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

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
• e3IFa
• PI3K/AKT
• tumor growth
• malignant behaviors

Abbreviations

CRC	=	colorectal cancer
eIF3a	=	eukaryotic initiation factor 3a
IHC	=	Immunohistochemistry
KEGG	=	Kyoto Encyclopedia of Genes and Genomes
DAB	=	3,3-diaminobenzidine
PPI	=	protein-protein interaction

Acknowledgments

We appreciate the GEO, ONCOMINE, CCLE, GO, and KEGG databases for providing open access. We would like to thank Editage (www.editage.cn) for English language editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Conceptualization, C.H., D.W. and Y.L.; methodology, C.H., D.W., Y.Z.; software, T.Z., H.B.; validation, T.W., Y.Z., X.L.; formal analysis, J.R., Y.L.; investigation, J.R.; resources, Y.L.; data curation, C.H., Y.L. and X.L.; writing original draft preparation, C.H., D.W.; writing review and editing, Y.L.; visualization, C.H., X.L.; supervision, Y.L.; project administration, Y.L.; funding acquisition, Y.L. All authors have read and agreed to the published version of the manuscript.

Data availability statement

The data used to support the findings of this study are available from the corresponding author upon request.

Institutional review board statement

The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Animal Experimental Ethics Committee of GDMU (protocol code GDY202090 and date of approval 2020. 03. 13).

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/15384047.2024.2355703

Additional information

Funding

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