Downregulation of MCM8 expression restrains the malignant progression of cholangiocarcinoma

Oncol Rep. 2021 Nov;46(5):235. doi: 10.3892/or.2021.8186. Epub 2021 Sep 15.

Abstract

Cholangiocarcinoma (CCA) is a highly aggressive malignant tumor with an extremely poor prognosis. Minichromosome maintenance 8 homologous recombination repair factor (MCM8) is a helicase involved in the elongation step of DNA replication and tumorigenesis. In the present study, the clinical significance and biological function of MCM8 in CCA were investigated. The expression levels of MCM8 in CCA and paracancerous tissues were analyzed using immunohistochemical staining. The potential mechanisms underlying MCM8 and the biological effects of MCM8 in CCA cells were explored using in vitro assays and in vivo mouse xenograft models. The high expression levels of MCM8 in CCA has important clinical significance in predicting disease progression. Knockdown of MCM8 decreased proliferation, promoted apoptosis and suppressed migration of CCA cells. MCM8 knockdown also suppressed tumor growth in vivo. Mechanistically, MCM8 knockdown led to the abnormal downregulation of survivin, XIAP, HSP27, IGF‑1sR, sTNF‑R1, sTNF‑R2, TNF‑α and TNF‑β. Furthermore, downregulation of MCM8 expression inhibited the PI3K/Akt signaling pathway and induced the MAPK9 signaling pathway. MCM8 promoted the malignant progression of CCA, indicating that inhibition of MCM8 may have the potential to serve as a novel molecular targeted therapy.

Keywords: apoptosis; cholangiocarcinoma; migration; minichromosome maintenance 8 homologous recombination repair factor; proliferation.

MeSH terms

  • Animals
  • Apoptosis
  • Bile Duct Neoplasms / metabolism*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Cholangiocarcinoma / metabolism*
  • Disease Models, Animal
  • Disease Progression
  • Down-Regulation
  • Female
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Minichromosome Maintenance Proteins / metabolism*

Substances

  • MCM8 protein, human
  • Mcm8 protein, mouse
  • Minichromosome Maintenance Proteins

Grants and funding

The present study was supported by the Institutional Research Funding from The First Affiliated Hospital of Chengdu Medical College (grant no. CYFY-GQ20).