TRIM7 suppresses cell invasion and migration through inhibiting HIF‐1 alpha accumulation in clear cell renal cell carcinoma

Clear cell renal cell carcinoma (ccRCC) is one frequent form of urologic malignancy characterized by deregulated hypoxia-inducible factor signaling, genetic and epigenetic alterations. Metastasis is the leading cause of mortality from ccRCC, and understanding the underlying mechanism of this event will provide better strategies for its management. Here, we identify tripartite motif containing 7 (TRIM7) as a tumor suppressor in ccRCC cells, which negatively regulates HIF-1 alpha signaling through targeting the proto‑oncogene Src. We observed the downregulated expression of TRIM7 in clinical ccRCC tissues and its correlation with the poor prognosis. In Caki-1 cells, depletion of TRIM7 increased cell migration and invasion under normoxic and hypoxic conditions. TRIM7 markedly reduced the abundance of Src protein via the ubiquitin-proteasome pathway. Further study showed that TRIM7 affected HIF-1α accumulation though targeting either the Src-triggered PI3K/AKT/mTOR signaling pathway or ROS production. Overall, our findings highlight a novel mechanism for negative regulation of HIF-1 signaling pathway by TRIM7 and define a promising therapeutic strategy for ccRCC by modulating TRIM7.

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