title: MicroRNA-140-5p suppresses tumor growth and metastasis by targeting transforming growth factor β receptor 1 and fibroblast growth factor 9 in hepatocellular carcinoma.
abstract: By comparing the expression profiles of microRNAs (miRNAs) in different hepatocellular carcinoma (HCC) subtypes, we identified miR-140-5p as an HCC-related miRNA. We found that miR-140-5p was significantly decreased in HCC tissues and all of six liver cancer cell lines examined and its expression levels were correlated with multiple nodules, vein invasion, capsular formation, and differentiation, as well as overall and disease-free survival of HCC. We also found that miR-140-5p suppressed HCC cell proliferation and HCC metastasis. Multipathway reporter arrays suggested that miR-140-5p inhibited transforming growth factor β (TGF-β) and mitogen-activated protein kinase / extracellular signal-regulated kinase (MAPK/ERK) signaling. TGFB receptor 1 (TGFBR1) and fibroblast growth factor 9 (FGF9) were then characterized as the direct targets for miR-140-5p after it was found that ectopic miR-140-5p expression suppressed TGFBR1 and FGF9 expression. Silencing TGFBR1 and FGF9 by small interfering RNA (siRNA) resembled the phenotype resulting from ectopic miR-140-5p expression, while overexpression of TGFBR1 and FGF9 attenuated the effect of miR-140-5p on HCC growth and metastasis.
  
  
  CONCLUSIONS
  These data elucidated a tumor suppressor role for miR-140-5p in HCC development and progression with therapeutic potential. Our correlation studies in clinical HCC samples further suggest that miR-140-5p could be a valuable biomarker for HCC prognosis.
authors: Liver Cancer Laboratory, Xiangya Hospital, Central South University, Hunan, China.
authors: Hao
authors: H
authors: Yang
authors: Feng
authors: F
authors: Fang
authors: Ruimin
authors: R
authors: Chang
authors: Lianyue
authors: L
authors: Yang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D015536:Down-Regulation; D005260:Female; D051525:Fibroblast Growth Factor 9 / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009362:Neoplasm Metastasis / Q000517:prevention & control; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects*
chemical_list: D014408:Biomarkers, Tumor; C496459:FGF9 protein, human; D051525:Fibroblast Growth Factor 9; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse