Long noncoding RNA LINC00336 inhibits ferroptosis in lung cancer by functioning as a competing endogenous RNA

Release time:2020-07-13

Impact Factor:8.371

Affiliation of Author(s):中南大学

Teaching and Research Group:病理学系

Journal:Cell Death Differ

Abstract:The regulatory loop between long noncoding RNAs (lncRNAs) and microRNAs has a dynamic role in transcriptional and translational regulation, and is involved in cancer. However, the regulatory circuitry between lncRNAs and microRNAs in tumorigenesis remains elusive. Here we demonstrate that a nuclear lncRNA LINC00336 is upregulated in lung cancer and functions as an oncogene by acting as a competing endogenous RNA (ceRNAs). LINC00336 bound RNA-binding protein ELAVL1 (ELAV-like RNA-binding protein 1) using nucleotides 1901-2107 of LINC00336 and the RRM interaction domain and key amino acids (aa) of ELAVL1 (aa 101-213), inhibiting ferroptosis. Moreover, ELAVL1 increased LINC00336 expression by stabilizing its posttranscriptional level, whereas LSH (lymphoid-specific helicase) increased ELAVL1 expression through the p53 signaling pathway, further supporting the hypothesis that LSH promotes LINC00336 expression. Interestingly, LINC00336 served as an endogenous sponge of microRNA 6852 (MIR6852) to regulate the expression of cystathionine-β-synthase (CBS), a surrogate marker of ferroptosis. Finally, we found that MIR6852 inhibited cell growth by promoting ferroptosis. These data show that the network of lncRNA and ceRNA has an important role in tumorigenesis and ferroptosis.

Co-author:Chao Mao, Lianlian Ouyang, Yating Liu, Weiwei Lai, Na Liu, Ying Shi,Ling Chen, Desheng Xiao, Fenglei Yu, Xiang Wang, Hu Zhou, Ya Cao, Shuang Liu, Qin Yan

First Author:Min Wang

Indexed by:Journal paper

Correspondence Author:Yongguang Tao, Bin Zhang

Volume:26(11)

Page Number:2329-2343

Translation or Not:no

Date of Publication:2019-11-01

Included Journals:SCI