TRIB3 Promotes Laryngeal Cancer Progression via Regulating Ubiquitination of PPARα

Laryngeal cancer is a prevalent malignancy within the head and neck region, and its incidence is progressively rising. This study aimed to examine the role of TRIB3 in laryngeal cancer. TU212 and TU686 cell lines were transfected with a TRIB3-targeting lentivirus. Colony formation, flow cytometry, and wound scratch healing assay were used to detect cell proliferation, apoptosis, and migration, respectively. TRIB3 expression levels were quantified using fluorescence real-time quantitative polymerase chain reaction (qRT-PCR). The protein expression levels of TRIB3 and PPARα were analyzed through Western blotting. The effect of TRIB3 knockdown on tumor growth was further examined using a nude mouse xenograft model. Cycloheximide (CHX) and MG-132 were used to treat cells, then co-immunoprecipitation (CO-IP) assays were employed to explore the interaction between TRIB3 and PPARα. Additionally, the effect of TRIB3 knockdown on PPARα ubiquitination was examined by CO-IP. Our results demonstrated that TRIB3 knockdown suppressed cell proliferation and migration while promoting cell apoptosis. In vivo experiment corroborated the suppressive effect of TRIB3 knockdown on cell proliferation, presented as suppressed tumor growth. Furthermore, CHX treatment suppressed the expression of PPARα while TRIB3 knockdown promoted PPARα expression in TU212 and TU686 cells. CO-IP assay and IF staining confirmed the interaction of TRIB3 and PPARα. MG-132 treatment promoted the expression of PPARα, and TRIB3 knockdown obviously promoted PPARα expression in TU212 and TU686 cells. CO-IP assay confirmed TRIB3 deubiquitinates and stabilizes PPARα. Our results suggest that TRIB3 knockdown inhibits the proliferation of laryngeal cancer cells. The mechanism of action is related to the regulation of ubiquitination of PPARα. Our research provide a novel insights into the treatment of laryngeal cancer.