title: MiR-143 Targeting TAK1 Attenuates Pancreatic Ductal Adenocarcinoma Progression via MAPK and NF-κB Pathway In Vitro.
abstract: Transforming growth factor (TGF)-β-activated kinase 1 (TAK1) is one of the major regulators of inflammation-induced cancer cell growth and progression. MiR-143 dysregulation is a common event in a variety of human diseases including pancreatic ductal adenocarcinoma (PDA).
  
  
  
  To identify the interaction between TAK1 and miR-143 in PDA.
  
  
  
  Data mining of TAK1 expression in PDA patient gene profiling was conducted. QRT-PCR and western blot were performed to detect the expression of TAK1 in PDA tissues and cell lines. Ectopic miR-143 and TAK1 were introduced to PDA cells. Cell growth, apoptosis and migration were examined. Xenograft models were used to examine the function of TAK1 in vivo. Western blot and luciferase assay were carried out to investigate the direct target of miR-143.
  
  
  
  PDA patient gene profiling data (GSE15471 and GSE16515) showed that TAK1 mRNA was aberrantly up-regulated in PDA tissues. TAK1 protein levels were overexpressed in PDA tissues and cell lines. Overexpression of TAK1 was strongly associated with positive lymph node metastasis. Inhibition of TAK1 suppressed cell growth, migration, and induced cell apoptosis in vitro and in vivo. Further studies demonstrated that TAK1 was a direct target gene of miR-143. MiR-143 also inhibited PDA cells proliferation and migration, induced apoptosis and G1/S arrest. Moreover, TAK1 depletion inactivated MAPK and NF-κB pathway, mimicking the function of miR-143.
  
  
  
  The study highlights that miR-143 acts as a tumor suppressor in PDA through directly targeting TAK1, and their functional regulation may provide potential therapeutic strategies in clinics.
authors.affiliation: Department of Gastroenterology and Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China.
authors.forename: Feng-Ting
authors.initials: FT
authors.lastname: Huang
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China.
authors.forename: Juan-Fei
authors.initials: JF
authors.lastname: Peng
authors.affiliation: Department of Ultrasound, the Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong Province, People's Republic of China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China.
authors.forename: Yan-Yan
authors.initials: YY
authors.lastname: Zhuang
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China.
authors.forename: Chu-Qiang
authors.initials: CQ
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, the Sixth Affiliated Hospital, Sun Yat-sen University, No. 26 Yuancun Erheng Road, Guangzhou, 510655, Guangdong Province, People's Republic of China.
authors.forename: Jian
authors.initials: J
authors.lastname: Tang
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China.
authors.forename: Yuan-Hua
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Gastroenterology and Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, No. 107 Yanjiang West Road, Guangzhou, 510120, Guangdong Province, People's Republic of China. shinengz@hotmail.com.
authors.forename: Shi-Neng
authors.initials: SN
authors.lastname: Zhang
mesh_terms: D000368:Aged; D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D014408:Biomarkers, Tumor; D020930:MAP Kinase Kinase Kinases; D035683:MicroRNAs; D016328:NF-kappa B; D000099151:MAP Kinase Kinase Kinase 7; C542359:MIRN143 microRNA, human
keywords: MAPK; MiR-143; NF-κB; Pancreatic ductal adenocarcinoma; TAK1