title: Downregulation of microRNA-193-3p inhibits tumor proliferation migration and chemoresistance in human gastric cancer by regulating PTEN gene.
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.
authors.affiliation: Department of Gastrointestinal surgery, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Chongqing, 402160, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Jian
authors.affiliation: Department of Gastrointestinal surgery, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Chongqing, 402160, China. zhongfu2@aol.com.
authors.forename: Zhongfu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Gastrointestinal surgery, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Chongqing, 402160, China.
authors.forename: Dachun
authors.initials: D
authors.lastname: Xiao
authors.affiliation: Department of Gastrointestinal surgery, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Chongqing, 402160, China.
authors.forename: Gan
authors.initials: G
authors.lastname: He
authors.affiliation: Department of Gastrointestinal surgery, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Chongqing, 402160, China.
authors.forename: Lian
authors.initials: L
authors.lastname: Bai
authors.affiliation: Department of Gastrointestinal surgery, Yongchuan Hospital, Chongqing Medical University, 439 Xuanhua Road, Chongqing, 402160, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Yang
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000469:parasitology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D035683:MicroRNAs; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D005472:Fluorouracil
keywords: Gastric cancer; Migration; PTEN; Proliferation; miR-193-3p