ADORA2A promotes proliferation and inhibits apoptosis through PI3K/AKT pathway activation in colorectal carcinoma

Sci Rep. 2023 Nov 9;13(1):19477. doi: 10.1038/s41598-023-46521-1.

Abstract

The third most often diagnosed disease globally and the second most prevalent cause of cancer-related death is colorectal cancer (CRC). Numerous human malignancies have been identified to have high expression of ADORA2A. However, it is still ambiguous about its function in CRC. RNA-seq with stable transfected SETDB1 knockdown cells was used to identify differentially expressed genes. Further, knockdown of ADORA2A in CRC cell lines SW620 and HCT116 was performed with siRNA and over expression of ADORA2A in SW480 cells was conducted with plasmids. CCK8, colony formation, wound healing, and transwell assay were used to detect the effects of cell proliferation, migration, and invasion after knockdown and over expression of ADORA2A. Also, apoptosis was analyzed by flow cytometry, apoptosis-related proteins and key PI3K/AKT pathway proteins were detected using Western blotting. ADORA2A was identified after RNA-seq analysis and played an important role in CRC prognosis. ADORA2A was relatively high in SW620 and HCT116 cell lines compared to SW480 cell lines. ADORA2A knockdown in SW620 and HCT116 inhibited cell proliferation, migration, and invasion, while ADORA2A overexpression had the opposite effect. In addition, ADORA2A also impacted the expression of apoptosis-related proteins, including Bcl-2, Bax, Cleaved caspase-3 and Cleaved caspase-9, and reduced apoptosis. Furthermore, this process may include the PI3K/AKT signaling pathway. ADORA2A promotes CRC progression and inhibits apoptosis by the PI3K/AKT signaling pathway. It may contribute to the management and treatment of CRC.

MeSH terms

  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Colorectal Neoplasms* / pathology
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt* / metabolism

Substances

  • Phosphatidylinositol 3-Kinases
  • Proto-Oncogene Proteins c-akt
  • ADORA2A protein, human