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

被引:10
|
作者
Dai, Cheng [1 ]
Dai, Shi-Yuan [2 ]
Gao, Yan [1 ]
Yan, Ting [1 ]
Zhou, Qi-Yin [3 ]
Liu, Shi-jun [1 ]
Liu, Xuan [1 ]
Deng, Dan-Ni [1 ]
Wang, Dong-Hong [4 ,6 ]
Qin, Qing-Feng [1 ,6 ]
Zi, Dan [1 ,5 ]
机构
[1] Guizhou Prov Peoples Hosp, Dept Gynecol, Guiyang, Peoples R China
[2] Guizhou Prov Peoples Hosp, Dept Med Record Stat & Management, Guiyang, Peoples R China
[3] Zunyi Med Univ Guizhou Prov, Dept Gynecol, Affiliated Hosp 2, Zunyi, Peoples R China
[4] Zunyi Med Univ Guizhou Prov, Dept Gynecol, Affiliated Hosp, Zunyi, Peoples R China
[5] Guizhou Prov Peoples Hosp, Dept Gynecol, 83 East Zhongshan Rd, Guiyang 550002, Guizhou Provinc, Peoples R China
[6] Zunyi Med Univ Guizhou Prov, Dept Gynecol, Affiliated Hosp, 149 Dalian Rd, Zunyi 563000, Guizhou Provinc, Peoples R China
基金
中国国家自然科学基金;
关键词
Circ_0078607; miR-196b-5p; GAS7; ovarian cancer; platinum resistance; HEPATOCELLULAR-CARCINOMA CELLS; RESISTANCE; CISPLATIN; PROLIFERATION; PROGRESSION; CONTRIBUTES; INVASION;
D O I
10.1080/15592294.2023.2175565
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页数:13
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