首页|SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

SETDB1-mediated CD147-K71 di-methylation promotes cell apoptosis in non-small cell lung cancer

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Protein post-translational modifications(PTMs)are at the heart status of cellular signaling events and broadly involved in tumor progression.CD147 is a tumor biomarker with various PTMs,promoting tumor metastasis and metabolism reprogramming.Nevertheless,the relationship between the PTMs of CD147 and apoptosis has not been reported.In our study,we produced a specific anti-CD147-K71 di-methylation(CD147-K71me2)antibody by immu-nizing with a di-methylated peptide and observed that the level of CD147-K71me2 in non-small cell lung cancer(NSCLC)tissues were lower than that in NSCLC adjacent tissues.SETDB1 was identified as the methyltransferase catalyzing CD147 to generate CD147-K71me2.RNA-seq showed that FOSB was the most significant differentially expressed gene(DEG)between wild-type CD147(CD147-WT)and K71-mutant CD147(CD147-K71R)groups.Subsequently,we found that CD147-K71me2 promoted the expression of FOSB by enhancing the phosphorylation of p38,leading to tumor cell apoptosis.In vivo experiments showed that CD147-K71me2 signif-icantly inhibited tumor progression by promoting cell apoptosis.Taken together,our findings indicate the inhibitory role of CD147-K71me2 in tumor progression from the perspective of post-translational modification,which is distinct from the pro-cancer function of CD147 itself,broadening our perspective on tumor-associated antigen CD147.

CD147 di-methylationCell apoptosisFOSBNon-small cell lung cancerSETDB1

Ming-Yan Shi、Yarong Wang、Ying Shi、Ruofei Tian、Xiaohong Chen、Hai Zhang、Ke Wang、Zhinan Chen、Ruo Chen

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National Translational Science Center for Molecular Medicine & Department of Cell Biology,Fourth Military Medical University,Xi'an,Shaanxi 710032,China

Science and Technology Project of Shaanxi Province,ChinaScience and Technology Project of Shaanxi Province,ChinaScience and Technology Project of Shaanxi Province,ChinaYoung Elite Scientist Sponsorship Program by Cast(China Association for Science and Technology)

2021 PT-0472022 PT-432022JQ-8742020QNRC001

2024

10.1016/j.gendis.2023.02.015

基因与疾病(英文)

基因与疾病(英文)

ISSN：
年,卷(期)：2024.11(2)
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