title: MicroRNA-377 predicts poor clinical outcome of gastric cancer and induces tumorigenesis by targeting multiple tumor-suppressor genes.
abstract: Gastric cancer (GC) is a major cause of cancer mortality worldwide. MicroRNAs are evolutionally conserved small non-coding RNAs that are critical for the regulation of gene expression. The aberrant expression of microRNA (miRNA) is involved in tumorigenesis and prognosis. In the present study, the clinical significance of miR-377 was assessed using RT-qPCR and MTT assay. The results showed that the expression of miR-377 was upregulated in GC compared with normal gastric tissues, and its expression level was increased in GC cell lines compared with normal gastric cells. In addition, there was a significant association between miR-377 expression and clinicopathological characteristics, in particular distant metastasis, TNM stage and early recurrence. GC patients with a higher miR-377 expression showed significantly poorer overall survival (OR) and shorter time to recurrence than those with a lower miR-377 expression. The Cox regression analysis identified miR-377 overexpression as an independent prognostic factor for GC. Overexpression of miR-377 in MKN-45 GC cells significantly promoted cell proliferation, whereas the suppression of miR-377 inhibited these effects. Furthermore, miR-377 downregulated p53, PTEN and TIMP1 expression by directly targeting the 3'-untranslated region of these target genes. Collectively, miR-377 potentially served as a new molecular predictive biomarker of GC tumorigenesis and prognosis, which may be useful in targeted therapy and the prognosis of GC patients.
authors.affiliation: Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Wen
authors.affiliation: Department of Medical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, P.R. China.
authors.forename: Jian-Qiu
authors.initials: JQ
authors.lastname: Wu
authors.affiliation: Department of Medical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Peng
authors.affiliation: Department of Medical Oncology, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, P.R. China.
authors.forename: Ji-Feng
authors.initials: JF
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Nanjing Medical University Affiliated Cancer Hospital, Cancer Institute of Jiangsu Province, Nanjing 210009, P.R. China.
authors.forename: Jin-Hai
authors.initials: JH
authors.lastname: Tang
mesh_terms: D000368:Aged; D063646:Carcinogenesis; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis* / Q000235:genetics; D011379:Prognosis; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C534063:MIRN377 microRNA, human; D035683:MicroRNAs; C560822:TIMP1 protein, human; C495901:TP53 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human