Long Noncoding RNA <i>PVT1</i> Promotes Non–Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression

<jats:title>Abstract</jats:title> <jats:p>Long noncoding RNAs (lncRNA) are a novel class of transcripts with no protein coding capacity, but with diverse functions in cancer cell proliferation, apoptosis, and metastasis. The lncRNA PVT1 is 1,716 nt in length and located in the chr8q24.21 region, which also contains the myelocytomatosis (MYC) oncogene. Previous studies demonstrated that MYC promotes PVT1 expression in primary human cancers. However, the expression pattern and potential biologic function of PVT1 in non–small cell lung cancer (NSCLC) is still unclear. Here, we found that PVT1 was upregulated in 105 human NSCLC tissues compared with normal samples. High expression of PVT1 was associated with a higher tumor–node–metastasis stage and tumor size, as well as poorer overall survival. Functional analysis revealed that knockdown of PVT1 inhibited NSCLC cell proliferation and induced apoptosis both in vitro and in vivo. RNA immunoprecipitation and chromatin immunoprecipitation assays demonstrated that PVT1 recruits EZH2 to the large tumor suppressor kinase 2 (LATS2) promoter and represses LATS2 transcription. Furthermore, ectopic expression of LATS2 increased apoptosis and repressed lung adenocarcinoma cell proliferation by regulating the Mdm2-p53 pathway. Taken together, our findings indicated that PVT1/EZH2/LATS2 interactions might serve as new target for lung adenocarcinoma diagnosis and therapy. Mol Cancer Ther; 15(5); 1082–94. ©2016 AACR.</jats:p>