The long noncoding RNA LINC01207 promotes proliferation of lung adenocarcinoma

Am J Cancer Res. 2015 Sep 15;5(10):3162-73. eCollection 2015.

Abstract

Lung adenocarcinoma (LAD) and lung squamous cell cancer (LSCC) are two most common histological types of lung cancer, while they differ in many aspects. Recent evidence shows that long non-coding RNAs (lncRNAs) play an important role in the process of cancer initiation and progression. Thus, characterization of LAD and LSCC associated lncRNAs may help understand the difference between LAD and LSCC. Here, we analyzed three sets of RNA-seq data, including LAD RNA-seq data from TCGA project. We identified a novel lncRNA, long intergenic non-protein coding RNA 1207 (LINC01207) which was significantly up-regulated in LAD tissues compared with paired non-tumor tissues (5.78 fold increase, P<0.05), while there was no significant differences between LSCC tissues and adjacent non-tumor tissues. The expression level of LINC01207 was associated with TNM stage of LAD patients, and higher LINC01207 level indicated advanced TNM stage (P<0.05) and shorter survival (HR=2.53, P<0.05). By small interfering RNA (siRNA) mediated knockdown of LINC01207, we determined the biological function of LINC01207 in A549 cell line. After knockdown of LINC01207, cell proliferation ability was inhibited. Further analysis showed that after silence of LINC01207, the percentage of apoptotic cells significantly increased. By RNA immunoprecipitation and Chromatin immunoprecipitation assay, we demonstrated that LINC01207 could bind with EZH2 and mediated trimethylation of histone 3 lysine 27 at the promoter region of Bad, an important pro-apoptotic gene. Finally, we developed xenograft tumor models in nude mice and xenograft tumors derived from A549 cells transfected with siRNA-LINC01207 had significantly lower tumor weight and smaller tumor volume. In summary, the novel lncRNA, LINC01207 is specifically up-regulated in LAD but not in LSCC; and LINC01207 could promote LAD cell growth both in vivo and in vitro.

Keywords: LINC01207; Lung cancer; apoptosis; bad; lung adenocarcinoma.