title: Long Noncoding RNA PVT1 Promotes Non-Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression.
abstract: 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.
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China. Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Guo-Jian
authors.initials: GJ
authors.lastname: Liu
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Chen-Chen
authors.initials: CC
authors.lastname: Wei
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Er-Bao
authors.initials: EB
authors.lastname: Zhang
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Rong
authors.initials: R
authors.lastname: Kong
authors.affiliation: Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China.
authors.forename: Tong-Peng
authors.initials: TP
authors.lastname: Xu
authors.affiliation: Department of Oncology, Huai'an First People's Hospital, Nanjing Medical University, Huai'an, People's Republic of China.
authors.forename: Ming-De
authors.initials: MD
authors.lastname: Huang
authors.affiliation: Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, People's Republic of China. zhaoxiawang88@hotmail.com.
authors.forename: Zhao-Xia
authors.initials: ZX
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D008297:Male; D051379:Mice; D008875:Middle Aged; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D051736:Proto-Oncogene Proteins c-mdm2 / Q000378:metabolism; D062085:RNA, Long Noncoding / Q000235:genetics*; D015398:Signal Transduction; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: C521123:PVT1 long-non-coding RNA, human; D062085:RNA, Long Noncoding; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051736:Proto-Oncogene Proteins c-mdm2; C406449:LATS2 protein, human; D017346:Protein Serine-Threonine Kinases