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Downregulation of microRNA-193-3p inhibits tumor proliferation migration and chemoresistance in human gastric cancer by regulating PTEN gene

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Tumor Biology

Abstract

In this study, we investigated the functional mechanisms of microRNA-193-3p (miR-193-3p) in human gastric cancer. Quantitative RT-PCR (qRT-PCR) was used to assess whether miR-193-3p was aberrantly expressed in gastric cancer cells and clinical samples from gastric cancer patients. Gastric cancer cell line AGS and MKN-45 cells were stably transduced with lentivirus to downregulate endogenous miR-193-3p. The modulation of miR-193-3p downregulation on gastric cancer proliferation, migration, chemo-drug responses, and tumor explant were assessed by MTT, wound-healing, 5-FU chemoresistance and in vivo tumorigenicity assays, respectively. Downstream target of miR-193-3p, phosphatase and tensin homolog (PTEN) in gastric cancer, was assessed by dual-luciferase reporter assay, qRT-PCR, and western blot. PTEN was knocked down by siRNA in AGS and MKN-45 cells to assess its direct impact on miR-193-3p modulation in gastric cancer. MiR-193-3p was aberrantly upregulated in both gastric cell lines and human gastric tumors. In AGS and MKN-45 cells, miR-193-3p downregulation reduced cancer proliferation, migration and 5-FU chemoresistance in vitro, and tumorigenicity in vivo. PTEN was confirmed to be targeted by miR-193-3p in gastric cancer. PTEN inhibition in AGS and MKN-45 cells directly reversed the anti-tumor modulations of miR-193-3p downregulation on gastric cancer proliferation, migration, and 5-FU chemoresistance. We presented clear evidence showing miR-193-3p played critical role in regulating human gastric cancer through direct targeting on PTEN gene.

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Authors and Affiliations

  1. Department of Gastrointestinal surgery, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Chongqing, 402160, China

    Bin Jian, Zhongfu Li, Dachun Xiao, Gan He, Lian Bai & Qiang Yang

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  1. Bin Jian
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  2. Zhongfu Li
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  3. Dachun Xiao
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  4. Gan He
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  5. Lian Bai
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  6. Qiang Yang
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Correspondence to Zhongfu Li.

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Jian, B., Li, Z., Xiao, D. et al. Downregulation of microRNA-193-3p inhibits tumor proliferation migration and chemoresistance in human gastric cancer by regulating PTEN gene. Tumor Biol. 37, 8941–8949 (2016). https://doi.org/10.1007/s13277-015-4727-x

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  • DOI: https://doi.org/10.1007/s13277-015-4727-x

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