eIf3a mediates malignant biological behaviors in colorectal cancer through the PI3K/AKT signaling pathway

Cancer Biol Ther. 2024 Dec 31;25(1):2355703. doi: 10.1080/15384047.2024.2355703. Epub 2024 May 23.

Abstract

Colorectal cancer (CRC) is among the most common gastrointestinal malignancies worldwide. eIF3a is highly expressed in a variety of cancer types, yet its role in CRC remains unclear. We introduced ectopic eIF3a expression in CRC cells to investigate its relevance to various malignant behaviors. Further, we silenced eIF3a to explore its effect on tumor growth in a nude mouse tumor xenograft model. Finally, the molecular mechanisms through which eIF3a regulates malignancy in CRC cells were explored through bioinformatics analysis combined with the use of a specific PI3K inhibitor (LY294002). eIF3a was highly expressed in the peripheral blood and cancer tissue of CRC patients. Malignancy and tumor growth were significantly inhibited by silencing eIF3a, while overexpression promoted malignant behaviors, with a positive correlation between PI3K/AKT activation and eIF3a expression. Taken together, eIF3a plays an oncogenic role in CRC by regulating PI3K/AKT signaling and is a potential biomarker for CRC diagnosis and prognostic monitoring.

Keywords: Colorectal cancer; PI3K/AKT; e3IFa; malignant behaviors; tumor growth.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation
  • Colorectal Neoplasms* / genetics
  • Colorectal Neoplasms* / metabolism
  • Colorectal Neoplasms* / pathology
  • Eukaryotic Initiation Factor-3* / genetics
  • Eukaryotic Initiation Factor-3* / metabolism
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases* / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism
  • Signal Transduction*
  • Xenograft Model Antitumor Assays

Substances

  • Eukaryotic Initiation Factor-3
  • Proto-Oncogene Proteins c-akt
  • Phosphatidylinositol 3-Kinases
  • EIF3A protein, human

Grants and funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.