MicroRNA-509–3p Increases the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin-Induced Apoptosis

Chen, Wei; Li, Xiaodi; Xiong, Weiliang; Zhang, Mengdie; Huang, Yan; Zhou, Li; Jiang, Siqi

doi:10.2217/pgs.15.166

Cited by 24 publications

(24 citation statements)

References 27 publications

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“…MiR-509-3p has been reported to act as a tumour suppressor by inhibiting gastric cancer cell proliferation and migration, and its overexpression was shown to induce apoptosis and inhibit breast and lung cancer cell invasion 33 , 34 . MiR-509-3p was found to suppress metastasis in breast cancer cells and increase the sensitivity of epithelial ovarian cancer cells to cisplatin-induced apoptosis 35 . It was also recently reported that miR-509-3p directly targets YAP and miR-509-3p mimic decreased YAP expression, thereby suppressing migration of ovarian cancer cells 36 .…”

Section: Discussionmentioning

confidence: 99%

CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway

Jung

Park

Kim

et al. 2017

Sci Rep

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Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action. CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies.

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Section: Discussionmentioning

confidence: 99%

CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway

Jung

Park

Kim

et al. 2017

Sci Rep

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“…MiR-509-3p has been reported to sensitize ovarian cancer cells to cisplatin treatment by targeting multiple anti-apoptosis genes including BCL2 [129,130] . Niu et al [131] compared the expression profiles of miRNAs between three pairs of platinum-resistant and platinum-sensitive ovarian tissues and found that miR-509-3p was significantly down-regulated in cisplatin-resistant ovarian cancer tissues.…”

mentioning

confidence: 99%

Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

Schwarzenbach¹,

Gahan²

2019

CDR

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Initially, most ovarian tumors respond to the treatment with platinum components, but frequently recurrence occurs within the following two years in advanced ovarian cancer patients. In this regard, previous studies have shown changes in the epigenetic patterns in ovarian cancer that are linked with resistance to cis-and carboplatin therapy. Thus, epigenetic changes mediated by a treatment with cis-or carboplatin could identify such patients who do or do not respond to this therapy. Therefore, an understanding of the impact of platinum on epigenetics in ovarian cancer is important in overcoming platinum resistance. In this review, we delineate epigenetic abnormalities in cis-and carboplatin-resistant ovarian tumors, such as changes in DNA methylation, histone modifications and deregulation of microRNAs, and discuss the potential of epigenetic therapies in combination with platinum.

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“…After seeding onto a 48-well plate, OVCAR3 cells were transfected with miR-146a-5p mimic, mimic control, miR-146a-5p inhibitor or inhibitor control. Cisplatin treatment and DAPI staining were performed as previously described (43). Our results show that more apoptotic nuclei were observed in OVCAR3 cells transfected with miR-146a-5p mimic compared to mimic control ( Fig.…”

Section: Transfection Of Rna Oligonucleotidesmentioning

confidence: 54%

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

Jin

et al. 2017

International Journal of Oncology

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MicroRNAs play a crucial role in gene expression regulation in various types of cancers. Previous studies show the expression level of miR‑146a‑5p is downregulated in epithelial ovarian cancer. Further investigations suggest this downregulation is responsible for apoptosis resistance in ovarian cancer cells. However, the mechanism of how miR‑146a‑5p promotes apoptosis remains unclear. In this study, the role of miR‑146a‑5p in cisplatin‑induced apoptosis of ovarian cancer cells was assessed by DAPI staining, MTT assays, and monitoring expression of XIAP, BCL2L2, BIRC2 and BIRC5 through a dual‑luciferase assay. Our results show that miR‑146a‑5p can regulate three important anti‑apoptotic genes including XIAP, BCL2L2 and BIRC5 via their 3'UTRs. Not only can overexpression of miR‑146a‑5p downregulate the expression of XIAP in SKOV3 cells, but it also lowers the IC50 values of cisplatin in OVCAR3 and SKOV3 cells and enhances the susceptibility of OVCAR3, SKOV3 and primary ovarian cancer cells to cisplatin‑induced apoptosis. The effect of XIAP rescuing cisplatin‑induced apoptosis accelerated by miR‑146a‑5p further supports our conclusion. Our results suggest that the regulation of three anti‑apoptotic genes by miR‑146‑5p enhances the therapeutic effects of cisplatin.

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MicroRNA-509–3p Increases the Sensitivity of Epithelial Ovarian Cancer Cells to Cisplatin-Induced Apoptosis

Abstract: Our data suggest that restoring certain dysregulated miRNAs to their normal levels could increase the therapeutic effects of anticancer drugs.

Cited by 24 publications

References 27 publications

CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway

CG200745, an HDAC inhibitor, induces anti-tumour effects in cholangiocarcinoma cell lines via miRNAs targeting the Hippo pathway

Resistance to cis- and carboplatin initiated by epigenetic changes in ovarian cancer patients

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

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