Retinoic acid induced 16 enhances tumorigenesis and serves as a novel tumor marker for hepatocellular carcinoma

Carcinogenesis. 2012 Dec;33(12):2578-85. doi: 10.1093/carcin/bgs289. Epub 2012 Sep 12.


Our previous work identified downregulated miR-483-5p in hepatocellular carcinoma (HCC). This study aims to identify the target of miR-483-5p, evaluate the potential value of this target as a tumor marker for HCC and explore the role of this target in HCC tumorigenesis. Upregulated retinoic acid induced 16 (RAI16) (17/18 cases) was negatively correlated with downregulated miR-483-5p (14/18 cases) in HCC tissues. The dual-luciferase reporter assay showed that RAI16 is a target of miR-483-5p. Immunohistochemistry analysis showed RAI16 was moderate or strong staining in tumor tissues but negative or weak staining in adjacent non-tumor tissues. The sensitivity and specificity of RAI16 for HCC diagnosis were 70.6 and 93.6%, respectively, and increased to 80.9 and 92.0% when combined with glypican-3. Finally, overexpression or knockdown of RAI16 increased or decreased cell viability and colony formation in HCC cell lines and enhanced or inhibited tumor cell growth in xenograft nude mice. Mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) and transforming growth factor-β pathways were mostly affected by RAI16. RAI16 could activate the phosphorylation of ERK1/2 and SMAD2/3. In conclusion, RAI16 may serve as a useful therapeutic agent for HCC gene therapy and tumor marker for HCC diagnosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers, Tumor / analysis*
  • Carcinoma, Hepatocellular / diagnosis
  • Carcinoma, Hepatocellular / etiology*
  • Carcinoma, Hepatocellular / pathology
  • Cell Transformation, Neoplastic*
  • HEK293 Cells
  • Hep G2 Cells
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / etiology*
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • MicroRNAs / antagonists & inhibitors
  • Proteins / analysis
  • Proteins / physiology*


  • Biomarkers, Tumor
  • FAM160B2 protein, human
  • MIRN483 microRNA, human
  • MicroRNAs
  • Proteins