HSF4 promotes renal cell carcinoma progression and is associated with PI3K/Akt pathway

BACKGROUND: Renal cell carcinoma (RCC) is a common urological malignancy, accounting for approximately 2% of global cancer-related mortality. Heat shock factors (HSFs) are transcription factors that regulate cell stress reaction. However, the exact mode of action of HSF4 in cancer, particularly RCC, is still unknown. OBJECTIVE: To investigate the expression pattern of HSF4 in RCC and its potential molecular mechanism (especially the association with the PI3K/Akt pathway), so as to identify a new therapeutic target for RCC. METHODS: Bioinformatics analyses were performed to assess HSF4 expression and its prognosis relevance in RCC. The effects of HSF4 on RCC were studied with both in vitro and in vivo experiments. The transcriptome sequencing results were analyzed for both the gene knockdown and control RCC cells to predict relevant RCC signaling pathways. RESULTS: Our experimental results indicate that HSF4 knockdown can prevent the occurrence and spread of RCC in the body, as well as the growth and invasion of RCC cells. Mechanistically, HSF4 knockdown led to a significant decrease in the protein levels of PI3K, p-AKT, β-catenin, and c-Myc. These findings demonstrate that HSF4 promotes RCC progression by concurrently activating the PI3K/AKT and Wnt/β-catenin signaling pathways. CONCLUSION: Our findings identify that HSF4 is highly expressed in RCC and can promote the occurrence and development of RCC. Therefore, HSF4 may be a potential therapeutic target for RCC.