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Research Paper|Volume 12, Issue 16|pp 16021—16034

Long non-coding RNA DLX6-AS1 facilitates bladder cancer progression through modulating miR-195-5p/VEGFA signaling pathway

Hengbing Wang1, Xiaobing Niu1, Hesong Jiang1, Fei Mao1, Bing Zhong1, Xi Jiang1, Guangbo Fu1
  • 1Department of Urology, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an 223300, Jiangsu Province, China
* Co-first authors
Received: August 12, 2019Accepted: May 22, 2020Published: August 3, 2020
https://doi.org/10.18632/aging.103374

Copyright © 2020 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

In this study, we aim at investigating the expression and regulation role of long non-coding RNA (lncRNA) DLX6-AS1 in bladder cancer (BC). DLX6-AS1 was highly expressed in BC tissues and significant negative correlation with the 5-year survival in the BC patients. The results showed that the proliferation, migration and invasion activities of BC cells were promoted by DLX6-AS1 overexpression, while cell apoptosis was repressed. However, knockdown DLX6-AS1 presented an pposite regulatory effect, and DLX6-AS1 knockdown delayed tumor in vivo. The potential target of DLX6-AS1 in BC was predicted and verified by RIP, RNA pull-down, and dual-luciferase reporter assays as miR-195-5p. The results showed that miR-195-5p was down-regulated in BC tissues, the expression of which was significantly negative correlated with DLX6-AS1 expression. In addition, the results also showed that miR-195-5p targeted and down-regulated the VEGFA. Knockdown of DLX6-AS1 up-regulated miR-195-5p expression and down-regulated VEGFA expression. Moreover, down-regulation of VEGFA expression caused by DLX6-AS1 inhibited phosphorylation of Raf-1, MEK1/2, and ERK1/2, while miR-195-5p inhibitors abolished the effect of silencing DLX6-AS1 expression. Our study demonstrated that DLX6-AS1 played an oncogenic role in BC through miR-195-5p-mediated VEGFA/Ras/Raf/MEK/ERK pathway.