Silencing of Long Noncoding RNA <i>MIR22HG</i> Triggers Cell Survival/Death Signaling via Oncogenes YBX1, MET, and p21 in Lung Cancer.

Abstract

The long noncoding RNA (lncRNA) <i>MIR22HG</i> has previously been identified as a prognostic marker in hepatocellular carcinoma. Here, we performed a comprehensive analysis of lncRNA expression profiles from RNA-Seq data and report that <i>MIR22HG</i> plays a similar role in lung cancer. Analysis of 918 lung cancer and normal lung tissues and lung cancer cell lines revealed that <i>MIR22HG</i> was significantly downregulated in lung cancer; this decreased expression was associated with poor patient survival. <i>MIR22HG</i> bound and stabilized the YBX1 protein. Silencing of <i>MIR22HG</i> triggered both cell survival and cell death signaling through dysregulation of the oncogenes YBX1, MET, and p21. In this <i>MIR22HG</i> network, p21 played an oncogenic role by promoting cell proliferation and antiapoptosis in lung cancers. <i>MIR22HG</i> played a tumor-suppressive role as indicated by inhibition of multiple cell cycle-related genes in human primary lung tumors. These data show that <i>MIR22HG</i> has potential as a new diagnostic and prognostic marker and as a therapeutic target for lung cancer.<b>Significance:</b> The lncRNA <i>MIR22HG</i> functions as a tumor suppressor, with potential use a diagnostic/prognostic marker and therapeutic target in lung cancer. <i>Cancer Res; 78(12); 3207-19. ©2018 AACR</i>.