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环状 RNA_0000326 的沉默通过增强 microRNA-338-3p 依赖性 CDK4 的下调来抑制宫颈癌细胞的增殖、迁移和侵袭。

Silencing of circular RNA_0000326 inhibits cervical cancer cell proliferation, migration and invasion by boosting microRNA-338-3p-dependent down-regulation of CDK4.

机构信息

Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, P. R. China.

Academy of Medical Science, Zhengzhou University, Zhengzhou 450052, P. R. China.

出版信息

Aging (Albany NY). 2021 Mar 17;13(6):9119-9134. doi: 10.18632/aging.103711.

DOI:10.18632/aging.103711
PMID:33735107
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8034888/
Abstract

Cervical cancer is one of the leading causes of cancer-related death among women, which is attributed partly by limited treatment options. Recent studies have provided in-depth explanations regarding the role of circular RNA in cancers. We aimed to investigate the role of circular RNA_0000326 in cervical cancer. Bioinformatics analysis revealed a high circ_0000326 expression in cervical cancer. Cervical cancer cells and tissues were also observed to have elevated levels of circ_0000326 and the upregulation of circ_0000326 depended on the stage of cancer. Transfection with siRNA of circ_0000326 resulted in the inhibition of proliferation, migration and cell cycle of cancer cells. Interestingly, we confirmed that circ_0000326 served as a sponge for microRNA-338-3p and that the miRNA bound to Cyclin-dependent kinase 4. In the presence of microRNA-338-3p mimic or silencing of circ_0000326, Cyclin-dependent kinase 4 expression was decreased. Transfection with microRNA-338-3p mimic inhibited cell clone formation and proliferation. Moreover, experiment revealed that the injection of shRNA-circ_0000326 lentivirus suppressed tumor growth and decreased Cyclin-dependent kinase 4 expression. Taken altogether, our results showed that circ_0000326 exerted oncogenic effects on cervical cancer by upregulating Cyclin-dependent kinase 4 sponging microRNA-338-3p. This systematic investigation on circ_0000326 could provide further insight into cervical cancer.

摘要

宫颈癌是导致女性癌症相关死亡的主要原因之一,部分原因是治疗选择有限。最近的研究深入解释了环状 RNA 在癌症中的作用。我们旨在研究环状 RNA_0000326 在宫颈癌中的作用。生物信息学分析显示宫颈癌中 circ_0000326 表达较高。还观察到宫颈癌细胞和组织中 circ_0000326 水平升高,circ_0000326 的上调取决于癌症的阶段。用 siRNA 转染 circ_0000326 导致癌细胞增殖、迁移和细胞周期受到抑制。有趣的是,我们证实 circ_0000326 充当 microRNA-338-3p 的海绵,miRNA 与细胞周期蛋白依赖性激酶 4 结合。在 microRNA-338-3p 模拟物存在或 circ_0000326 沉默的情况下,细胞周期蛋白依赖性激酶 4 的表达减少。转染 microRNA-338-3p 模拟物抑制细胞克隆形成和增殖。此外,实验表明,shRNA-circ_0000326 慢病毒的转染抑制肿瘤生长并降低细胞周期蛋白依赖性激酶 4 的表达。总的来说,我们的结果表明 circ_0000326 通过上调 Cyclin-dependent kinase 4 海绵 microRNA-338-3p 对宫颈癌发挥致癌作用。对 circ_0000326 的系统研究可为宫颈癌提供进一步的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d1ed/8034888/6e81d0590ff4/aging-13-103711-g008.jpg
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