title: MicroRNA-130b promotes proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling.
abstract: Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths owing to its high rate of postoperative recurrence and metastasis. New research is continuously identifying novel metastasis-associated oncogenes and tumor suppressor genes. miRNAs are noncoding RNAs that regulate protein synthesis post-translationally. miR-130b is one of several miRNAs involved in tumor metastasis. However, the role of miR-130b in HCC remains controversial. Here, we demonstrate that miR-130b is highly expressed in HCC and that it correlates with tumor number, vascular invasion, and TNM stage-important predictors of postoperative recurrence and metastases. Moreover, high levels of miR-130b predicted poor overall and disease-free survival of HCC patients, and in vitro and in vivo research revealed that knockdown or overexpression of miR-130b inhibited and promoted proliferation and metastasis of HCC cells, respectively. We identified PTEN as a direct functional target of miR-130b using miRNA databases and a dual luciferase report assay. Next, using a gain and loss assay and epithelial-mesenchymal transition (EMT) relative assays, we show that miR-130b may promote proliferation and EMT-induced metastasis via PTEN/p-AKT/HIF-1α signaling. Collectively, our data suggests that miR-130b may have prognostic value in HCC. Additionally, the miR-130b/PTEN/p-AKT/HIF-1α axis identified in this study provides novel insight into the mechanisms of HCC metastasis, which may facilitate the development of new therapeutics against HCC.
authors: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Rui-Min
authors: RM
authors: Chang
authors: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Jiang-Feng
authors: JF
authors: Xu
authors: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Feng
authors: F
authors: Fang
authors: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors: Hao
authors: H
authors: Yang
authors: Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, China. lianyueyang@hotmail.com.|Liver Cancer Laboratory, Department of Surgery, Xiangya Hospital, Xiangya Road 87, Changsha, 410008, Hunan, China. lianyueyang@hotmail.com.
authors: Lian-Yue
authors: LY
authors: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000401:mortality / Q000473:pathology* / Q000556:secondary; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000502:physiology*; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000502:physiology*; D051059:PTEN Phosphohydrolase / Q000502:physiology*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D012334:RNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics*; D015398:Signal Transduction
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: EMT; PTEN; Prognosis; Solitary large hepatocellular carcinoma; miR-130b