NCAPD2 augments the tumorigenesis and progression of human liver cancer via the PI3K‑Akt‑mTOR signaling pathway

Int J Mol Med. 2024 Oct;54(4):84. doi: 10.3892/ijmm.2024.5408. Epub 2024 Aug 2.

Abstract

Non‑SMC condensin I complex subunit D2 (NCAPD2) is a newly identified oncogene; however, the specific biological function and molecular mechanism of NCAPD2 in liver cancer progression remain unknown. In the present study, the aberrant expression of NCAPD2 in liver cancer was investigated using public tumor databases, including TNMplot, The Cancer Genome Atlas and the International Cancer Genome Consortium based on bioinformatics analyses, and it was validated using a clinical cohort. It was revealed that NCAPD2 was significantly upregulated in liver cancer tissues compared with in control liver tissues, and NCAPD2 served as an independent prognostic factor and predicted poor prognosis in liver cancer. In addition, the expression of NCAPD2 was positively correlated with the percentage of Ki67+ cells. Finally, single‑cell sequencing data, gene‑set enrichment analyses and in vitro investigations, including cell proliferation assay, Transwell assay, wound healing assay, cell cycle experiments, cell apoptosis assay and western blotting, were carried out in human liver cancer cell lines to assess the biological mechanisms of NCAPD2 in patients with liver cancer. The results revealed that the upregulation of NCAPD2 enhanced tumor cell proliferation, invasion and cell cycle progression at the G2/M‑phase transition, and inhibited apoptosis in liver cancer cells. Furthermore, NCAPD2 overexpression was closely associated with the phosphatidylinositol 3‑kinase (PI3K)‑Akt‑mammalian target of rapamycin (mTOR)/c‑Myc signaling pathway and epithelial‑mesenchymal transition (EMT) progression in HepG2 and Huh7 cells. In addition, upregulated NCAPD2 was shown to have adverse effects on overall survival and disease‑specific survival in liver cancer. In conclusion, the overexpression of NCAPD2 was shown to lead to cell cycle progression at the G2/M‑phase transition, activation of the PI3K‑Akt‑mTOR/c‑Myc signaling pathway and EMT progression in human liver cancer cells.

Keywords: c‑Myc; epithelial‑mesenchymal transition; liver cancer; non‑SMC condensin I complex subunit D2; phosphatidylinositol 3‑kinase‑Akt‑mammalian target of rapamycin; tumor survival and progression.

MeSH terms

  • Apoptosis / genetics
  • Carcinogenesis / genetics
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation* / genetics
  • Disease Progression
  • Epithelial-Mesenchymal Transition / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / metabolism
  • Liver Neoplasms* / pathology
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction* / genetics
  • TOR Serine-Threonine Kinases* / metabolism

Substances

  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • Cell Cycle Proteins

Grants and funding

The present study was supported by the Hubei Provincial Natural Science Foundation (grant no. 2020CFB235).