Molecular Mechanisms Underlying Regulations Of CCL18 Mediated Post-translational Modifications And Transcription

Lung cancer is one of the fastest growing morbidity and mortality rates in the world,and it is one of the most important malignant tumors for population health and life threat.The analysis of the function and activity regulation mechanism of key molecules involved in its pathogenesis contributes to the promotion of lung adenocarcinoma in China.Early diagnosis of cancer and provide clues for finding new therapeutic targets.Tumor-associated macrophages(TAMs)are one of the most common types of immune cells in the tumor microenvironment,and their secreted chemokine CCL18 alters tumor cell plasticity and promotes its metastatic potential.CCL18 is a special type of cell chemokine that is highly expressed in lung cancer,breast cancer,and other tumor tissues.It not only promotes the transcription and protein expression levels of multiple genes in tumor cells,but also induces the activity of protein kinases and acetyltransferases.Change,which is bound to accompany its substrate phosphorylation,acetylation level changes,thereby promoting the occurrence and development of malignant tumors.In this paper,we hope to identify CCL18-mediated post-translational modification of proteins with important functions and to analyze their possible roles in the development and progression of lung adenocarcinoma by using non-small cell lung adenocarcinoma cell line A549 as a research material Regulatory mechanism.We performed SILAC labeling on non-small cell lung adenocarcinoma cell line A549 using an in vitro isotope labeling technique.Using quantitative proteomic analysis,we identified 1,424 acetylation sites and 3,659 phosphorylation sites,preliminarily establishing CCL18 before and after short-term treatment.Protein post-translational modification profile,and the detection and validation of mass spectrometry identification by immunoblotting and other methods,the results show that CCL18 treatment can induce the increase of acetylation level of histone specific sites in A549 cells,from the perspective of epigenetics This shows that CCL18 may regulate the transcriptional level of intracellular genes.For this purpose,we further performed transcriptome sequencing of the three groups of CCL18-treated and untreated A549 cells.Preliminary data analysis showed that CCL18 can promote transcription of multiple target genes including CD274,FOS,EGR1,FAM83 A and FOSB,and qPCR detection.The results showed that the transcriptome sequencing results.Previous studies have shown that these four genes play an important role in tumor immunity,tumor cell proliferation,migration and metabolism,which further proves that CCL18 can regulate tumor cells through different ways and pathways.The development of these researches has laid a solid foundation for our later in-depth and accurate analysis of the role of CCL18 in tumorigenesis and development.