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Abstract Background Glioma is considered the most common primary malignant tumor of the central nervous system. Although traditional treatments have not achieved satisfactory outcomes, recently, targeted therapies for glioma have shown promising efficacy. However, due to the single-target nature of targeted therapy, traditional targeted therapies are ineffective; thus, novel therapeutic targets are urgently needed. Methods The gene expression data for glioma patients were derived from the GEO (GSE4290, GSE50161), TCGA and CGGA databases. Next, the upregulated genes obtained from the above databases were cross-analyzed, finally, 10 overlapping genes (BIRC5, FOXM1, EZH2, CDK1, KIF11, KIF4A, NDC80, PBK, RRM2, and TOP2A) were ultimately screened and only KIF4A expression has the strongest correlation with clinical characteristics in glioma patients. Futher, the TCGA and CGGA database were utilized to explore the correlation of KIF4A expression with glioma prognosis. Then, qRT-PCR and Western blot was used to detect the KIF4A mRNA and protein expression level in glioma cells, respectively. And WZ-3146, the small molecule inhibitor targeting KIF4A, were screened by Cmap analysis. Subsequently, the effect of KIF4A knockdown or WZ-3146 treatment on glioma was measured by the MTT, EdU, Colony formation assay and Transwell assay. Ultimately, GSEA enrichment analysis was performed to find that the apoptotic pathway could be regulated by KIF4A in glioma, in addition, the effect of WZ-3146 on glioma apoptosis was detected by flow cytometry and Western blot. Results In the present study, we confirmed that KIF4A is abnormally overexpressed in glioma. In addition, KIF4A overexpression is a key indicator of glioma prognosis; moreover, suppressing KIF4A expression can inhibit glioma progression. We also discovered that WZ-3146, a small molecule inhibitor of KIF4A, can induce apoptosis in glioma cells and exhibit antiglioma effects. Conclusion In conclusion, these observations demonstrated that targeting KIF4A can inhibit glioma progression. With further research, WZ-3146, a small molecule inhibitor of KIF4A, could be combined with other molecular targeted drugs to cooperatively inhibit glioma progression.

Background: Glioma is considered the most common primary malignant tumor of the central nervous system. Although traditional treatments have not achieved satisfactory outcomes, recently, targeted therapies for glioma have shown promising efficacy. However, due to the single-target nature of targeted therapy, traditional targeted therapies are ineffective; thus, novel therapeutic targets are urgently needed. Methods: The gene expression data for glioma patients were derived from the GEO (GSE4290, GSE50161), TCGA and CGGA databases. Next, the upregulated genes obtained from the above databases were cross-analyzed, finally, 10 overlapping genes (BIRC5, FOXM1, EZH2, CDK1, KIF11, KIF4A, NDC80, PBK, RRM2, and TOP2A) were ultimately screened and only KIF4A expression has the strongest correlation with clinical characteristics in glioma patients. Futher, the TCGA and CGGA database were utilized to explore the correlation of KIF4A expression with glioma prognosis. Then, qRT-PCR and Western blot was used to detect the KIF4A mRNA and protein expression level in glioma cells, respectively. And WZ-3146, the small molecule inhibitor targeting KIF4A, were screened by Cmap analysis. Subsequently, the effect of KIF4A knockdown or WZ-3146 treatment on glioma was measured by the MTT, EdU, Colony formation assay and Transwell assay. Ultimately, GSEA enrichment analysis was performed to find that the apoptotic pathway could be regulated by KIF4A in glioma, in addition, the effect of WZ-3146 on glioma apoptosis was detected by flow cytometry and Western blot. Results: In the present study, we confirmed that KIF4A is abnormally overexpressed in glioma. In addition, KIF4A overexpression is a key indicator of glioma prognosis; moreover, suppressing KIF4A expression can inhibit glioma progression. We also discovered that WZ-3146, a small molecule inhibitor of KIF4A, can induce apoptosis in glioma cells and exhibit antiglioma effects. Conclusion: In conclusion, these observations demonstrated that targeting KIF4A can inhibit glioma progression. With further research, WZ-3146, a small molecule inhibitor of KIF4A, could be combined with other molecular targeted drugs to cooperatively inhibit glioma progression. [ABSTRACT FROM AUTHOR]

