title: MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer.
abstract: OBJECTIVE
  MicroRNAs (miRNA) have been documented playing a critical role in cancer development and progression. In this study, we investigate the role of miR-148a in gastric cancer metastasis.
  
  
  METHODS
  We examined miR-148a levels in 90 gastric cancer samples by qRT-PCR and analyzed the clinicopathologic significance of miR-148a expression. The gastric cancer cells stably expressing miRNA-148a were analyzed for migration and invasion assays in vitro and metastasis assays in vivo; the target genes of miR-148a were further explored.
  
  
  RESULTS
  We found that miR-148a expression was suppressed by more than 4-fold in gastric cancer compared with their corresponding nontumorous tissues, and the downregulated miR-148a was significantly associated with tumor-node-metastasis (TNM) stage and lymph node-metastasis. Functional assays showed that overexpression of miR-148a suppressed gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, overexpression of miR-148a in GC cells could reduce the mRNA and protein levels of ROCK1, whereas miR-148a silencing significantly increased ROCK1 expression. Luciferase assays confirmed that miR-148a could directly bind to the 2 sites of 3' untranslated region of ROCK1. Moreover, in gastric cancer tissues, we observed an inverse correlation between miR-148a and ROCK1 expression. Knockdown of ROCK1 significantly inhibited gastric cancer cell migration and invasion resembling that of miR-148a overexpression. We further found that ROCK1 was involved in miR-148a-induced suppression of gastric cancer cell migration and invasion.
  
  
  CONCLUSIONS
  miR-148a functions as a tumor metastasis suppressor in gastric cancer, and downregulation of miR-148a contributes to gastric cancer lymph node-metastasis and progression. miR-148a may have a therapeutic potential to suppress gastric cancer metastasis.
authors: Department of Gastric Cancer and Soft Tissue Sarcomas, Fudan University Shanghai Cancer Center and Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
authors: Biqiang
authors: B
authors: Zheng
authors: Linhui
authors: L
authors: Liang
authors: Chunmeng
authors: C
authors: Wang
authors: Shenglin
authors: S
authors: Huang
authors: Xi
authors: X
authors: Cao
authors: Ruopeng
authors: R
authors: Zha
authors: Li
authors: L
authors: Liu
authors: Deshui
authors: D
authors: Jia
authors: Qi
authors: Q
authors: Tian
authors: Jianghong
authors: J
authors: Wu
authors: Yanwei
authors: Y
authors: Ye
authors: Qifeng
authors: Q
authors: Wang
authors: Ziwen
authors: Z
authors: Long
authors: Ye
authors: Y
authors: Zhou
authors: Chunyan
authors: C
authors: Du
authors: Xianghuo
authors: X
authors: He
authors: Yingqiang
authors: Y
authors: Shi
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D009374:Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014183:Transplantation, Heterologous; D054460:rho-Associated Kinases / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; C515851:ROCK1 protein, human; D054460:rho-Associated Kinases