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Circ_0000263 通过调控 miR-1179/ABL2 轴促进宫颈癌的增殖并抑制其凋亡。

Circ_0000263 facilitates the proliferation and inhibits the apoptosis of cervical cancer depending on the regulation of miR-1179/ABL2 axis.

机构信息

Department of Gynecology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, China.

Department of Oncology, Renmin Hospital, Hubei University of Medicine, No.39 Chaoyang Road, Maojian District, Shiyan, 442000, Hubei, China.

出版信息

Reprod Sci. 2022 Sep;29(9):2636-2646. doi: 10.1007/s43032-022-00920-3. Epub 2022 Mar 30.

Abstract

Circular RNA (circRNA) has been reported to participate in the progression of cervical cancer (CC). Studies on the role and mechanism of circ_0000263 in CC are limited, and more studies are needed. The expression of circ_0000263, microRNA (miR)-1179 and ABL proto-oncogene 2 (ABL2) mRNA in tissues and cells was analyzed by quantitative real-time PCR. The proliferation and apoptosis of CC cells were determined using cell counting kit 8 assay, Edu assay, colony formation assay and flow cytometry. The protein expression of proliferation markers, apoptosis markers and ABL2 was detected by western blot analysis. The interaction between RNAs was estimated via dual-luciferase reporter assay. Xenograft models were applied to explore the effect of circ_0000263 knockdown on CC tumorigenesis. Circ_0000263 was highly expressed in CC tumor tissues. Silencing of circ_0000263 suppressed CC cell proliferation and increased apoptosis. Circ_0000263 served as a sponge for miR-1179, and miR-1179 inhibitor reversed the regulation of si-circ_0000263 on CC cell proliferation and apoptosis. ABL2 could be targeted by miR-1179, and circ_0000263 could sponge miR-1179 to regulate ABL2. Overexpression of ABL2 reversed the anti-proliferation and pro-apoptosis roles of miR-1179 in CC cells. In addition, circ_0000263 knockdown reduced CC tumor growth by miR-1179/ABL2 axis. In brief, the results demonstrated that circ_0000263 exerted an oncogene role in CC, which suggested that circ_0000263 might be a promising therapeutic target for CC.

摘要

环状 RNA(circRNA)已被报道参与宫颈癌(CC)的进展。关于 circ_0000263 在 CC 中的作用和机制的研究有限,需要更多的研究。通过实时定量 PCR 分析组织和细胞中 circ_0000263、微小 RNA(miR)-1179 和 ABL 原癌基因 2(ABL2)mRNA 的表达。使用细胞计数试剂盒 8 测定 CC 细胞的增殖和凋亡,Edu 测定,集落形成测定和流式细胞术。通过 Western blot 分析检测增殖标志物,凋亡标志物和 ABL2 的蛋白表达。通过双荧光素酶报告基因测定估计 RNA 之间的相互作用。应用异种移植模型探讨 circ_0000263 敲低对 CC 肿瘤发生的影响。circ_0000263 在 CC 肿瘤组织中高表达。沉默 circ_0000263 抑制 CC 细胞增殖并增加细胞凋亡。circ_0000263 是 miR-1179 的海绵体,miR-1179 抑制剂逆转了 si-circ_0000263 对 CC 细胞增殖和凋亡的调节。ABL2 可被 miR-1179 靶向,circ_0000263 可海绵 miR-1179 调节 ABL2。ABL2 的过表达逆转了 miR-1179 在 CC 细胞中的抗增殖和促凋亡作用。此外,circ_0000263 通过 miR-1179/ABL2 轴减少 CC 肿瘤的生长。总之,结果表明 circ_0000263 在 CC 中发挥致癌基因作用,这表明 circ_0000263 可能是 CC 的有前途的治疗靶标。

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