Long noncoding RNA LINC00337 accelerates the non-small-cell lung cancer progression through inhibiting TIMP2 by recruiting DNMT1

Am J Transl Res. 2019 Sep 15;11(9):6075-6083. eCollection 2019.

Abstract

Accumulating evidence reveals the essential roles of long noncoding RNAs (lncRNAs) in the non-small-cell lung cancer (NSCLC) tumorigenesis. Here, our research investigated the biological roles of novel lncRNA LINC00337 in the NSCLC tumorigenesis and discover the potential mechanism. In the NSCLC tissue and cell lines, LINC00337 was found to be remarkedly up-regulated, and the ectopic LINC00337 overexpression indicated the poor survival of NSCLC patients. In vitro, gain and loss of functional assays showed that LINC00337 promoted the progression of NSCLC cells, including proliferation and invasion. In vivo, LINC00337 knockdown inhibited the tumor growth of NSCLC cells. Mechanically, LINC00337 could recruit the epigenetic repressor DNMT1 to the promoter region of TIMP2 to silence its expression. In conclusion, our study found the critical regulation of lncRNA LINC00337 for the NSCLC through epigenetic regulation, which may serve as a predictive biomarker and potential therapeutic target.

Keywords: DNMT1; LINC00337; NSCLC; TIMP2; promoter methylation.