The mechanism of long-chain acyl-CoA synthetase 3 in inhibiting cell proliferation, migration, and invasion in clear cell renal cell carcinoma.

Long-chain acyl-CoA synthases 3 (ACSL3) can activate long-chain fatty acids, which are often deregulated in tumors. However, the biological function of ACSL3 in clear cell renal cell carcinoma (ccRCC) is still unclear. In this research, the expression level, prognostic value, GO and KEGG functional enrichment analyses, genomic changes, clinical significance, immune infiltration of ACSL3 in ccRCC were comprehensively analysed. The expression levels of ACSL3 in ccRCC tissues were detected by quantitative reverse transcription-polymerase chain reaction (RT-qPCR), immunohistochemical staining (IHC), and Western blotting analysis. The proliferation, invasion, migration, apoptotic and lipid synthesis abilities of ccRCC cells were assessed using the cell counting kit (CCK-8), clone formation, scratch assay, Transwell assay, flow cytometry and Oil Red O assay, respectively. The results showed that ACSL3 was obviously downregulated in ccRCC and significantly associated with poor prognosis and clinicopathological factors of ccRCC patients. Additionally, the functional enrichment analysis indicated that ACSL3 was mainly involved in lipid synthesis and metabolism. The result of immune infiltration analysis proved that ACSL3 might regulate the tumor microenvironment of ccRCC. In addition, we demonstrated that overexpression of the ACSL3 could inhibit the proliferation, migration, and invasion of ccRCC cells, and promote apoptosis, reduce abnormal lipid accumulation. In conclusion, ACSL3 might be a novel ccRCC biomarker and the target for ccRCC tumor therapy.