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Hsa_circRNA_100146作为miR-149-5p的海绵,通过调节……促进膀胱癌进展。

Hsa_circRNA_100146 Acts as a Sponge of miR-149-5p in Promoting Bladder Cancer Progression via Regulating .

作者信息

Wang Hengbing, Niu Xiaobing, Mao Fei, Liu Xuzhong, Zhong Bing, Jiang Hesong, Fu Guangbo

机构信息

Department of Urology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu Province, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Oct 29;13:11007-11017. doi: 10.2147/OTT.S273622. eCollection 2020.

Abstract

BACKGROUND

Mounting evidence has demonstrated that circular RNAs (circRNAs) play indispensable roles in the progression of bladder cancer. Public database mining showed that hsa_circRNA_100146 (circRNA_100146) was highly expressed in bladder cancer. This study aimed to characterize the biological role of circRNA_100146 and clarify the underlying mechanism in bladder cancer.

METHODS

We evaluated the relationship between circRNA_100146 expression and clinicopathological features. Furthermore, gain- and loss-of-function studies were conducted in bladder cancer cells via transfection with gene-carrying plasmids (over-expression) or specific short hairpin RNAs (knockdown). Moreover, computational algorithms and dual-luciferase reporter assays were performed to explore the possible mechanisms of action. Additionally, in vivo xenograft experiments were performed to further analyze the effect of circRNA_100146 on tumor growth.

RESULTS

Our data showed that circRNA_100146 expression was increased in bladder cancer tissues and cell lines, and that high expression of circRNA_100146 was correlated with poor patient prognosis. Upregulation of circRNA_100146 promoted cell proliferation, migration, and invasion, and inhibited cell apoptosis, whereas knockdown of circRNA_100146 displayed opposite effects on bladder cancer cells. Notably, circRNA_100146 could combine with miR-149-5p and promote ring finger protein 2 () expression, thereby facilitating the progression of bladder cancer. Furthermore, overexpression of reversed the effects of circRNA_100146 knockdown on the biological behaviors of bladder cancer cells. The in vivo experiments revealed that downregulation of circRNA_100146 dramatically delayed tumor growth.

CONCLUSION

Our findings indicate that circRNA_100146 functions as a sponge of miR-149-5p in promoting bladder cancer progression by regulating expression and that circRNA_100146 may serve as a novel biomarker in human bladder cancer.

摘要

背景

越来越多的证据表明,环状RNA(circRNA)在膀胱癌进展中发挥着不可或缺的作用。公共数据库挖掘显示,hsa_circRNA_100146(circRNA_100146)在膀胱癌中高表达。本研究旨在表征circRNA_100146的生物学作用,并阐明其在膀胱癌中的潜在机制。

方法

我们评估了circRNA_100146表达与临床病理特征之间的关系。此外,通过用携带基因的质粒转染(过表达)或特异性短发夹RNA(敲低)在膀胱癌细胞中进行功能获得和功能丧失研究。此外,进行了计算算法和双荧光素酶报告基因测定以探索可能的作用机制。另外,进行了体内异种移植实验以进一步分析circRNA_100146对肿瘤生长的影响。

结果

我们的数据显示,circRNA_100146在膀胱癌组织和细胞系中表达增加,并且circRNA_100146的高表达与患者预后不良相关。circRNA_100146的上调促进细胞增殖、迁移和侵袭,并抑制细胞凋亡,而circRNA_100146的敲低对膀胱癌细胞显示出相反的作用。值得注意的是,circRNA_100146可以与miR-149-5p结合并促进环状指蛋白2()表达,从而促进膀胱癌的进展。此外,的过表达逆转了circRNA_100146敲低对膀胱癌细胞生物学行为的影响。体内实验表明,circRNA_100146的下调显著延迟了肿瘤生长。

结论

我们的研究结果表明,circRNA_100146作为miR-149-5p的海绵,通过调节表达促进膀胱癌进展,并且circRNA_100146可能作为人类膀胱癌的一种新型生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76af/7605652/ae4a6d4288e6/OTT-13-11007-g0001.jpg

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