title: Long noncoding RNA MIR31HG exhibits oncogenic property in pancreatic ductal adenocarcinoma and is negatively regulated by miR-193b.
abstract: Long noncoding RNAs (lncRNAs) play important regulatory roles in a variety of diseases, including many tumors. However, the functional roles of these transcripts and mechanisms responsible for their deregulation in pancreatic ductal adenocarcinoma (PDAC) are not thoroughly understood. In this study, we discovered that lncRNA MIR31HG is markedly upregulated in PDAC. Knockdown of MIR31HG significantly suppressed PDAC cell growth, induced apoptosis and G1/S arrest, and inhibited invasion, whereas enhanced expression of MIR31HG had the opposite effects. Online database analysis tools showed that miR-193b could target MIR31HG and we found an inverse correlation between MIR31HG and miR-193b in PDAC specimens. Inhibition of miR-193b expression significantly upregulated the MIR31HG level, while overexpression of miR-193b suppressed MIR31HG's expression and function, suggesting that MIR31HG is negatively regulated by miR-193b. Moreover, using luciferase reporter and RIP assays, we provide evidence that miR-193b directly targeted MIR31HG by binding to two microRNA binding sites in the MIR31HG sequence. On the other hand, MIR31HG may act as an endogenous 'sponge' by competing for miR-193b binding to regulate the miRNA targets. Collectively, these results demonstrate that MIR31HG functions as an oncogenic lncRNA that promotes tumor progression, and miR-193b targets not only protein-coding genes but also the lncRNA, MIR31HG.
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: P
authors.initials: P
authors.lastname: Liu
authors.affiliation: The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: The State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: X
authors.initials: X
authors.lastname: Peng
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Lu
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: S
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Meng
authors.affiliation: Department of Pathology, Institute of Basic Medical Sciences and School of Basic Medicine, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: W-M
authors.initials: WM
authors.lastname: Tong
authors.affiliation: Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: J
authors.initials: J
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009857:Oncogenes / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D034622:RNA Interference; D062085:RNA, Long Noncoding / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014183:Transplantation, Heterologous
chemical_list: C546818:MIRN193 microRNA, human; D035683:MicroRNAs; D062085:RNA, Long Noncoding; C000622485:long noncoding RNA MIR31HG, human