: Clear cell renal cell carcinoma (ccRCC) is considered the second most common urogenital tract carcinoma, plaguing patients worldwide due to its high incidence and resistance to treatment. Thus, it is urgent to screen new biomarkers and decipher their molecular mechanisms to support early clinical diagnosis and targeted therapy of ccRCC. It is reported that epithelial membrane protein 3 () acts as a tumor-promoting or suppressing factor in a variety of malignant tumors, but its relationship with ccRCC remains to be explored. : The Cancer Genome Atlas (TCGA) and Oncomine database were utilized to screen the differentially expressed genes in ccRCC. Western blot and qPCR were used to verify the expression of our subject of interest, in ccRCC tissues and cell lines. Next, a series of functional experiments were conducted to explore the biological functions of in tumor cells, including cell counting kit-8, transwell, wound healing assays, Oil red O staining and triglyceride determination. Western blotting was used to explore the potential mechanism of induced ccRCC deterioration. Finally, the TIMER2.0 database was used to explore the effect of on tumor immune infiltration and its relationship with multiple immune checkpoints. : In this study, we uncovered that was more prominently expressed in ccRCC and its expression level had a significant positive correlation with the clinical stage and histopathological grade of tumor patients. Based on the TCGA database, the Receiver operating characteristic (ROC) curves showed that could be potentially utilized as a specific biomarker in diagnosing ccRCC patients. Meanwhile, six independent prognostic factors were determined and integrated into our nomogram, with an OS concordance index (C-index) of 0.760 (95% CI: 0.689-0.831). Furthermore, depletion of could alleviate the proliferation, migration, invasion, and lipid storage in ccRCC cells. Mechanistically, was shown to enhance the malignant potential of tumor cells by promoting epithelial-mesenchymal transition (EMT) and lipid accumulation. In addition, the expression of was closely related to the infiltration of a variety of immune cells, and was positively related to PD-L1, suggesting that it may be a tight connection with tumor immune escape. : Our results revealed that might be a candidate biomarker and independent prognostic indicator, and related to EMT process, lipid accumulation, as well as immune infiltration in ccRCC. Targeted therapy might be a promising and effective treatment strategy for ccRCC patients.

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http://dx.doi.org/10.52586/5018DOI Listing

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