LncRNA SPRY4-IT1 sponges miR-101-3p to promote proliferation and metastasis of bladder cancer cells through up-regulating EZH2*
LncRNA SPRY4-IT1 sponges miR-101-3p to promote proliferation and metastasis of bladder cancer cells through up-regulating EZH2*
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LncRNA SPRY4-IT1 海绵 miR-101-3p 通过上调 EZH2 促进膀胱癌细胞的增殖和转移。
DOI：
10.1016/j.canlet.2016.12.005
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发表时间：
2017-03-01
期刊：
影响因子：
9.7
通讯作者：
Jiang, Guosong
中科院分区：
文献类型：
--
作者：
Liu, Dong;Li, Yawei;Jiang, Guosong
越来越多的证据表明，长链非编码RNA（LncRNA）在肿瘤的发生、发展中起着重要作用。先前的研究表明，SPRY4-IT1的过表达预示着预后不良，并促进了几种癌症的肿瘤进展。然而，SPRY 4-IT 1在膀胱癌中的潜在机制仍然未知。在本研究中，我们发现SPRY4-IT1基因敲低可抑制膀胱癌细胞的增殖、迁移和侵袭能力，并促进膀胱癌细胞的凋亡。从机制上讲，SPRY4-IT1的敲低增加了miR-101 - 3p的表达，随后在转录后水平抑制了EZH2的表达。重要的是，SPRY4-IT1可以直接与miR-101 - 3p相互作用，并且miR-101 - 3p的下调有效地逆转了SPRY4-IT1 shRNA诱导的EZH2抑制。因此，SPRY4-IT1通过海绵样作用于miR-101 - 3p，正调控EZH2的表达，在膀胱癌的发生发展中发挥致癌作用。总之，我们的研究阐明了LncRNA SPRY4-IT1作为膀胱癌中miRNA海绵的作用，并为膀胱癌中LncRNA指导的诊断和治疗提供了新的见解。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Emerging evidences have indicated that long non-coding RNAs (LncRNAs) play vital roles in cancer development and progression. Previous studies have suggested that overexpression of SPRY4-IT1 predicates poor prognosis and promotes tumor progress in several cancers. However, the underlying mechanism of SPRY4-IT1 in bladder cancer remains unknown. In this study, we found that SPRY4-IT1 knockdown induced inhibition of cell proliferation, cell migration and invasion ability, and caused promotion of apoptosis in bladder cancer both in vitro and in vivo. Mechanistically, knockdown of SPRY4-IT1 increased the expression of miR-101-3p and subsequently inhibited the expression of EZH2 at posttranscriptional level. Importantly, SPRY4-IT1 could directly interact with miR-101-3p and down regulation of miR-101-3p efficiently reversed the suppression of EZH2 induced by SPRY4-IT1 shRNA. Thus, SPRY4-IT1 positively regulated the expression of EZH2 through sponging miR-101-3p, and played an oncogenic role in bladder cancer progression. Together, our study elucidates the role of LncRNA SPRY4-IT1 as a miRNA sponge in bladder cancer, and sheds new light on LncRNA-directed diagnostics and therapeutics in bladder cancer. (C) 2016 Elsevier Ireland Ltd. All rights reserved.