| Literature DB >> 31417184 |
Rui Yang1,2, Na Liu1,2, Ling Chen1,2, Yiqun Jiang1,2,3, Ying Shi1,2, Chao Mao1,2, Yating Liu1,2, Min Wang1,2, Weiwei Lai1,2, Haosheng Tang1,2, Menghui Gao1,2, Desheng Xiao3, Xiang Wang4, Hu Zhou5, Can-E Tang6, Wenliang Liu4, Fenglei Yu4, Ya Cao1,2, Qin Yan7, Shuang Liu8, Yongguang Tao9,10,11.
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.Entities:
Mesh：
Substances：
Year: 2019 PMID： 31417184 DOI： 10.1038/s41388-019-0909-0
Source DB: PubMed Journal: Oncogene ISSN： 0950-9232 Impact factor: 9.867