MicroRNA-23b functions as an oncogene and activates AKT/GSK3β/β-catenin signaling by targeting ST7L in hepatocellular carcinoma

Cell Death Dis. 2017 May 18;8(5):e2804. doi: 10.1038/cddis.2017.216.

Abstract

Hepatocellular carcinoma (HCC) is a malignant tumor and threatens human life worldwide, whereas the etiology and pathogenesis of HCC have not been fully determined. In the past few years, many microRNAs (miRNAs) have been proved to have important roles in tumorigenesis of HCC. In this study, we found that miR-23b was significantly upregulated in tumor tissues of HCC patients. Functional tests showed that miR-23b could promote HCC cell proliferation and metastasis in vitro and in vivo. Then, mechanistic investigations suggested that ST7L was a direct target of miR-23b and involved in the promotion effects of miR-23b on HCC tumorigenesis and metastasis. Furthermore, our study indicated that ST7L could interact with the carboxyl terminal region of AKT and suppress AKT/GSK3β/β-catenin pathway in HCC cells. In conclusion, our study revealed important roles of miR-23b and ST7L in progression of HCC.

MeSH terms

  • Aged
  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Enzyme Activation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Neoplasm Metastasis
  • Oncogenes*
  • Protein Binding
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction*
  • Tumor Stem Cell Assay
  • Tumor Suppressor Proteins
  • Up-Regulation / genetics
  • beta Catenin / metabolism

Substances

  • MIRN23a microRNA, human
  • MicroRNAs
  • RNA-Binding Proteins
  • ST7L protein, human
  • Tumor Suppressor Proteins
  • beta Catenin
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt