MicroRNA-92b promotes hepatocellular carcinoma progression by targeting Smad7 and is mediated by long non-coding RNA XIST

Cell Death Dis. 2016 Apr 21;7(4):e2203. doi: 10.1038/cddis.2016.100.


MicroRNA (miRNA) and long non-coding RNA (lncRNA) have been demonstrated to participate in the progression of many cancers. Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignant tumors worldwide, while the molecular mechanisms underlying HCC tumorigenesis are not completely clear. In this study, we showed that miR-92b was significantly upregulated in tumor tissue and plasma of HCC patients, and its expression level was highly correlated with gender and microvascular invasion. Functionally, miR-92b could promote cell proliferation and metastasis of HCC in vitro and in vivo. Mechanistic investigations suggested that Smad7, which exhibited an inverse relationship with miR-92b expression in HCC, was a direct target of miR-92b and could reverse its effects on HCC tumorigenesis. Furthermore, long non-coding RNA (lncRNA) X-inactive specific transcript (XIST) and miR-92b could directly interact with and repress each other, and XIST could inhibit HCC cell proliferation and metastasis by targeting miR-92b. Taken together, our study not only revealed for the first time the importance of XIST/miR-92b/Smad7 signaling axis in HCC progression but also suggested the potential value of miR-92b as a biomarker in the clinical diagnosis and treatment of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Base Sequence
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Female
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / secondary
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / blood
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • RNA, Long Noncoding / chemistry
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Sequence Alignment
  • Signal Transduction
  • Smad7 Protein / antagonists & inhibitors
  • Smad7 Protein / genetics
  • Smad7 Protein / metabolism*
  • Transplantation, Heterologous
  • Vimentin / metabolism
  • beta Catenin / metabolism


  • Biomarkers, Tumor
  • MicroRNAs
  • Oligonucleotides, Antisense
  • RNA, Long Noncoding
  • Smad7 Protein
  • Vimentin
  • XIST non-coding RNA
  • beta Catenin