RUNX1 诱导的 PTGS2 上调增强了结直肠癌细胞的生长、迁移和侵袭。

RUNX1-induced upregulation of PTGS2 enhances cell growth, migration and invasion in colorectal cancer cells.

机构信息

Department of Gastrointestinal Surgery, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, No. 7 Weiwu Road, Zhengzhou, 450003, Henan, China.

Hepatobiliary Gastrointestinal Surgery Department, Red Star Hospital of the 13th Division of Xinjiang Production and Construction Corps, Hami, 839000, The Xinjiang Uygur Autonomous Region, China, China.

出版信息

Sci Rep. 2024 May 22;14(1):11670. doi: 10.1038/s41598-024-60296-z.

DOI:10.1038/s41598-024-60296-z

PMID:38778047

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11111780/

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.

摘要

结直肠癌（CRC）是通过关键基因（包括癌基因和肿瘤抑制基因）的失调逐渐积累而发生的。前列腺素内过氧化物合酶 2（PTGS2，也称为 COX2）在 CRC 中作为致癌驱动因子发挥作用。在这里，我们探讨了导致 CRC 细胞中 PTGS2 表达升高的上游转录因子（TF）。结果表明，PTGS2 沉默抑制了 HCT116 和 SW480 CRC 细胞的生长、迁移和侵袭。两个片段（499-981 bp）和（1053-1434 bp）被确认为 PTGS2 启动子的核心 TF 结合图谱。使用 TCGA-COAD 数据集，PTGS2 的表达与结肠腺癌（COAD）样本中的 RUNX1 水平呈正相关。此外，RUNX1 通过促进 1086-1096 bp 结合基序的 PTGS2 启动子转录激活，作为 PTGS2 表达的正调节剂。总之，我们的研究表明，由 TF RUNX1 诱导的 PTGS2 上调促进了 CRC 细胞的生长、迁移和侵袭，为使用 PTGS2 抑制剂预防和治疗 CRC 提供了更多的理由。