title: The Long Noncoding RNA MEG3 Contributes to Cisplatin Resistance of Human Lung Adenocarcinoma.
abstract: Long noncoding RNAs (lncRNAs) have been identified as oncogenes or tumor suppressors that are involved in tumorigenesis and chemotherapy drug resistance. Maternally expressed gene 3 (MEG3) is an imprinted gene located at 14q32 that encodes an lncRNA, and decreased MEG3 expression plays an important role in multiple cancers. However, its biological role in the development of the chemoresistance phenotype of human lung adenocarcinoma (LAD) is unknown. This study aimed to observe the expression of MEG3 in LAD and to evaluate its biological role and clinical significance in the resistance of LAD cells to cisplatin. MEG3 expression was markedly decreased in cisplatin-resistant A549/DDP cells compared with parental A549 cells as shown by an lncRNA microarray. MEG3 overexpression in A549/DDP cells increased their chemosensitivity to cisplatin both in vitro and in vivo by inhibiting cell proliferation and inducing apoptosis. By contrast, MEG3 knockdown in A549 cells decreased the chemosensitivity. Moreover, MEG3 was decreased in cisplatin-insensitive LAD tissues while p53 protein levels were decreased and Bcl-xl protein levels increased. Furthermore, patients with lower levels of MEG3 expression showed worse responses to cisplatin-based chemotherapy. These findings demonstrate that MEG3 is significantly downregulated in LAD and partially regulates the cisplatin resistance of LAD cells through the control of p53 and Bcl-xl expression. Thus, MEG3 may represent a new marker of poor response to cisplatin and could be a potential therapeutic target for LAD chemotherapy.
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Li
authors.initials: L
authors.lastname: Wan
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Kaihua
authors.initials: K
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Molecular Biology, Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Medical Oncology, Nanjing Medical University Affiliated Cancer Hospital of Jiangsu Province, Cancer Institution of Jiangsu Province, Nanjing,P.R. China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Pathology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Binbin
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Guojian
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Zhaoxia
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D062085:RNA, Long Noncoding / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; C498907:MEG3 non-coding RNA, human; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D002945:Cisplatin