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Sci Rep ; 14(1): 11670, 2024 05 22.
Article in English | MEDLINE | ID: mdl-38778047

ABSTRACT

Colorectal cancer (CRC) arises via the progressive accumulation of dysregulation in key genes including oncogenes and tumor-suppressor genes. Prostaglandin-endoperoxide synthase 2 (PTGS2, also called COX2) acts as an oncogenic driver in CRC. Here, we explored the upstream transcription factors (TFs) responsible for elevating PTGS2 expression in CRC cells. The results showed that PTGS2 silencing repressed cell growth, migration and invasion in HCT116 and SW480 CRC cells. The two fragments (499-981 bp) and (1053-1434 bp) were confirmed as the core TF binding profiles of the PTGS2 promoter. PTGS2 expression positively correlated with RUNX1 level in colon adenocarcinoma (COAD) samples using the TCGA-COAD dataset. Furthermore, RUNX1 acted as a positive regulator of PTGS2 expression by promoting transcriptional activation of the PTGS2 promoter via the 1086-1096 bp binding motif. In conclusion, our study demonstrates that PTGS2 upregulation induced by the TF RUNX1 promotes CRC cell growth, migration and invasion, providing an increased rationale for the use of PTGS2 inhibitors in CRC prevention and treatment.


Subject(s)
Cell Movement , Cell Proliferation , Colorectal Neoplasms , Core Binding Factor Alpha 2 Subunit , Cyclooxygenase 2 , Gene Expression Regulation, Neoplastic , Neoplasm Invasiveness , Promoter Regions, Genetic , Up-Regulation , Humans , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/genetics , Core Binding Factor Alpha 2 Subunit/metabolism , Core Binding Factor Alpha 2 Subunit/genetics , Cell Movement/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Colorectal Neoplasms/metabolism , Cell Proliferation/genetics , Cell Line, Tumor , HCT116 Cells
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