title: Downregulation of Meg3 enhances cisplatin resistance of lung cancer cells through activation of the WNT/β-catenin signaling pathway.
abstract: Maternally expressed gene 3 (Meg3) has been shown to promote tumor progression. However, the role of Meg3 in the development of a chemoresistant phenotype of human lung cancer has remains. Reverse transcription‑quantitative polymerase chain reaction analysis was used to determine the expression of Meg3. Flow cytometric analysis and MTT assay were also used to investigate the cell cycle and apoptosis. The present study detected that the expression levels of Meg3 were significantly lower in cisplatin‑resistant A549/DDP lung cancer cells, compared with those in parental A549 cells. Furthermore, upregulation of Meg3 was able to re‑sensitize the A549/DDP cells to cisplatin in vitro. Whereas downregulation of Meg3, by RNA interference, decreased the sensitivity of A549 cells to cisplatin. The results of the present study also demonstrated that the Meg3‑mediated chemosensitivity enhancement was associated with the induction of cell-cycle arrest and increased apoptosis, through regulation of p53, β‑catenin and survivin, which is a target gene of the WNT/β‑catenin signaling pathway. In conclusion, these results suggested that Meg3 may have a crucial role in the development of cisplatin resistance in non-small cell lung cancer.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xia
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Zhicheng
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Pengli
authors.initials: P
authors.lastname: Wang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Yijiang
authors.initials: Y
authors.lastname: Chen
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D062085:RNA, Long Noncoding / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; C495270:CTNNB1 protein, human; D051034:Inhibitor of Apoptosis Proteins; C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; D034741:RNA, Small Interfering; D000077022:Survivin; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; D002945:Cisplatin