title: MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis.
abstract: BACKGROUND
  MiR-125b functions as an oncogene in many cancers; however, its clinical significance and molecular mechanism in gastric cancers have never been sufficiently investigated. Here, we elucidated the functions and molecular regulated pathways of MiR-125b in gastric cancer.
  
  
  METHODS
  We investigated MiR-125b expression in fresh tissues from 50 gastric cancer patients and 6 gastric cancer cell lines using RT-PCR, and explored its prognostic value by hybridizing MiR-125b in situ for 300 clinical gastric tumor tissues with pathological diagnosis and clinical parameters. The effects of MiR-125b on gastric cancer cells and downstream target genes and proteins were analyzed by MTT, transwell assay, RT-PCR, and western blot on the basis of silencing MiR-125b in vitro. Luciferase reporter plasmid was constructed to demonstrate MiR-125b's direct target.
  
  
  RESULTS
  MiR-125b was upregulated in gastric cancer tissues and cell lines, and significantly promoted cellular proliferation, migration, and invasion by downregulating the expression of PPP1CA and upregulating Rb phosphorylation. MiR-125b expression was significantly correlated with tumor size and depth of invasion, lymph nodes, distant metastasis, and TNM stage. The high-MiR-125b-expression group had a significantly poorer prognosis than the low-expression group (P < 0.05) in stages I, II, and III, and the 5-year survival rate in of the high-expression group was significantly lower than that of the low-expression group.
  
  
  CONCLUSIONS
  MiR-125b functions as an oncogene by targeting downregulated PPP1CA and upregulated Rb phosphorylation in gastric cancer. MiR-125b not only promotes cellular proliferation, migration, and invasion in vitro, but also acts as an independent prognostic factor in gastric cancer.
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wu
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China.
authors.forename: Jin-Jie
authors.initials: JJ
authors.lastname: Wang
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Department of Pathology, Zhejiang Provincal People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Lan
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, People's Republic of China.
authors.forename: Xu-Jun
authors.initials: XJ
authors.lastname: He
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, People's Republic of China.
authors.forename: Hui-Ju
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, People's Republic of China.
authors.forename: Ying-Yu
authors.initials: YY
authors.lastname: Ma
authors.affiliation: Key Laboratory of Gastroenterology of Zhejiang Province, Hangzhou, 310014, People's Republic of China.
authors.forename: Ying-Jie
authors.initials: YJ
authors.lastname: Xia
authors.affiliation: Department of Pathology, Zhejiang Provincal People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Guo-Qing
authors.initials: GQ
authors.lastname: Ru
authors.affiliation: Department of Pathology, Zhejiang Provincal People's Hospital, Hangzhou, 310014, People's Republic of China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pathology, Zhejiang Provincal People's Hospital, Hangzhou, 310014, People's Republic of China. zhaozhongsheng1950@163.com.
authors.forename: Zhong-Sheng
authors.initials: ZS
authors.lastname: Zhao
authors.affiliation: Department of Pathology and Pathophysiology, Zhejiang University School of Medicine, Hangzhou, 310058, People's Republic of China. zhouren@zju.edu.cn.
authors.forename: Ren
authors.initials: R
authors.lastname: Zhou
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement; D049109:Cell Proliferation / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011379:Prognosis; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D046888:Tissue Array Analysis; D014162:Transfection
chemical_list: C531888:MIRN125 microRNA, human; D035683:MicroRNAs; D034741:RNA, Small Interfering; D016160:Retinoblastoma Protein; C517187:PPP1CA protein, human; D054645:Protein Phosphatase 1
keywords: Gastric cancer; MiR-125b; PPP1CA