TRIM11 promotes lymphomas by activating the β-catenin signaling and Axin1 ubiquitination degradation

2019 
Abstract Objective Lymphoma, a malignant tumor, is mainly characterized by painless lymph node enlargement and hepatosplenomegaly. At present, lymphoma is mainly treated by radiation, chemical drugs, bone marrow transplantation and surgery. However, due to the high degree of heterogeneity, lymphomas are highly different in terms of treatment intensity and prognosis. This study is designed to investigate the function of tripartite motif-containing 11 (TRIM11) in lymphomas. Methods The expression of TRIM11 in lymphoma tissues and multiple lymphoma cell lines was respectively detected by microarray immunohistochemistry, real-time PCR and Western blotting. After TRIM11 knockdown, overexpression, or β-catenin inhibitor XAV939 treatment, proliferation, apoptosis and cell cycle progression, as well as expression of related-genes were detected. Next, Co-Immunoprecipitation (Co-IP) and ubiquitination detection were performed. Results Elevated expression of tripartite motif-containing 11 (TRIM11) was observed in lymphoma tissues and multiple lymphoma cell lines (Raji, Jurkat, U937 and Hut78). Knockdown of TRIM11 in lymphoma cells significantly suppressed cell proliferation and prevented cell cycle progression from entering S or G2 phase. Concurrently, the expression of β-catenin, Cyclin D1 and c-Myc proteins in TRIM11-silenced lymphoma cells was decreased, while Axin1 was increased. In addition, TRIM11 overexpression had an opposite effect to TRIM11 knockdown, and a β-catenin inhibitor, XAV939, potently attenuated the induction of TRIM11 on lymphoma cells. Co-IP assay showed the interaction of TRIM11 and Axin1, and TRIM11 knockdown inhibited Axin1 ubiquitination degradation. Conclusions Together all, the results suggested that TRIM11 may be an oncogene in lymphomas, which involving the activation of the β-catenin signaling and the ubiquitination degradation of Axin1.
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