1. Department of Urology, Peking University First Hospital, Beijing 100034, P.R. China
2. Hereditary Kidney Cancer Research Center, Peking University First Hospital, Beijing 100034, P.R. China
3. Institute of Urology, Peking University, Beijing 100034, P.R. China
4. National Urological Cancer Center, Beijing 100034, P.R. China
5. Department of Urology, Beijing Cancer Hospital, Beijing 100142, P.R. China
6. Beijing Institute for Cancer Research, Beijing 100142, P.R. China
Tribbles pseudokinase 3 (TRIB3) is a member of the mammalian pseudokinase tribbles family and is involved in multiple biological processes. However, the role of TRIB3 in renal cell carcinoma (RCC) remains unclear. In this study, we aimed to elucidate the biological functions of TRIB3 in RCC and explore its underlying mechanisms. TRIB3 expression and its correlation with clinicopathological features was evaluated in 123 patients with RCC. A series of cytological experiments were performed to clarify the biological functions of TRIB3, and potential molecular regulatory mechanisms were explored using transcriptome sequencing. TRIB3 expression was significantly elevated in RCC tissues compared to that in paracancerous tissues, and high expression of TRIB3 was correlated with both advanced tumor stage and unfavorable prognosis. TRIB3 knockdown markedly inhibited RCC cell proliferation, migration and invasion. Furthermore, overexpression of TRIB3 promoted RCC cell proliferation, migration, invasion and xenograft tumor growth. Notably, TRIB3 expression was modulated by hypoxia-inducible factor-1α (HIF-1α), which enhanced cell viability and invasiveness via targeting the MAPK signaling pathway. This study reveals the potential oncogenic role of TRIB3 in RCC pathogenesis and illustrates the mechanisms underlying TRIB3-mediated tumor progression, providing new insight into the development of TRIB3 as a tumor biomarker and therapeutic target.
Keywords: Tribbles pseudokinase 3, renal cell carcinoma, cell proliferation, cell invasion, mitogen-activated protein kinases