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Interaction between microRNA-181a and TNFAIP1 regulates pancreatic cancer proliferation and migration

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Tumor Biology

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.

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Conflicts of interest

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Funding

This work was funded by the National Natural Science Foundation of China (No. 81270531) and Doctoral Program Foundation of Institutions of Higher Education of China (No. 20120171110073).

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Authors and Affiliations

  1. Organ Transplant Center, The First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Er Rd, Guangzhou, 510080, China

    Peng Zhang, Zhiyong Guo, Ronglin Hu, Xiaoshun He, Xingyuan Jiao & Xiaofeng Zhu

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  1. Peng Zhang
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  2. Zhiyong Guo
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  3. Ronglin Hu
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  4. Xiaoshun He
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  5. Xingyuan Jiao
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  6. Xiaofeng Zhu
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Correspondence to Xingyuan Jiao or Xiaofeng Zhu.

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Zhang, P., Guo, Z., Hu, R. et al. Interaction between microRNA-181a and TNFAIP1 regulates pancreatic cancer proliferation and migration. Tumor Biol. 36, 9693–9701 (2015). https://doi.org/10.1007/s13277-015-3704-8

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  • DOI: https://doi.org/10.1007/s13277-015-3704-8

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