title: Interaction between microRNA-181a and TNFAIP1 regulates pancreatic cancer proliferation and migration.
abstract: We investigated the role of microRNA 181a (miR-181a) and its downstream target tumor necrosis factor, alpha-induced protein 1 (TNFAIP1) in pancreatic cancer regulation. Quantitative real-time PCR (qRT-PCR) was applied to evaluate the gene expression of miR-181a in seven pancreatic cancer cell lines. MiR-181a inhibitor lentivirus (miR-181a-IN) was used to down-regulate miR-181a in Capan-1 and AsPC-1 cells. The effects of miR-181a down-regulation on pancreatic cancer were evaluated by in vitro proliferation assay and migration assay. Targeting of miR-181a on TNFAIP1 in pancreatic cancer was evaluated by dual-luciferase reporter assay and western blot. TNFAIP1 was either upregulated by pcDNA3.1 (+) expression vector or down-regulated by siRNA in Capan-1 and AsPC-1 cells. The subsequent effects of TNFAIP1 upregulation or down-regulation on miR-181a mediated pancreatic cancer regulation were also evaluated through in vitro proliferation and migration assays. The in vivo effect of miR-181a down-regulation on pancreatic tumor growth was evaluated by a xenograft assay. MiR-181a was consistently upregulated in pancreatic cancer cell lines. MiR-181a down-regulation inhibited proliferation and migration in vitro, and upregulated TNFAIP1 in pancreatic cancer cells. Ectopic TNFAIP1 overexpression had similar tumor-suppressive effects on pancreatic cancer proliferation and migration as miR-181a down-regulation, whereas siRNA-mediated TNFAIP1 down-regulation had opposite or oncogenic effects on pancreatic cancer. In vivo pancreatic xenograft showed miR-181a recapitulated the in vitro anti-tumor effects and its regulation on TNFAIP1. MiR-181a played a critical role in regulating pancreatic cancer growth and migration, likely interacting with TNFAIP1.
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Er Rd, Guangzhou, 510080, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Er Rd, Guangzhou, 510080, China.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Guo
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Er Rd, Guangzhou, 510080, China.
authors.forename: Ronglin
authors.initials: R
authors.lastname: Hu
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Er Rd, Guangzhou, 510080, China.
authors.forename: Xiaoshun
authors.initials: X
authors.lastname: He
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Er Rd, Guangzhou, 510080, China. jiaoxingyuan@hotmail.com.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Jiao
authors.affiliation: Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Er Rd, Guangzhou, 510080, China. 740803277@qq.com.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zhu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C540193:MIrn181 microRNA, human; D035683:MicroRNAs; D011506:Proteins; D034741:RNA, Small Interfering; C115968:TNFAIP1 protein, human; D014409:Tumor Necrosis Factor-alpha
keywords: Migration; Pancreatic cancer; TNFAIP1; Tumor proliferation; miR-181a