Erschienen in:
13.02.2017 | Original Article
MiR-143 Targeting TAK1 Attenuates Pancreatic Ductal Adenocarcinoma Progression via MAPK and NF-κB Pathway In Vitro
verfasst von:
Feng-Ting Huang, Juan-Fei Peng, Wen-Jie Cheng, Yan-Yan Zhuang, Ling-Yun Wang, Chu-Qiang Li, Jian Tang, Wen-Ying Chen, Yuan-Hua Li, Shi-Neng Zhang
Erschienen in:
Digestive Diseases and Sciences
|
Ausgabe 4/2017
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Abstract
Background
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).
Aims
To identify the interaction between TAK1 and miR-143 in PDA.
Methods
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.
Results
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.
Conclusions
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.