Lu Jun, Zhang Qianqian, Mo Licai, Chen Weiying, Mao Linghong
Department of Urology, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Taizhou, Zhejiang 310000, P.R. China.
Department of Urology, Enze Hospital, Taizhou Enze Medical Center, Taizhou, Zhejiang 310000, P.R. China.
Oncol Lett. 2023 Jul 27;26(3):395. doi: 10.3892/ol.2023.13981. eCollection 2023 Sep.
Clear cell renal cell carcinoma (ccRCC) is the most prominent subtype of renal cancer and E47-like factors (ELFs) are important in tumorigenesis; however, the specific role of key ELFs in ccRCC remains unclear. The present study comprehensively analyzed RNA sequencing and clinical data from multiple databases, and identified differentially expressed ELFs (ELF3-5) in ccRCC. The DNA promoter methylation, genetic variation and clinical significance of ELF3-5 in ccRCC were analyzed using the cBioPortal and UALCAN databases. The association between ELF3-5 and multiple immune cell infiltration was analyzed using Tumor Immune Estimation Resource. Subsequently, ELF4 was selected and its association with biological functions was assessed. Cell counting kit-8 (CCK-8), colony formation, Transwell, macrophage chemotaxis and polarization assays were conducted to validate the functions of ELF4. Notably, the mRNA expression levels of ELF4 were significantly upregulated in ccRCC, whereas ELF3 and ELF5 mRNA expression levels were significantly downregulated. Clinical significance analysis revealed that ELF4 showed a high clinical significance with tumor grade, clear cell type A and B subtypes, and incidence rates of amplification in genetic variation. Further analyses indicated that ELF4 may be involved in multiple immune cell differentiation. Additionally, cell experiments revealed that ELF4 inhibition downregulated 769-P and 786-O proliferation, migration and invasion. Knockdown of ELF4 in cancer cells also inhibited M2 macrophage polarization and chemotaxis towards 769-P and 786-O cells. Conclusively, the present findings indicated the clinical significance of ELF4 in ccRCC, and verified its key role in driving cell proliferation, migration and invasion, and promoting M2 macrophage polarization and chemotaxis in ccRCC.
透明细胞肾细胞癌（ccRCC）是肾癌最主要的亚型，E47样因子（ELFs）在肿瘤发生中起重要作用；然而，关键ELFs在ccRCC中的具体作用仍不清楚。本研究综合分析了多个数据库的RNA测序和临床数据，鉴定出ccRCC中差异表达的ELFs（ELF3 - 5）。使用cBioPortal和UALCAN数据库分析了ELF3 - 5在ccRCC中的DNA启动子甲基化、基因变异及临床意义。使用肿瘤免疫估计资源分析了ELF3 - 5与多种免疫细胞浸润之间的关联。随后，选择ELF4并评估其与生物学功能的关联。进行细胞计数试剂盒 - 8（CCK - 8）、集落形成、Transwell、巨噬细胞趋化性和极化分析以验证ELF4的功能。值得注意的是，ELF4的mRNA表达水平在ccRCC中显著上调，而ELF3和ELF5的mRNA表达水平显著下调。临床意义分析显示，ELF4在肿瘤分级、透明细胞A和B亚型以及基因变异中的扩增发生率方面具有较高的临床意义。进一步分析表明，ELF4可能参与多种免疫细胞分化。此外，细胞实验表明，抑制ELF4可下调769 - P和786 - O细胞的增殖、迁移和侵袭。在癌细胞中敲低ELF4也抑制了M2巨噬细胞极化以及对769 - P和786 - O细胞的趋化性。总之，本研究结果表明ELF4在ccRCC中的临床意义，并验证了其在驱动ccRCC细胞增殖、迁移和侵袭以及促进M2巨噬细胞极化和趋化性中的关键作用。
