Long non-coding RNA FEZF1-AS1 promotes the proliferation and metastasis of hepatocellular carcinoma via targeting miR-107/Wnt/β-catenin axis

Aging (Albany NY). 2021 May 23;13(10):13726-13738. doi: 10.18632/aging.202960. Epub 2021 May 23.

Abstract

Hepatocellular carcinoma (HCC) is a public health problem around the world, with the molecular mechanisms being still incompletely clear. This study was carried out to explore the role and mechanism of long-noncoding RNA (lncRNA) FEZF1-AS1 in HCC progression. RNA sequencing and quantitative real time polymerase chain reaction (qRT- PCR) were applied to identify differently expressed lncRNAs in HCC tissues and adjacent normal tissues. CCK8 assay was adopted to test cell proliferation and flow cytometry was taken to detect cell apoptosis. Wound healing assay and transwell experiment were performed to determine cell migration and invasion. To validate the function of lncRNA FEZF1-AS1 in vivo, tumor-burdened models were established. The results showed that lncRNA FEZF1-AS1 level was prominently enhanced in HCC tumor specimens and overexpression of FEZF1-AS1 promoted the proliferation, migration and invasion of HCC cells. In mechanism, overexpression of FEZF1-AS1 reduced the expression of miR-107 which inhibited the activation of Wnt/β-catenin signaling. Overexpression of β-catenin promoted cell proliferation, migration and invasion which were inhibited by FEZF1-AS1 downregulation. In conclusion, our study demonstrated that FEZF1-AS1 promoted HCC progression through activating Wnt/β-catenin signaling by targeting miR-107, which provided a novel target for the therapy of HCC.

Keywords: hepatocellular carcinoma; lncRNA FEZF1-AS1; miR-107; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Down-Regulation / genetics
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Wnt Signaling Pathway* / genetics

Substances

  • MIRN107 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding