Aldolase A promotes cervical cancer cell radioresistance by regulating the glycolysis and DNA damage after irradiation

Cancer Biol Ther. 2023 Dec 31;24(1):2287128. doi: 10.1080/15384047.2023.2287128. Epub 2023 Nov 27.

Abstract

Radioresistance is the major obstacle that affects the efficacy of radiotherapy which is an important treatment for cervical cancer. By analyzing the databases, we found that aldolase A (ALDOA), which is a key enzyme in metabolic reprogramming, has a higher expression in cervical cancer patients and is associated with poor prognosis. We detected the expression of ALDOA in the constructed cervical cancer radioresistance (RR) cells by repetitive irradiation and found that it was upregulated compared to the control cells. Functional assays were conducted and the results showed that the knockdown of ALDOA in cervical cancer RR cells inhibited the proliferation, migration, and clonogenic abilities by regulating the cell glycolysis. In addition, downregulation of ALDOA enhanced radiation-induced apoptosis and DNA damage by causing G2/M phase arrest and further promoted radiosensitivity of cervical cancer cells. The functions of ALDOA in regulating tumor radiosensitivity were also verified by the mouse tumor transplantation model in vivo. Therefore, our study provides new insights into the functions of ALDOA in regulating the efficacy of radiotherapy and indicates that ALDOA might be a promising target for enhancing radiosensitivity in treating cervical cancer patients.

Keywords: ALDOA; DNA damage; cervical cancer; glycolysis; radioresistance; radiotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • DNA Damage
  • Female
  • Fructose-Bisphosphate Aldolase* / genetics
  • Fructose-Bisphosphate Aldolase* / metabolism
  • Gene Expression Regulation, Neoplastic
  • Glycolysis
  • Humans
  • Mice
  • Radiation Tolerance / genetics
  • Uterine Cervical Neoplasms* / genetics
  • Uterine Cervical Neoplasms* / pathology
  • Uterine Cervical Neoplasms* / radiotherapy

Substances

  • Fructose-Bisphosphate Aldolase
  • ALDOA protein, human

Grants and funding

This work was supported by Henan Province Colleges and Universities Innovative Talent Support Program (No. 21HASTIT044), Young and middle-aged subject leader of Henan Provincial Health Commission (No. HNSWJW-2022001), Henan Province Young and Middle-aged Health Science and Technology Innovative Talent Training Project (No. YXKC2020039), Central Plains Youth Top Talent Project (No. ZYYCYU202012169), High-level Talents Return to China for Research Funding Project, Henan Province University Major Research Project (No. 22A320055), Henan Medical Education Research Project (No. Wjlx2020062), Zhengzhou University clinical medicine first-class discipline talent training program (Outstanding young talents) and National Natural Science Foundation of China (No. 82303343)..