Long non-coding RNA PVT1 promotes non-small cell lung cancer cell proliferation through epigenetically regulating LATS2 expression

Long non-coding RNAs (lncRNAs) 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 1716 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 biological function of PVT1 in non-small cell lung cancer (NSCLC) is still unclear. Here we found that PVT1 was up-regulated in 105 human NSCLC tissues compared with normal samples. High expression of PVT1 was associated with a higher TNM 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 (RIP) and Chromatin immunoprecipitation (ChIP) 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 LAD cell proliferation by regulating the Mdm2-p53 pathway. Taken together, our findings indicated that PVT1/EZH2/LATS2 interactions might serve as new target for LAD diagnosis and therapy.

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