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ELOVL5 promotes cell proliferation and invasion in renal cell carcinoma

ABSTRACT: Fatty acid is a main component of lipid. The differences of chain-length and pattern of saturation / desaturation in fatty acid are essential for diversity of biological lipid functions. Elongation of very-long-chain fatty acids (ELOVL) plays a critical role in regulating the elongation of fatty acid and ELOVL 1 to 7 are reported in the present. In several cancers but renal cell carcinoma (RCC), the relationship between ELOVLs and cancer progression has been reported. In TCGA cohort, ELOVL5 expression is associated with advanced TNM stage and poor prognosis. We performed CRISPR-Cas9 targeted knockout of ELOVL5 in 2 different RCC cell lines, ACHN and 786-O, respectively. ELOVL5 knockout significantly suppressed cellular invasion, migration and proliferation in vitro and in vivo. In ingenuity Pathway Analysis, Akt signaling activation was decreased in ELOVL5-KO cells. In western blotting analysis, the phosphorylation level of Akt was inhibited in ELOVL5-KO cells. Resultantly, it was suggested that ELOVL5 is involved in the phosphorylation level of Akt and affects cancer progression in RCC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE192403 | GEO | 2022/08/17

REPOSITORIES: GEO

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Project description:Recent advancement in cancer research has shown that tumours are highly heterogeneous and multiple phenotypically different cell populations are found in single nodule. Cancer development and tumour growth is driven by specific type of cells - cancer stem cells or tumour initiating cells (CSCs/TICs), which are to be responsible for tumour growth, metastatic spread and drug resistance. This research was designed to verify the presence of tumour initiating cells in renal cancer cell lines. Subsequently, we aimed to characterize phenotype and cell biology of CD105+ cells, defined previously as renal cell carcinoma tumour initiating cells. Main goal of the project was to describe gene expression profile of tumour initiating cells originating from primary tumour and of metastatic origin. Metastatic RCC cell lines (ACHN and Caki-1) demonstrated higher colony forming ability comparing to primary RCC cell lines. We investigated presence of CD105+ cells in RCC cell lines. Furthermore, metastatic RCC cell lines have higher CD105+ cell population and higher expression for stemness genes (Oct-4 and Nanog). CD105+ cells adopt 3D grapes like structure under handing drop condition. Sorted CD105+ cells were found positive for human MSC makers such as CD90, CD73, CD44, CD146 and alkaline phosphatase activity. In addition, CD105+ cells were unable to expressed maker for CD24, CD34, CD11b, CD19, CD45 and HLA-DR. 1411 genes were commonly differentially expressed in CD105+ cells (both from primary (Caki-2) and metastatic RCC (ACHN)) cells in comparison to healthy kidney epithelial cell line (ASE-5063). TGF-β, Wnt/β-catenine, Epithelial-Mesenchymal Transition (EMT), Rap1 signaling, PI3K-Akt signaling and Hippo signaling pathway were altered in CD105+ cells after IPA and KEGG pathway analysis. TGFB1, ERBB2, and TNF are most significant transcriptional regulators activated in these cells. Altogether, our results indicate that RCC-CD105+ cells may represents a novel target for CSCs/TICs phenotype and their gene expression profile could be used as initial data for new functional studies and drug design.

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ELOVL5 promotes cell proliferation and invasion in renal cell carcinoma

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