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MicroRNA-630 inhibitor sensitizes chemoresistant ovarian cancer to chemotherapy by enhancing apoptosis

Authors
 Kyung Jin Eoh  ;  So Hyun Lee  ;  Hee Jung Kim  ;  Jung-Yun Lee  ;  Sunghoon Kim  ;  Sang Wun Kim  ;  Young Tae Kim  ;  Eun Ji Nam 
Citation
 Biochemical and Biophysical Research Communications, Vol.497(2) : 513-520, 2018 
Journal Title
 Biochemical and Biophysical Research Communications 
ISSN
 0006-291X 
Issue Date
2018
MeSH
Animals ; Antineoplastic Agents, Phytogenic/pharmacology* ; Apoptosis/drug effects* ; Apoptotic Protease-Activating Factor 1/genetics ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Neoplasm/drug effects* ; Female ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Mice ; MicroRNAs/antagonists & inhibitors* ; MicroRNAs/genetics ; Ovarian Neoplasms/drug therapy* ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/pathology ; Ovary/drug effects ; Ovary/metabolism ; Ovary/pathology ; Paclitaxel/pharmacology*
Keywords
Apoptosis ; MicroRNA ; Ovarian cancer ; miR-630
Abstract
MicroRNA-630 (miR-630) has been implicated in the development and progression of multiple cancers. The current study aimed to investigate the role of miR-630 in chemoresistant epithelial ovarian cancer. MiR-630 expression levels were detected in ovarian cancer cell line SKOV3 and paclitaxel-resistant SKOV3 (SKOV3-TR) via microarray and qRT-PCR. MiR-630 inhibitors and negative controls were transfected into SKOV3 and SKOV3-TR cells. Wound healing, invasion, chemosensitivity, and cell apoptosis assays were performed to determine proliferation and migration rates. Chemoresistant patient-derived xenograft (PDX) models were established and utilized to verify the effect of miR-630 on chemoresistant ovarian cancer. Inhibition of miR-630 decreased cell proliferation and enhanced the sensitivity of SKOV3-TR and SKOV3 cells to paclitaxel. In the chemosensitivity assay, we observed that the miR-630 inhibitor exhibited a synergistic effect with paclitaxel on SKOV3-TR cells. Inhibition was correlated with enhanced expression of apoptosis-related proteins. APAF-1 was predicted to be a potential target of miR-630. An in vivo PDX study showed that the miR-630 inhibitor sensitized chemoresistant ovarian cancer to paclitaxel. Thus, miR-630 inhibitor sensitizes chemoresistant epithelial ovarian cancer to chemotherapy by enhancing apoptosis. Our findings suggest that miR-630 might be a potential therapeutic target for chemotherapy-resistant ovarian cancer.
Full Text
https://www.sciencedirect.com/science/article/pii/S0006291X18302857
DOI
10.1016/j.bbrc.2018.02.062
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
Yonsei Authors
김상운(Kim, Sang Wun) ORCID logo https://orcid.org/0000-0002-8342-8701
김성훈(Kim, Sung Hoon) ORCID logo https://orcid.org/0000-0002-1645-7473
김영태(Kim, Young Tae) ORCID logo https://orcid.org/0000-0002-7347-1052
남은지(Nam, Eun Ji)
어경진(Eoh, Kyung Jin) ORCID logo https://orcid.org/0000-0002-1684-2267
이정윤(Lee, Jung-Yun) ORCID logo https://orcid.org/0000-0001-7948-1350
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/163126
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