TRIM66 hastens the malignant progression of non-small cell lung cancer via modulating MMP9-mediated TGF-β/SMAD pathway.

Wenyu Chen, Ye Zhang, Zhixian Fang, Weibo Qi, Yufen Xu

Cytokine 2022 May

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To investigate regulatory function and underlying mechanism of TRIM66 in non-small cell lung cancer (NSCLC). TRIM66 and MMP9 expression in NSCLC cells and tissues was assayed via qRT-PCR and western blot. CCK-8, colony formation, Transwell and flow cytometry assays were conducted to measure cell functional alternations in NSCLC. Western blot was employed to measure expression as well as phosphorylation levels of epithelial-mesenchymal transition-(EMT) and TGF-β/SMAD pathways-related proteins. Co-immunoprecipitation (Co-IP) assay was done to probe interaction between TRIM66 and MMP9. Xenograft in vivo experiment and tumor metastasis model in nude mice were utilized to investigate effects of TRIM66 on tumor growth of NSCLC. TRIM66 and MMP9 were conspicuously highly expressed in NSCLC cells and tissues. High TRIM66 level was markedly correlated with metastasis. Silencing TRIM66 prominently repressed the proliferation, migration and invasion of transfected cells, while inducing cell apoptosis. Whereas forced expression of TRIM66 exerted the opposite effect. The aberrant expression of TRIM66 modulated EMT pathway. TRIM66 also regulated MMP9 expression, and the interaction between them was validated by Co-IP assay. Overexpression of MMP9 could activate TGF-β/SMAD pathway. Rescue experiments manifested that si-MMP9 or SB431542 could partially reverse phenotypes induced by TRIM66. In vivo experiments revealed that silencing TRIM66 could hamper NSCLC tumor growth and metastasis. TRIM66 and MMP9 were up-regulated in NSCLC. TRIM66 facilitated the malignant progression of NSCLC through modulating MMP9-mediated TGF-β/SMAD pathway. Copyright © 2022. Published by Elsevier Ltd.

Citation

Wenyu Chen, Ye Zhang, Zhixian Fang, Weibo Qi, Yufen Xu. TRIM66 hastens the malignant progression of non-small cell lung cancer via modulating MMP9-mediated TGF-β/SMAD pathway. Cytokine. 2022 May;153:155831