title: MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation.
abstract: OBJECTIVE
  Uncontrolled proliferation is a key characteristic of gastric carcinogenesis and the precise mechanisms underlying the altered proliferation behaviors of GC cells have not been clearly elucidated. miRNAs has been suggested to play a crucial role in the pathogenesis and development of various cancers. In the present study, we employed an impedance-based real-time cell electronic sensing (RT-CES) system to detect the effects of ectopically expressed miRNAs on GC cell proliferation.
  
  
  METHODS
  miRNA mimics were transfected into gastric cancer cell line SGC7901 and the effect of individual miRNA on the proliferation rate of the cells was measured by the RT-CES system. The screening results were validated with qRT-PCR and miR-137 was selected for further research. The effects of ectopically expressed miR-137 on GC cell growth and cell cycle progress were measured using MTT assay and flow cytometry. The target gene of miR-137 was predicted using different bioinformatics tools and the direct interaction between miR-137 and the 3'-UTR was confirmed with a luciferase reporter assay. The in vivo effect of miR-137 on GC cell proliferation was examined with a tumor-bearing nude mouse model. The correlation between miR-137 expression and patients' prognosis was explored in a cohort of 38 patients. Prognosis was explored in a cohort of 38 patients.
  
  
  RESULTS
  Ectopic expression of miR-137 was sufficient to inhibit GC cell proliferation both in vitro and in vivo. Bioinformatics prediction and luciferase reporter assay revealed CDK6 as a target gene through which miR-137 exerted an inhibitory function. Moreover, miR-137 expression positively correlated with better prognosis.
  
  
  CONCLUSIONS
  Our data indicated an important regulatory role of miR-137 in GC cell proliferation and that it may be explored as a prognostic marker for GC.
authors.affiliation: State Key Laboratory of Cancer Biology, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Xiushan
authors.initials: X
authors.lastname: Zheng
authors.forename: Jiaqiang
authors.initials: J
authors.lastname: Dong
authors.forename: Taiqian
authors.initials: T
authors.lastname: Gong
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Zhang
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Yunming
authors.initials: Y
authors.lastname: Li
authors.forename: Yulong
authors.initials: Y
authors.lastname: Shang
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.forename: Gui
authors.initials: G
authors.lastname: Ren
authors.forename: Bin
authors.initials: B
authors.lastname: Feng
authors.forename: Juntang
authors.initials: J
authors.lastname: Li
authors.forename: Qifei
authors.initials: Q
authors.lastname: Tian
authors.forename: Shanhong
authors.initials: S
authors.lastname: Tang
authors.forename: Li
authors.initials: L
authors.lastname: Sun
authors.forename: Mengbin
authors.initials: M
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Zhang
authors.forename: Daiming
authors.initials: D
authors.lastname: Fan
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051361:Cyclin-Dependent Kinase 6 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C545567:MIRN137 microRNA, human; D035683:MicroRNAs; C495911:CDK6 protein, human; D051361:Cyclin-Dependent Kinase 6