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微小RNA-217通过靶向Rho相关蛋白激酶1在宫颈癌细胞中发挥肿瘤抑制作用。

MicroRNA-217 functions as a tumor suppressor in cervical cancer cells through targeting Rho-associated protein kinase 1.

作者信息

Dong Jing, Wang Maoxiu, Ni Donghua, Zhang Lixin, Wang Wen, Cui Xiujuan, Fu Shijie, Yao Shujuan

机构信息

Department of Obstetrics and Gynecology, Jining Medical University Affiliated Tengzhou Central People's Hospital, Tengzhou, Shandong 277500, P.R. China.

Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong 250012, P.R. China.

出版信息

Oncol Lett. 2018 Nov;16(5):5535-5542. doi: 10.3892/ol.2018.9335. Epub 2018 Aug 20.

Abstract

The abnormal expression of microRNAs (miRNAs/miRs) has been widely reported in various tumor types. miR-217 was demonstrated to be aberrantly expressed in a number of tumors, including pancreatic adenocarcinoma and osteosarcoma; however, its specific expression pattern has never been investigated in cervical cancer cells. Compared with normal control, the level of Rho-associated protein kinase 1 (ROCK1) expression was markedly increased in cervical cancer tissues and cells compared with that in non-cancerous tissues and cells. The expression of miR-217 was significantly reduced in cervical cancer tissues and cell lines. Overexpression of miR-217 could suppress colony formation and the cell invasion capacity of SiHa and HeLa cells. Flow cytometry indicated that miR-217 significantly increased cell apoptosis in SiHa and HeLa cells. Dual-luciferase reporter assays demonstrated that ROCK1 was a target gene of miR-217. In addition, overexpression of ROCK1 also led to an increased invasion capacity in SiHa cells, even when miR-217 was inhibited, indicating that the anti-invasive effects of miR-217 were mediated through ROCK1. In summary, the results of the present study indicated that miR-217 functions as a tumor suppressor in cervical cancer cells, primarily by targeting ROCK1.

摘要

微小RNA(miRNA/miR)的异常表达在多种肿瘤类型中已有广泛报道。miR - 217在包括胰腺腺癌和骨肉瘤在内的多种肿瘤中被证明存在异常表达;然而,其在宫颈癌细胞中的具体表达模式尚未得到研究。与正常对照相比,宫颈癌组织和细胞中Rho相关蛋白激酶1(ROCK1)的表达水平明显高于非癌组织和细胞。miR - 217在宫颈癌组织和细胞系中的表达显著降低。miR - 217的过表达可抑制SiHa和HeLa细胞的集落形成及细胞侵袭能力。流式细胞术表明,miR - 217可显著增加SiHa和HeLa细胞的凋亡。双荧光素酶报告基因检测表明,ROCK1是miR - 217的靶基因。此外,即使miR - 217受到抑制,ROCK1的过表达也会导致SiHa细胞侵袭能力增强,这表明miR - 217的抗侵袭作用是通过ROCK1介导的。总之,本研究结果表明,miR - 217在宫颈癌细胞中作为肿瘤抑制因子发挥作用,主要是通过靶向ROCK1实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ff3/6176250/a1adecec43be/ol-16-05-5535-g00.jpg

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