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LINC01638长链非编码RNA通过上调ROCK2介导膀胱癌术后远处复发。

LINC01638 lncRNA mediates the postoperative distant recurrence of bladder cancer by upregulating ROCK2.

作者信息

Yuan Shouxian, Luan Xiuhua, Han Guiqiang, Guo Kecun, Wang Shenghui, Zhang Xiangkai

机构信息

Department of Urology Surgery, The Second People's Hospital of Liaocheng, Linqing, Shandong 252600, P.R. China.

Department of Urology Surgery, The People's Hospital of Liqing, Linqing, Shandong 252600, P.R. China.

出版信息

Oncol Lett. 2019 Nov;18(5):5392-5398. doi: 10.3892/ol.2019.10924. Epub 2019 Sep 26.

Abstract

It is well established that long intergenic non-protein coding RNA 1638 (LINC01638) promotes the development and progression of breast cancer, whereas its roles in other human diseases are currently unknown. In the present study, expression of LINC01638 and ROCK2 was analyzed using quantitative PCR, ELISA and western blot. Receiver operating characteristic curve was used for diagnostic analysis. Cell transfections were performed to analyze interactions between LINC01638 and ROCK2, while Transwell assays were performed to analyze invasion and migration of the bladder cancer HT-1197 and HT-1376 cell lines. It was observed that LINC01638 and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) were significantly upregulated in the plasma of patients with early stage (stage I and II) bladder cancer compared with in healthy controls. Upregulation of LINC01638 and ROCK2 distinguished patients with early stage bladder cancer from healthy controls. Plasma levels of LINC01638 and ROCK2 were positively correlated in patients with bladder cancer, but not in healthy controls. A follow-up study after surgical resection revealed that LINC01638 and ROCK2 were further upregulated in patients with distant recurrence, or distant and local recurrence, but not in patients with local recurrence and no recurrence. Overexpression of LINC01638 led to ROCK2 upregulation in bladder cancer cells, whereas ROCK2 overexpression did not significantly affect LINC01638 expression. Overexpression of LINC01638 and ROCK2 mediated the promoted migration and invasion of bladder cancer cells, and ROCK2 small interfering RNA silencing attenuated the enhancing effects of LINC01638 on cancer cell migration and invasion. Therefore, LINC01638 may mediate the postoperative distant recurrence of bladder cancer by upregulating ROCK2.

摘要

长链基因间非编码RNA 1638(LINC01638)促进乳腺癌的发展和进展,这一点已得到充分证实,而其在其他人类疾病中的作用目前尚不清楚。在本研究中,采用定量PCR、酶联免疫吸附测定(ELISA)和蛋白质印迹法分析了LINC01638和Rho相关卷曲螺旋蛋白激酶2(ROCK2)的表达。采用受试者工作特征曲线进行诊断分析。进行细胞转染以分析LINC01638和ROCK2之间的相互作用,同时进行Transwell实验以分析膀胱癌HT-1197和HT-1376细胞系的侵袭和迁移。结果发现,与健康对照相比,早期(I期和II期)膀胱癌患者血浆中LINC01638和ROCK2显著上调。LINC01638和ROCK2的上调可将早期膀胱癌患者与健康对照区分开来。膀胱癌患者血浆中LINC01638和ROCK2水平呈正相关,而健康对照者则无此相关性。手术切除后的随访研究显示,远处复发或远处及局部复发患者中LINC01638和ROCK2进一步上调,而局部复发且无复发患者中则未上调。LINC01638的过表达导致膀胱癌细胞中ROCK2上调,而ROCK2的过表达对LINC01638的表达无显著影响。LINC01638和ROCK2的过表达介导了膀胱癌细胞迁移和侵袭的促进作用,ROCK2小干扰RNA沉默减弱了LINC01638对癌细胞迁移和侵袭的增强作用。因此,LINC01638可能通过上调ROCK2介导膀胱癌术后远处复发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6744/6788173/541a631ca57b/ol-18-05-5392-g00.jpg

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