miR-28-5p inhibits cholangiocarcinoma progression and predicts good prognosis of patients

Cell Cycle. 2022 Oct;21(19):2079-2090. doi: 10.1080/15384101.2022.2085359. Epub 2022 Jun 7.

Abstract

Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies. The overall five-year survival rate for cholangiocarcinoma is less than 15%. miR-28-5p has been reported to participate the development of various human cancer types. But whether miR-28-5p is associated with the clinical course of CCA patients has not been clarified. Herein, we observed that miR-28-5p was reduced in CCA tissues and predicts the poor prognosis of CCA patients. Treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-AZA) restored miR-28-5p expression in CCA cell lines. Furthermore, up-regulated miR-28-5p inhibited CCA cells growth and metastasis. Mechanistically, miR-28-5p suppressed CCA cells growth and metastasis via directly targeting CD44 molecular. Specific CD44 special siRNA abrogated the discrepancy of the proliferation and metastasis capacity between miR-28-5p-overexpression CCA cells and their control cells, which further confirmed that CD44 was required in miR-28-5p-inhibited CCA cell growth and metastasis.

Keywords: CD44; Cholangiocarcinoma; methylation; miR-28-5p; prognosis; progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bile Duct Neoplasms* / genetics
  • Bile Duct Neoplasms* / pathology
  • Bile Ducts, Intrahepatic / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cholangiocarcinoma* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism

Substances

  • MIRN28 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by the Shanghai Municipal Commission of Health and Family Planning Project [201840290]; Pudong New District Health Bureau Project [PW2019A-18]; Discipline Construction Program of Pudong New District Health Bureau [PWZbr2017-01]; Shanghai Municipal Population and Family Planning Commission [202040180].