目的:探讨circ_0000135/miR-140-3p/PDZ结构域含1(PDZK1)在宫颈癌发生发展中的作用。
方法:收集临床数据以验证circ_0000135/miR-140-3p/PDZK1在宫颈癌中的表达。实时定量PCR检测circ_0000135和miR-140-3p的mRNA表达。体外分析circ_0000135和miR-140-3p/miR-140-3p与PDZK1的相关性。通过Westernblot检测细胞中的蛋白表达;而细胞增殖,CCK8检测的侵袭和周期分布,Transwell室测定和流式细胞术,分别。进行抢救和动物实验以验证circ_0000135/miR-140-3p/PDZK1对宫颈癌的作用。
结果:circ_0000135和PDZK1表达增加,而miR-140-3p在宫颈癌组织和细胞中的表达均降低(均P<0.05)。sh-circ_0000135组细胞活力下降,在G0/G1期被捕细胞,CyclinD1表达减少,抑制细胞迁移和侵袭;sh-circ_0000135组肿瘤体积减小,体重,Ki67表达降低(均P<0.05)。circ_0000135具有miR-140-3p的保守靶标。在circ_0000135和miR-140-3p之间存在直接相互作用。miR-140-3p可能与PDZK1有直接相互作用。sh-circ_0000135和/或miR-140-3p处理显示PDZK1表达明显降低,细胞活性降低,在G0/G1期被捕细胞,下调细胞迁移和侵袭;sh-circ_0000135和/或miR-140-3p模拟物治疗显示肿瘤体积明显减小,肿瘤重量,Ki67表达(均P<0.05)。
结论:circ_0000135可能通过使用miR-140-3p抑制PDZK1的表达在宫颈癌的进展中起抗肿瘤作用,提供了一个有前景的治疗靶点。
OBJECTIVE: To explore the effect of circ_0000135/miR-140-3p/PDZ domain containing 1 (
PDZK1) on the occurrence and development of cervical cancer.
METHODS: Clinical data were collected to verify circ_0000135/miR-140-3p/
PDZK1 expression in cervical cancer. mRNA expressions of circ_0000135 and miR-140-3p were detected by real-time quantitative PCR. Correlation between circ_0000135 and miR-140-3p/miR-140-3p and
PDZK1 was analyzed in vitro. Protein expression detection in cells was conducted by Western blot; while cell proliferation, invasion and cycle distribution by CCK8 assay, Transwell chamber assay and flow cytometry, respectively. Rescue and animal experiment were performed to verify the effect of circ_0000135/miR-140-3p/
PDZK1 on cervical cancer.
RESULTS: circ_0000135 and
PDZK1 expressions were increased, while those of miR-140-3p were decreased in cervical cancer tissues and cells (both P < 0.05). sh-circ_0000135 group had decreased cell viability, arrested cells in G0/G1 phase, decreased CyclinD1 expression, inhibited cell migration and invasion; sh-circ_0000135 group showed reduced tumor volume, weight, and lower Ki67 expression (all P < 0.05). circ_0000135 had conserved target of miR-140-3p. There was a direct interaction between circ_0000135 and miR-140-3p. miR-140-3p might have direct interaction with PDZK1. sh-circ_0000135 and/or miR-140-3p treatment showed obviously decreased PDZK1 expression, decreased cell activity, arrested cells in G0/G1 phase, downregulated cell migration and invasion; sh-circ_0000135 and/or miR-140-3p mimic treatment showed obviously decreased tumor volume, tumor weight, and Ki67 expression (all P < 0.05).
CONCLUSIONS: circ_0000135 may play an anti-tumor role on the progression of cervical cancer by sponging miR-140-3p to suppress the expression of PDZK1, providing a promising therapeutic target.