UHRF1 is regulated by miR-124-3p and promotes cell proliferation in intrahepatic cholangiocarcinoma

J Cell Physiol. 2019 Nov;234(11):19875-19885. doi: 10.1002/jcp.28586. Epub 2019 Apr 15.

Abstract

Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is abnormally overexpressed in multiple cancers and closely correlated with tumor-promoting effects, such as high proliferation. However, how UHRF1 functions in intrahepatic cholangiocarcinoma (ICC) has not yet been determined. Herein, we found that UHRF1 is overexpressed in ICC tissues. Downregulated UHRF1 attenuated the transition of the G1/S cell cycle and then suppressed cell proliferation in vitro and tumor growth in vivo. Moreover, upstream regulators of the UHRF1 expression were predicted, and we found that direct binding of miR-124-3p inhibited the UHRF1 expression. Elevated miR-124-3p suppressed proliferation and led to the arrest of the cell cycle. Furthermore, the expression of UHRF1 was positively correlated with PCNA. Clinically, we showed that elevated UHRF1 was associated with poor prognosis, and served as an independent prognostic factor in ICC patients. Together, these findings demonstrate that UHRF1, regulated by miR-124-3p, acts as a tumor promoter by promoting cell proliferation in ICC.

Keywords: ICC; UHRF1; cell cycle; miR-124-3p; prognosis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • CCAAT-Enhancer-Binding Proteins / genetics*
  • CCAAT-Enhancer-Binding Proteins / metabolism
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cholangiocarcinoma / genetics*
  • Cholangiocarcinoma / pathology*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Proliferating Cell Nuclear Antigen / metabolism
  • Ubiquitin-Protein Ligases / genetics*
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • CCAAT-Enhancer-Binding Proteins
  • MIRN124 microRNA, human
  • MicroRNAs
  • Proliferating Cell Nuclear Antigen
  • UHRF1 protein, human
  • Ubiquitin-Protein Ligases