Yu-Hong Li1, Ying-Xue Li1, Mu Li2, Shao-Wei Song3, Yang Ge2, Jun-Yi Jin2, Xiao-Ying Li3, Xiao-Dong Tan2, Jing Ye4. 1. Department of Pathology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China. 2. Department of General Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China. 3. Department of General Surgery, the First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110004, China. 4. Department of Pathology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, China. Electronic address: yejing67_lcph@163.com.
Abstract
AIMS: The regulation of the Ras-ERK pathway is the crucial point in pancreatic carcinogenesis, and the Ras kinase is an essential regulatory upstream signal molecule of the ERK1/2 pathway. H3K9ac is a vital histone modification, but its specific role in pancreatic cancer remains unclear. This research aims to study whether the modification level of H3K9ac can regulate the characteristic phenotype of the pancreatic cancer cells by affecting the downstream expression, proliferation, migration, and other related genes. MAIN METHODS: The RasG12V/T35S were used to transfect pancreatic cancer cells, and the levels of phosphorylated ERK1/2 and H3K9ac were detected by western blotting. The colony formation assay, transwell assay, and chromatin immunoprecipitation assay were used to study cell viability, migration, and the downstream genes of the ERK1/2 pathway. KEY FINDINGS: The results showed that Ras ERK1/2 reduced H3K9ac expression in ASPC-1 cells, and H3K9ac significantly repressed the viability of cells, colony formation, and ASPC-1 cell movement induced by Ras ERK1/2. Besides, HDAC1 silencing increased H3K9ac expression, and changed the effect of Ras ERK1/2 on ASPC-1 cells proliferation, its movement, and mRNAs of ERK1/2 downstream genes. Moreover, Ras ERK1/2 inhibited H3K9ac expression by the degradation of PCAF via MDM2. SIGNIFICANCE: Ras ERK1/2 promotes pancreatic carcinogenesis cell movement, through down-regulating H3K9ac via MDM2 mediated PCAF degradation.
AIMS: The regulation of the Ras-ERK pathway is the crucial point in pancreatic carcinogenesis, and the Ras kinase is an essential regulatory upstream signal molecule of the ERK1/2 pathway. H3K9ac is a vital histone modification, but its specific role in pancreatic cancer remains unclear. This research aims to study whether the modification level of H3K9ac can regulate the characteristic phenotype of the pancreatic cancer cells by affecting the downstream expression, proliferation, migration, and other related genes. MAIN METHODS: The RasG12V/T35S were used to transfect pancreatic cancer cells, and the levels of phosphorylated ERK1/2 and H3K9ac were detected by western blotting. The colony formation assay, transwell assay, and chromatin immunoprecipitation assay were used to study cell viability, migration, and the downstream genes of the ERK1/2 pathway. KEY FINDINGS: The results showed that Ras ERK1/2 reduced H3K9ac expression in ASPC-1 cells, and H3K9ac significantly repressed the viability of cells, colony formation, and ASPC-1 cell movement induced by Ras ERK1/2. Besides, HDAC1 silencing increased H3K9ac expression, and changed the effect of Ras ERK1/2 on ASPC-1 cells proliferation, its movement, and mRNAs of ERK1/2 downstream genes. Moreover, Ras ERK1/2 inhibited H3K9ac expression by the degradation of PCAF via MDM2. SIGNIFICANCE: Ras ERK1/2 promotes pancreatic carcinogenesis cell movement, through down-regulating H3K9ac via MDM2 mediated PCAF degradation.