensitivity. Li [ 24 ] 2017 miR-146a-5p China XIAP, BCL2L2, and BIRC5 OVCAR3 and SKOV3 cell lines Increased DDP sensitivity. Chen [ 25 ] 2016 miR-509-3p China XIAP SKOV3 and A2780 cell lines Increased DDP sensitivity.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells

Moghbeli

2021

J Ovarian Res

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Background Ovarian cancer (OC) is one of the leading causes of cancer related deaths among women. Due to the asymptomatic tumor progression and lack of efficient screening methods, majority of OC patients are diagnosed in advanced tumor stages. A combination of surgical resection and platinum based-therapy is the common treatment option for advanced OC patients. However, tumor relapse is observed in about 70% of cases due to the treatment failure. Cisplatin is widely used as an efficient first-line treatment option for OC; however cisplatin resistance is observed in a noticeable ratio of cases. Regarding, the severe cisplatin side effects, it is required to clarify the molecular biology of cisplatin resistance to improve the clinical outcomes of OC patients. Cisplatin resistance in OC is associated with abnormal drug transportation, increased detoxification, abnormal apoptosis, and abnormal DNA repair ability. MicroRNAs (miRNAs) are critical factors involved in cell proliferation, apoptosis, and chemo resistance. MiRNAs as non-invasive and more stable factors compared with mRNAs, can be introduced as efficient markers of cisplatin response in OC patients. Main body In present review, we have summarized all of the miRNAs that have been associated with cisplatin resistance in OC. We also categorized the miRNAs based on their targets to clarify their probable molecular mechanisms during cisplatin resistance in ovarian tumor cells. Conclusions It was observed that miRNAs mainly exert their role in cisplatin response through regulation of apoptosis, signaling pathways, and transcription factors in OC cells. This review highlighted the miRNAs as important regulators of cisplatin response in ovarian tumor cells. Moreover, present review paves the way of suggesting a non-invasive panel of prediction markers for cisplatin response among OC patients.

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MicroRNA-146a-5p enhances cisplatin-induced apoptosis in ovarian cancer cells by targeting multiple anti-apoptotic genes

Cited by 21 publications

References 47 publications

MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis

MiRNA-124 regulates the sensitivity of renal cancer cells to cisplatin-induced necroptosis by targeting the CAPN4-CNOT3 axis

MicroRNA‑654‑3p enhances cisplatin sensitivity by targeting QPRT and inhibiting the PI3K/AKT signaling pathway in ovarian cancer cells

MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells

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