Clear cell renal cell carcinoma (ccRCC) is the most common primary kidney cancer in adults, and the identification of biomarkers involved in the pathogenesis and prognosis of ccRCC is crucial for early diagnosis and anticancer treatment. In this study, we demonstrate that thioredoxin domain-containing protein 5 (TXNDC5) expression is markedly upregulated in ccRCC tissues in comparison with adjacent non-cancerous tissues through quantitative RT-PCR, Western blotting, and immunohistochemical analyses. Importantly, TXNDC5 expression is negatively correlated with the overall survival of patients. Knockdown of TXNDC5 by siRNAs inhibits the cell growth, migration, and invasion of ccRCC cells as well as sensitizes ccRCC cells to chemotherapeutic drugs, such as Camptothecin and 5-Fluorouracil. Moreover, we used complementary DNA (cDNA) microarray analyses to explore the underlying molecular mechanisms of TXNDC5 in the pathogenesis of ccRCC. We demonstrate that knockdown of TXNDC5 affects the messenger RNA (mRNA) and protein levels of numerous important genes associated with tumorigenesis. In summary, our findings indicate that TXNDC5 performs an essential function in ccRCC pathogenesis and can serve as a novel prognostic marker of ccRCC.
Keywords: Apoptosis; ER stress; Renal cell carcinoma; TXNDC5.