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Circ_0078607 increases platinum drug sensitivity via miR-196b-5p/GAS7 axis in ovarian cancer

Authors :
Cheng Dai
Shi-Yuan Dai
Yan Gao
Ting Yan
Qi-Yin Zhou
Shi-jun Liu
Xuan Liu
Dan-Ni Deng
Dong-Hong Wang
Qing-Feng Qin
Dan Zi
Source :
Epigenetics, Vol 18, Iss 1 (2023)
Publication Year :
2023
Publisher :
Taylor & Francis Group, 2023.

Abstract

Platinum-based chemotherapy is one of the predominant strategies for treating ovarian cancer (OC), however, platinum resistance greatly influences the therapeutic effect. Circular RNAs (circRNAs) have been found to participate in the pathogenesis of platinum resistance. Our aim was to explore the involvement of circ_0078607 in OC cell cisplatin (DDP) resistance and its potential mechanisms. Circ_0078607, miR-196b-5p, and growth arrest-specific 7 (GAS7) levels were assessed by qPCR. Circ_0078607 stability was assessed by ribonuclease R digestion and actinomycin D treatment. Cell viability of various conic of DDP treatment was measured by CCK-8. The cell proliferation was determined by CCK-8 and colony formation assay. Western blotting was performed for determining GAS7, ABCB1, CyclinD1 and Bcl-2 protein levels. The direct binding between miR-196b-5p and circ_0078607 or GAS7 was validated by dual-luciferase reporter and RIP assay. DDP resistance in vivo was evaluated in nude mice. Immunohistochemistry staining for detecting Ki67 expression in xenograft tumours. Circ_0078607 and GAS7 was down-regulated, but miR-196b-5p was up-regulated in OC samples and DDP-resistant cells. Overexpression of circ_0078607 inhibited DDP resistance, cell growth and induced apoptosis in DDP-resistant OC cells. Mechanistically, circ_0078607 sequestered miR-196b-5p to up-regulate GAS7. MiR-196b-5p mimics reversed circ_0078607 or GAS7 overexpression-mediated enhanced sensitivity. Finally, circ_0078607 improved the sensitivity of DDP in vivo. Circ_0078607 attenuates DDP resistance via miR-196b-5p/GAS7 axis, which highlights the therapeutic potential of circ_0078607 to counter DDP resistance in OC.

Details

Language :
English
ISSN :
15592294 and 15592308
Volume :
18
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Epigenetics
Publication Type :
Academic Journal
Accession number :
edsdoj.649686b6ce78407b90d4274de91435e9
Document Type :
article
Full Text :
https://doi.org/10.1080/15592294.2023.2175565