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Long Noncoding RNA PVT1 Promotes Non-Small Cell Lung Cancer Cell Proliferation through Epigenetically Regulating LATS2 Expression.
- Source :
-
Molecular cancer therapeutics [Mol Cancer Ther] 2016 May; Vol. 15 (5), pp. 1082-94. Date of Electronic Publication: 2016 Feb 23. - Publication Year :
- 2016
-
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.<br /> (©2016 American Association for Cancer Research.)
- Subjects :
- Aged
Aged, 80 and over
Animals
Apoptosis genetics
Carcinoma, Non-Small-Cell Lung diagnosis
Carcinoma, Non-Small-Cell Lung mortality
Cell Cycle Checkpoints genetics
Cell Line, Tumor
Cell Proliferation genetics
Cell Survival genetics
Cell Transformation, Neoplastic
Disease Models, Animal
Female
Gene Knockdown Techniques
Humans
Lung Neoplasms diagnosis
Lung Neoplasms mortality
Male
Mice
Middle Aged
Neoplasm Grading
Neoplasm Metastasis
Neoplasm Staging
Prognosis
Promoter Regions, Genetic
Protein Binding
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins c-mdm2 metabolism
Signal Transduction
Survival Analysis
Tumor Suppressor Protein p53 metabolism
Tumor Suppressor Proteins metabolism
Xenograft Model Antitumor Assays
Carcinoma, Non-Small-Cell Lung genetics
Epigenesis, Genetic
Gene Expression Regulation, Neoplastic
Lung Neoplasms genetics
Protein Serine-Threonine Kinases genetics
RNA, Long Noncoding genetics
Tumor Suppressor Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1538-8514
- Volume :
- 15
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular cancer therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 26908628
- Full Text :
- https://doi.org/10.1158/1535-7163.MCT-15-0707