We studied three brothers and a maternal half-brother featuring global developmental delay, mild to moderate intellectual disability, epilepsy, microcephaly, and strabismus. All had bilateral perisylvian and perirolandic polymicrogyria, while some also had malformations of the hippocampus (malrotation and dysplasia), cerebellum (heterotopias and asymmetric aplasia), corpus callosum dysgenesis, and brainstem asymmetric dysplasia. Exome sequencing showed that all four patients had a novel variant (c.1597C>T:p.Leu533Phe) on the KIF4A gene on chromosome X. We discuss how this variant is possibly pathogenic and could explain the reported phenotype., (© 2024 The Author(s). American Journal of Medical Genetics Part A published by Wiley Periodicals LLC.)

KIF4A is upregulated in various malignancies and serves as an independent risk factor. However, its function in skin cutaneous melanoma (SKCM) and the regulation of the immunological environment remains unknown. We first explored the mRNA and protein levels of KIF4A in SKCM through public databases. Then, the co-expressed genes with KIF4A in SKCM and their functional enrichment analysis were performed. Moreover, the clinical value, relationship with immune infiltration and tumor microenvironment (TME), as well as the correlation between KIF4A and immunomodulators were evaluated. In addition, we validated the function of KIF4A by in vitro experiments such as CCK-8 assay, clone formation and wound healing assay. Our data reveal that the mRNA and protein levels of KIF4A are highly expressed in SKCM. Moreover, functional enrichment analysis of the top 50 co-expressed genes with KIF4A showed significant association with organelle fission, tubulin binding and immune processes. KIF4A can distinguish SKCM from normal tissue and predict a poorer prognosis. A negative association was observed between KIF4A and TME, and KIF4A exhibited a negative correlation with most immunomodulators. Additionally, the knockdown of KIF4A inhibited the proliferation and migration ability of A375 cells. Our findings suggest that KIF4A promotes the progression of SKCM and is negatively associated with immune infiltration and immunomodulators, which indicates a poor prognosis. [ABSTRACT FROM AUTHOR]

Background: The efficacy of chemotherapy in treating Kidney Renal Clear Cell Carcinoma (KIRC) is limited, whereas immunotherapy has shown some promising clinical outcomes. In this context, KIF4A is considered a potential therapeutic target for various cancers. Therefore, identifying the mechanism of KIF4A that can predict the prognosis and immunotherapy response of KIRC would be of significant importance., Methods: Based on the TCGA Pan-Cancer dataset, the prognostic significance of the KIF4A expression across 33 cancer types was analyzed by univariate Cox algorithm. Furthermore, overlapping differentially expressed genes (DEGs1) between the KIF4A high- and lowexpression groups and DEGs2 between the KIRC and normal groups were also analyzed. Machine learning and Cox regression algorithms were performed to obtain biomarkers and construct a prognostic model. Finally, the role of KIF4A in KIRC was analyzed using quantitative real-time PCR, transwell assay, and EdU experiment., Results: Our analysis revealed that KIF4A was significant for the prognosis of 13 cancer types. The highest correlation with KIF4A was found for KICH among the tumour mutation burden (TMB) indicators. Subsequently, a prognostic model developed with UBE2C, OTX1, PPP2R2C, and RFLNA was obtained and verified with the Renal Cell Cancer-EU/FR dataset. There was a positive correlation between risk score and immunotherapy. Furthermore, the experiment results indicated that KIF4A expression was considerably increased in the KIRC group. Besides, the proliferation, migration, and invasion abilities of KIRC tumor cells were significantly weakened after KIF4A was knocked out., Conclusion: We identified four KIF4A-related biomarkers that hold potential for prognostic assessment in KIRC. Specifically, early implementation of immunotherapy targeting these biomarkers may yield improved outcomes for patients with KIRC., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)