Presentation Authors: Baoan Hong*, Kaifang Ma, Jingcheng Zhou, Haibiao Xie, Kenan Zhang, Lei Li, Kan Gong, Beijing, China, People's Republic of
Introduction: 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.
Methods: 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. KEGG pathway analysis was used to clarify the physiological functions and signaling pathways related to the DEGs in RCC cell lines. Cells were cultured and treated with Cobalt chloride (CoCl2) for 0 h, 2 h, 4 h, 6 h, 12 h, 24 h, 48 h or 72 h. Then, the expression of TRIB3, HIF-1Î± and HIF-2Î± was assessed. The HIF-1Î± promoter region was inserted into a pLVX basic vector. The Dual-Luciferase Reporter Assay System was used in the luciferase reporter assays.
Results: 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-1Î± (HIF-1Î±), which enhanced cell viability and invasiveness via targeting the MAPK signaling pathway.
Conclusions: 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.
Source of Funding: National Natural Science Foundation of China (grant 81572506)Special Health Development Research Project of Capital (grant 2016-2-4074)Fundamental Research Funds for the Central Universities (grant BMU2018JI002)