title: miR-338-3p suppresses invasion of liver cancer cell by targeting smoothened.
abstract: MicroRNAs are involved in human carcinogenesis and cancer progression. Our previous study has shown that loss of miR-338-3p expression is associated with clinical aggressiveness of hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of miR-338-3p remain unknown in HCC. To determine whether and how miR-338-3p influences liver cancer cell invasion, we studied miR-338-3p in the liver cancer cell lines, and we found that miR-338-3p is down-regulated in treated cells. Forced expression of miR-338-3p in SK-HEP-1 cells suppressed cell migration and invasion, whereas inhibition of miR-338-3p in SMMC-7721 cells induced cell migration and invasion. Furthermore, smoothened (SMO) was identified as a direct target of miR-338-3p. Forced expression of miR-338-3p down-regulated SMO and matrix metalloproteinase (MMP)-9 expression, but inhibition of miR-338-3p up-regulated SMO and MMP9 expression. However, small interfering RNA targeted SMO reversed the effects induced by blockade of miR-338-3p. SMO and MMP9 were overexpressed and associated with invasion and metastasis in HCC tissues. These data indicate that miR-338-3p suppresses cell invasion by targeting the smoothened gene in liver cancer in vitro and miR-338-3p might be a novel potential strategy for liver cancer treatment.
authors.affiliation: Surgical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510080, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Huang
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Wen
authors.forename: Lian-Zhou
authors.initials: LZ
authors.lastname: Chen
authors.forename: Jiong
authors.initials: J
authors.lastname: Bi
authors.forename: Long-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Su
authors.forename: Wen-Tao
authors.initials: WT
authors.lastname: Zeng
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D018390:Gene Targeting; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D000072086:Smoothened Receptor; D014407:Tumor Cells, Cultured
chemical_list: C532050:MIRN338 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D043562:Receptors, G-Protein-Coupled; C491023:SMO protein, human; D000072086:Smoothened Receptor; D020780:Matrix Metalloproteinase 9