title: MicroRNA-455 regulates migration and invasion of human hepatocellular carcinoma by targeting Runx2.
abstract: MicroRNA-455 (miR-455) has been considered as a novel cancer-related miRNA and dysregulated expression frequently occurs in various human types of cancer. However, its clinical significance, its biological function and the underlying molecular signaling involved in hepatocellular carcinoma (HCC) remain to be elucidated. In the present study, we found that the expression level of miR-455 was significantly downregulated in both HCC tissues and cell lines. Low expression of miR-455 was significantly associated with poor prognostic features including multiple tumor nodes, high Edmondson‑Steiner grading, advanced tumor-node‑metastasis (TNM) stage and venous infiltration. In addition, our data revealed that miR-455 was a novel prognostic indicator for predicting the 5-year overall and disease-free survival of HCC patients. The gain- and loss-of-function studies revealed that miR-455 significantly suppressed migration and invasion of HCC cells in vitro. miR-455 was inversely correlated with runt-related transcription factor 2 (Runx2) expression in HCC samples. Moreover, we identified that miR-455 inversely regulated Runx2 expression in HCC cells. In this investigation, Runx2 was found to be a direct downstream target of miR-455. Evidently, alteration in Runx2 expression suppressed the effect of miR-455 on HCC cell migration and invasion. In conclusion, our data demonstrated that miR-455 promotes HCC growth by targeting Runx2 and can potentially be regarded as a novel prognostic indicator and valuable therapeutic strategy for HCC.
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Le
authors.initials: L
authors.lastname: Qin
authors.affiliation: Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pediatric Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.affiliation: Medical Function Center of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Yangping
authors.initials: Y
authors.lastname: Shentu
authors.affiliation: Department of Medical Imaging, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Xie
mesh_terms: D000368:Aged; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics* / Q000378:metabolism; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000502:physiology*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016016:Proportional Hazards Models; D034622:RNA Interference
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; C583404:MIRN455 microRNA, human; D035683:MicroRNAs; C493709:RUNX2 protein, human