title: miR-99b promotes metastasis of hepatocellular carcinoma through inhibition of claudin 11 expression and may serve as a prognostic marker.
abstract: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death worldwide, mainly due to its high rates of postoperative recurrence and metastasis. Moreover, there is no widely accepted prognostic marker of recurrence. Therefore, the aim of the present study was to determine whether such a marker could be provided by a microRNA (miRNA), since recent evidence indicates that miRNAs are important contributors to the metastatic phenotype. In the present study, we showed that miR-99b was expressed at high levels in tissues of patients with HCC and in cell lines derived from HCCs. Elevated levels of miR-99b predicted poor overall survival as well as disease-free survival of patients with HCC. Moreover, miR-99b expression levels correlated with capsule formation and microvascular invasion, which are required for postoperative recurrence. Overexpression or knockdown of miR-99b expression increased or inhibited, respectively, the metastasis of HCC cells in vitro. Furthermore, using a dual‑luciferase assay, we demonstrated that miR-99b inhibited the expression of claudin 11 (CLDN11), a component of tight junction strands by directly targeting the 3'-untranslated region of CLDN11 mRNA. In addition, CLDN11 expression was increased or decreased when miR-99b expression was inhibited or elevated in the HCC cells, respectively. Moreover, the expression of miR-99b was inversely correlated with CLDN11 mRNA or CLDN11 levels in the HCC tissues. These findings suggest that a high level of miR-99b expression is an independent prognostic factor and correlates with poor survival of patients with HCC. Therefore, inhibition of miR-99b expression may serve as a therapeutic approach for inhibiting the metastatic phenotype of HCC.
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiwu
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Department of General Surgery, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Wang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D057167:Claudins / Q000037:antagonists & inhibitors / Q000235:genetics*; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*
chemical_list: C120453:CLDN11 protein, human; D057167:Claudins; C561679:MIRN99 microRNA, human; D035683:MicroRNAs