CircITGB6调节miR-542-3p/PCNA轴对卵巢癌细胞顺铂耐药性的影响及其机制

doi:10.3969/j.issn.1006-6233.2023.08.03

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Abstract Objective: To investigate the influences of circular RNA (Circ) ITGB6 on cisplatin (DDP) resistance of ovarian cancer (OC) cells by regulating miR-542-3p/proliferating cell nuclear antigen (PCNA) axis and its mechanism. Methods: The expression levels of CircITGB6, miR-542-3p, PCNA mRNA in OC tissues, normal ovarian tissues, SKOV3, SKOV3/DDP and normal ovarian epithelial cell line (IOSE-80) were detected by qRT-PCR; SKOV3/DDP was set as control group (no treatment), interference (si CircITGB6) group (transfected with si CircITGB6), negative control (si NC) group (transfected with si NC), si CircITGB6+inhibitor negative control (inhibitor NC) group (co-transfected with si CircITGB6 and inhibitor NC), and si CircITGB6+miR-542-3p inhibitor group (co-transfected with si CircITGB6 and miR-542-3p inhibitor). Apoptosis, proliferation, drug resistance, and the expression levels of CircITGB6, miR-542-3p, PCNA mRNA in SKOV3/DDP cells of each group were detected by flow cytometry, CCK-8 and qRT PCR respectively; double luciferase was used to verify the targeting relationship between miR-542-3p and CircITGB6, PCNA; the PCNA, Bcl-2 associated X protein (Bax) and cell proliferation related nuclear antigen (Ki-67) were detected by Western blot. Results: The expression of CircITGB6 (1.66±0.17 vs 0.95±0.10) and PCNA mRNA (1.59±0.16 vs 0.98±0.10) in OC tissues was higher than that in normal ovarian tissues, and the expression of miR-542-3p (0.64±0.07 vs 1.06±0.11) was lower (all P<0.05); the expression of CircITGB6 and PCNA mRNA in IOSE-80, SKOV3 and SKOV3/DDP increased in turn, the expression of miR-542-3p decreased in turn (P<0.05); compared with the control group and the si NC group, the cell proliferation rate and IC50, CircITGB6 (1.21±0.13 vs 1.88±0.19, 1.84±0.19), Ki-67, PCNA in the si CircITGB6 group were obviously reduced, the apoptosis rate and expression of Bax and miR-542-3p (0.86±0.09 vs 0.51±0.06, 0.55±0.06) were obviously increased (all P<0.05); compared with the si CircITGB6+inhibitor NC group, the cell proliferation rate and IC50, Ki-67, PCNA in the CircITGB6+miR-542-3p inhibitor group were obviously increased, the apoptosis rate and the expression of Bax and miR-542-3p were obviously decreased (all P<0.05). Conclusion: Interfering with CircITGB6 expression can reduce the resistance of SKOV3 to DDP by regulating miR-542-3p/PCNA axis.

Key words： Ovarian cancer Cisplatin resistance CircITGB6 MiR-542-3p PCNA

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.08.03 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I8/1245

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