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LncARSR 通过增加 SOX4 表达来海绵吸附 miR-129-5p,从而促进膀胱癌细胞的增殖和转移。

LncARSR sponges miR-129-5p to promote proliferation and metastasis of bladder cancer cells through increasing SOX4 expression.

机构信息

Department of Urology, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde), Foshan City 528308, Guangdong Province, China.

Institute of Urology, Peking University Shenzhen Hospital, Shenzhen 518000, China.

出版信息

Int J Biol Sci. 2020 Jan 1;16(1):1-11. doi: 10.7150/ijbs.39461. eCollection 2020.

Abstract

Emerging evidences have indicated that long non-coding RNAs (lncRNAs) are potential biomarkers, playing important roles in the development of cancer. LncRNA Activated in RCC with Sunitinib Resistance (lncARSR) is a novel lncRNA that functions as a potential biomarker and is involved in the progression of cancers. However, the clinical significance and molecular mechanism of lncARSR in bladder cancer (Bca) remains unknow. In this study, we discovered that lncARSR was significantly up-regulated in bladder cancer. In addition, increased expression of lncARSR was positively correlated with higher histological grade and larger tumor size. Further experiments demonstrated that suppression of lncARSR attenuated the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process of Bca cells. Mechanistically, lncARSR was mainly located in the cytoplasm and acted as a miRNA sponge to positively modulate the expression of Sex-determining region Y-related high-mobility-group box transcription factor 4 (SOX4) via sponging miR-129-5p and subsequently promoted the proliferation and metastasis of Bca cells, thus playing an oncogenic role in Bca pathogenesis. In conclusion, our study indicated that lncARSR plays a critical regulatory role in Bca cells and lncARSR may serve as a potential diagnostic biomarker and therapeutic target for bladder cancer.

摘要

越来越多的证据表明,长非编码 RNA(lncRNA)是潜在的生物标志物,在癌症的发展中发挥着重要作用。lncRNAActivated in RCC with Sunitinib Resistance(lncARSR)是一种新型的 lncRNA,作为一种潜在的生物标志物,参与癌症的进展。然而,lncARSR 在膀胱癌(Bca)中的临床意义和分子机制尚不清楚。在本研究中,我们发现 lncARSR 在膀胱癌中显著上调。此外,lncARSR 的高表达与较高的组织学分级和较大的肿瘤大小呈正相关。进一步的实验表明,抑制 lncARSR 可减弱 Bca 细胞的增殖、迁移、侵袭和上皮间质转化(EMT)过程。机制上,lncARSR 主要位于细胞质中,并作为 miRNA 海绵通过海绵 miR-129-5p 正向调节性别决定区 Y 相关高迁移率族盒转录因子 4(SOX4)的表达,从而促进 Bca 细胞的增殖和转移,因此在 Bca 发病机制中发挥致癌作用。总之,我们的研究表明,lncARSR 在 Bca 细胞中发挥着关键的调节作用,lncARSR 可能作为膀胱癌的潜在诊断生物标志物和治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/128f/6930381/88aef3f1cc55/ijbsv16p0001g001.jpg

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