Long non-coding RNA MEG3 inhibits NSCLC cells proliferation and induces apoptosis by affecting p53 expression
| Autor: | Ming Sun, Wei-ping Xie, Wei Li, Wei-qin Wu, Meiling Zhang, Ya-yi Hou, Kaihua Lu, Xiang-hua Liu |
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| Rok vydání: | 2013 |
| Předmět: |
p53
Male Cancer Research Lung Neoplasms Proliferation Bisulfite sequencing Apoptosis NSCLC medicine.disease_cause Mice Carcinoma Non-Small-Cell Lung Cell Line Tumor Genetics medicine Animals Humans MEG3 Cell Proliferation Neoplasm Staging biology Cell growth Cancer DNA Methylation medicine.disease respiratory tract diseases Gene Expression Regulation Neoplastic Disease Models Animal Cell Transformation Neoplastic Oncology Tumor progression Lymphatic Metastasis Long non-coding RNA DNA methylation biology.protein Cancer research Mdm2 Female RNA Long Noncoding Neoplasm Grading Tumor Suppressor Protein p53 Carcinogenesis Research Article |
| Zdroj: | BMC Cancer |
| ISSN: | 1471-2407 |
| DOI: | 10.1186/1471-2407-13-461 |
| Popis: | Background Long non-coding RNAs play an important role in tumorigenesis, hence, identification of cancer-associated lncRNAs and investigation of their biological functions and molecular mechanisms are important for understanding the development and progression of cancer. Recently, the downregulation of lncRNA MEG3 has been observed in various human cancers. However, its role in non-small cell lung cancer (NSCLC) is unknown. The aim of this study was to examine the expression pattern of MEG3 in NSCLC and to evaluate its biological role and clinical significance in tumor progression. Methods Expression of MEG3 was analyzed in 44 NSCLC tissues and 7 NSCLC cell lines by qRT-PCR. Over-expression approaches were used to investigate the biological functions of MEG3 in NSCLC cells. Bisulfite sequencing was used to investigate DNA methylation on MEG3 expression. The effect of MEG3 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by Hoechst staining and Flow-cytometric analysis. NSCLC cells transfected with pCDNA-MEG3 were injection into nude mice to study the effect of MEG3 on tumorigenesis in vivo . Protein levels of MEG3 targets were determined by western blot analysis. Differences between groups were tested for significance using Student’s t-test (two-tailed). Results MEG3 expression was decreased in non-small cell lung cancer (NSCLC) tumor tissues compared with normal tissues, and associated with advanced pathologic stage, and tumor size. Moreover, patients with lower levels of MEG3 expression had a relatively poor prognosis. Overexpression of MEG3 decreased NSCLC cells proliferation and induced apoptosis in vitro and impeded tumorigenesis in vivo. MDM2 and p53 protein levels were affected by MEG3 over-expression in vitro. Conclusions Our findings indicate that MEG3 is significantly down-regulated in NSCLC tissues that could be affected by DNA methylation, and regulates NSCLC cell proliferation and apoptosis, partially via the activition of p53. Thus, MEG3 may represent a new marker of poor prognosis and is a potential therapeutic target for NSCLC intervention. |
| Databáze: | OpenAIRE |
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