GIAT4RA functions as a tumor suppressor in non-small cell lung cancer by counteracting Uchl3-mediated deubiquitination of LSH

Release time:2020-07-13

Impact Factor:7.971

Affiliation of Author(s):中南大学

Teaching and Research Group:病理学系

Journal:Oncogene

Abstract:Elucidating mechanisms in tumor suppressors and epigenetic modifiers are needed to gain insights into the etiology and treatment of cancer, the interplay between long intergenic non-coding RNAs (lncRNAs) and chromatin remodeling remains unclear. Here, we showed that GIAT4RA, a poorly characterized lncRNA LOC102723729, was significantly decreased in lung cancer cells and tissues; while no association was observed with clinical risk factors, expression was linked with clinical stage and lymphatic metastasis. Higher expression of GIAT4RA was linked with overall survival in NSCLC. GIAT4RA inhibited many characteristics of tumorigenesis including cell growth, clonal formation, migration and invasion, epithelial-mesenchymal transition, tumor sphere and tumor growth in vivo. Mechanistically, GIAT4RA was essential for the degradation of chromatin modifier lymphoid-specific helicase (LSH) by counteracting the deubiquintination in proteasome pathway by binding to 227-589 AA of LSH. GIAT4RA interfered with ubiquitin hydrolase Uchl3-mediated interaction and stabilization of LSH. LSH knockdown rescued GIAT4RA-promoted features, and LSH overexpression prevented GIAT4RA-induced phenotypes. Taken together, lncRNA GIAT4RA plays a critical role in NSCLC adenocarcinoma as a ubiquitination regulator and tumor suppressor.

Co-author:Na Liu, Ling Chen, Yiqun Jiang, Ying Shi, Chao Mao, Yating Liu, Min Wang, Weiwei Lai, Haosheng Tang, Menghui Gao, Desheng Xiao, Xiang Wang, Hu Zhou, Can-e Tang, Wenliang Liu, Fenglei Yu, Ya Cao, Qin Yan

First Author:Rui Yang

Indexed by:Journal paper

Correspondence Author:Shuang Liu, Yongguang Tao

Volume:38(46)

Page Number:7133-7145

Translation or Not:no

Date of Publication:2019-08-15

Included Journals:SCI