title: MicroRNA-148b is frequently down-regulated in gastric cancer and acts as a tumor suppressor by inhibiting cell proliferation.
abstract: BACKGROUND
  MicroRNAs (miRNAs) are involved in cancer development and progression, acting as tumor suppressors or oncogenes. Our previous studies have revealed that miR-148a and miR-152 are significantly down-regulated in gastrointestinal cancers. Interestingly, miR-148b has the same "seed sequences" as miR-148a and miR-152. Although aberrant expression of miR-148b has been observed in several types of cancer, its pathophysiologic role and relevance to tumorigenesis are still largely unknown. The purpose of this study was to elucidate the molecular mechanisms by which miR-148b acts as a tumor suppressor in gastric cancer.
  
  
  RESULTS
  We showed significant down-regulation of miR-148b in 106 gastric cancer tissues and four gastric cancer cell lines, compared with their non-tumor counterparts by real-time RT-PCR. In situ hybridization of ten cases confirmed an overt decrease in the level of miR-148b in gastric cancer tissues. Moreover, the expression of miR-148b was demonstrated to be associated with tumor size (P = 0.027) by a Mann-Whitney U test. We also found that miR-148b could inhibit cell proliferation in vitro by MTT assay, growth curves and an anchorage-independent growth assay in MGC-803, SGC-7901, BGC-823 and AGS cells. An experiment in nude mice revealed that miR-148b could suppress tumorigenicity in vivo. Using a luciferase activity assay and western blot, CCKBR was identified as a target of miR-148b in cells. Moreover, an obvious inverse correlation was observed between the expression of CCKBR protein and miR-148b in 49 pairs of tissues (P = 0.002, Spearman's correlation).
  
  
  CONCLUSIONS
  These findings provide important evidence that miR-148b targets CCKBR and is significant in suppressing gastric cancer cell growth. Maybe miR-148b would become a potential biomarker and therapeutic target against gastric cancer.
authors.affiliation: Department of Surgical Oncology and General Surgery, First Hospital of China Medical University, 155 North Nanjing Street, Heping District, Shenyang City 110001, China.
authors.forename: Yong-Xi
authors.initials: YX
authors.lastname: Song
authors.forename: Zhen-Yu
authors.initials: ZY
authors.lastname: Yue
authors.forename: Zhen-Ning
authors.initials: ZN
authors.lastname: Wang
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Luo
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
authors.forename: Xue
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.forename: Cheng-Zhong
authors.initials: CZ
authors.lastname: Xing
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D005260:Female; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009368:Neoplasm Transplantation; D043887:Receptor, Cholecystokinin B / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D043887:Receptor, Cholecystokinin B