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长链非编码RNA HNF1A-AS1通过上调Bcl-2促进膀胱癌细胞增殖并抑制其凋亡。

Long non-coding RNA HNF1A-AS1 promotes proliferation and suppresses apoptosis of bladder cancer cells through upregulating Bcl-2.

作者信息

Zhan Yonghao, Li Yifan, Guan Bao, Wang Zicheng, Peng Ding, Chen Zhicong, He Anbang, He Shiming, Gong Yanqing, Li Xuesong, Zhou Liqun

机构信息

Department of Urology, Peking University First Hospital, The Institute of Urology, Peking University, National Urological Cancer Centre, Beijing, 100034, China.

Department of Urology, State Engineering Laboratory of Medical Key Technologies Application of Synthetic Biology, Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China.

出版信息

Oncotarget. 2017 Sep 8;8(44):76656-76665. doi: 10.18632/oncotarget.20795. eCollection 2017 Sep 29.

Abstract

Emerging evidences have indicated that long non-coding RNAs (lncRNAs) are pivotal regulators of tumor development and progression. HNF1A-AS1 (HNF1A antisense RNA 1, C12 or f27) is a novel long non-coding RNA that acts as a potential biomarker and is involved in development and progression of several cancers. Nevertheless, we know nothing about the clinical significance and molecular mechanism of HNF1A-AS1 in bladder cancer. In this study, we found that HNF1A-AS1 is significantly up-regulated in bladder cancer. Further experiments had demonstrated that silencing HNF1A-AS1 in bladder cancer cells could inhibit the proliferation and induce apoptosis. Mechanistically, we found down-regulated of HNF1A-AS1 increased the expression of miR-30b-5p and subsequently inhibited the expression of Bcl-2, in a ceRNA-dependent way. Moreover, knockdown of miR-30b-5p reversed cell proliferation inhibition and cell apoptosis induced by silencing HNF1A-AS1. In conclusions, we demonstrated that HNF1A-AS1 plays an important regulatory role in bladder cancer and shed new light on lncRNA-directed diagnostic and therapeutics in bladder cancer.

摘要

新出现的证据表明,长链非编码RNA(lncRNAs)是肿瘤发生和发展的关键调节因子。HNF1A-AS1(HNF1A反义RNA1,C12或f27)是一种新型长链非编码RNA,作为一种潜在的生物标志物,参与多种癌症的发生和发展。然而,我们对HNF1A-AS1在膀胱癌中的临床意义和分子机制一无所知。在本研究中,我们发现HNF1A-AS1在膀胱癌中显著上调。进一步的实验表明,沉默膀胱癌细胞中的HNF1A-AS1可以抑制细胞增殖并诱导细胞凋亡。机制上,我们发现下调HNF1A-AS1以ceRNA依赖的方式增加了miR-30b-5p的表达,随后抑制了Bcl-2的表达。此外,敲低miR-30b-5p可逆转沉默HNF1A-AS1诱导的细胞增殖抑制和细胞凋亡。总之,我们证明了HNF1A-AS1在膀胱癌中起重要调节作用,并为膀胱癌中lncRNA导向的诊断和治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e3bd/5652733/7e4c4441b667/oncotarget-08-76656-g001.jpg

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