KIF14 plays a role in the regulation of the cell cycle and has implications for prognosis in clear cell renal cell carcinoma.

BACKGROUND

Kinesin family member 14 (KIF14) is a significant multifunctional protein that has been linked to several malignancies. However, the varied expression profiles of KIF14 and its prognostic relevance in Clear cell renal cell carcinoma (ccRCC) have yet to be elucidated.

METHODS

Patients with ccRCC were obtained from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and ArrayExpress databases. A comparison of KIF14 expression levels between ccRCC and normal tissues was conducted using the Wilcoxon rank sum test. Logistic regression analysis was subsequently employed to evaluate the relationship between KIF14 expression and clinicopathological features. Furthermore, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) term analysis, gene set enrichment analysis (GSEA) and single sample gene set enrichment analysis (ssGSEA), as well as CIBERSORT, were utilized to elucidate the enriched pathways and functions linked to KIF14 and to quantify the level of immune cell infiltration. Kaplan-Meier analysis was conducted to assess the correlation between KIF14 expression and survival. Additionally, KIF14 expression was downregulated in A498 ccRCC cells, and their proliferation, expansion capacity, cell cycle, and apoptosis were assessed through CCK-8 assays, colony formation assays, 7-AAD staining, and Annexin V/PI staining, respectively.

RESULTS

The findings of this study demonstrate that KIF14 mRNA levels are notably increased in ccRCC. Furthermore, a positive association was observed between KIF14 expression and cancer stage, nodal metastasis, and the infiltration of various immune cells in ccRCC. High levels of KIF14 were also found to be indicative of poor survival outcomes among ccRCC patients. Knockdown of KIF14 in A498 cells resulted in reduced proliferation, diminished colony formation capacity, cell cycle arrest, increased apoptosis, and downregulation of CyclinD1 and CDK4.

CONCLUSIONS

KIF14 down-regulates cell cycle proteins CyclinD1 and CDK4 to facilitate the proliferation of ccRCC cells, suggesting its potential as a therapeutic target and prognostic biomarker in ccRCC.