title: MicroRNA-145 and MicroRNA-133a Inhibited Proliferation, Migration, and Invasion, While Promoted Apoptosis in Hepatocellular Carcinoma Cells Via Targeting FSCN1.
abstract: BACKGROUND
  Deregulation of FSCN1 has been observed in human cancers. However, the regulatory mechanism of FSCN1 in hepatocellular carcinoma (HCC) remains largely unknown.
  
  
  OBJECTIVE
  Our study aimed to reveal the roles of microRNA (miR)-133a, miR-145, and FSCN1 in HCC cells.
  
  
  METHODS
  Real-time RT-PCR and western blot were performed to determine the expression of miR-133a, miR-145, and FSCN1. Luciferase reporter assay was used to determine whether FSCN1 was a target of miR-133a and miR-145. Effects of miR-133a, miR-145, and FSCN1 on HCC cell proliferation, apoptosis, migration, and invasion were then investigated.
  
  
  RESULTS
  We showed that the expression of FSCN1 was increased in HCC tissues compared to the normal adjacent tissues. Moreover, upregulation of FSCN1 and downregulation of miR-145 and miR-133a co-existed in HCC. Functional studies revealed that miR-145 and miR-133a negatively regulated the expression of FSCN1 in HCC cells, via directly binding to the 3'-untranslational region of FSCN1 mRNA. Overexpression of miR-145 and miR-133a led to decreased FSCN1 expression, and downregulation of miR-145 and miR-133a resulted in increased FSCN1 expression in HCC cells. Furthermore, overexpression of miR-145 and miR-133a inhibited cellular proliferation, migration, and invasion, while promoted apoptosis in HCC cells. On the contrary, inhibition of miR-145 and miR-133a promoted cellular proliferation, migration, and invasion, while suppressed apoptosis in HCC cells.
  
  
  CONCLUSIONS
  Our study suggests that the abnormal upregulation of FSCN1 in HCC is associated with downregulation of miR-145 and miR-133a, and miR-145 and miR-133a inhibit malignant progression of HCC in vitro, possibly via directly targeting FSCN1.
authors.affiliation: Centre of Experimental Medicine, Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
authors.forename: Guohui
authors.initials: G
authors.lastname: Wang
authors.affiliation: Centre of Experimental Medicine, Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, China.
authors.forename: Shaihong
authors.initials: S
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, Hunan, China.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Department of Pathology, Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, Hunan, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Pathology, Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, Hunan, China.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Pathology, Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Changsha, 410013, Hunan, China. xiangyafuhua@163.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Fu
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics*; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000473:pathology; D035683:MicroRNAs / Q000378:metabolism*; D008840:Microfilament Proteins / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014407:Tumor Cells, Cultured
chemical_list: D002352:Carrier Proteins; C502658:FSCN1 protein, human; C548234:MIRN133 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D008840:Microfilament Proteins
keywords: FSCN1; Hepatocellular carcinoma; MicroRNA-133a; MicroRNA-145