Research Paper Volume 13, Issue 10 pp 14289—14303
Autophagy deficiency downregulates O6methylguanine-DNA methyltransferase and increases chemosensitivity of liver cancer cells
- 1 Tumor Immunology and Gene Therapy Center, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai 200438, China
- 2 Institutes of Translational Medicine, Shanghai University, Shanghai 200444, China
Received: December 10, 2020 Accepted: March 4, 2021 Published: May 24, 2021https://doi.org/10.18632/aging.203044
How to Cite
Copyright: © 2021 Hou et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
It is known that autophagy-deficient cells are prone to DNA damage, but the specific role of autophagy in DNA damage repair is not fully known. Here, we show that autophagy-deficient liver cancer cells exhibit increased DNA damage caused by the chemotherapeutic agent epirubicin. Autophagy deficiency promotes downregulation of the DNA repair enzyme O6methylguanine-DNA methyltransferase (MGMT) in liver cancer cells. However, autophagy induction with epirubicin had no impact on MGMT gene or protein expression in liver cancer cells. In the absence of autophagy, the chemosensitivity of liver cancer cells was increased, but this was reversed by MGMT overexpression, indicating that autophagy mediates resistance to chemotherapy in liver cancer cells via MGMT. These findings demonstrate a direct link between autophagy, MGMT, and DNA damage repair in liver cancer cells, and show that MGMT not only regulates chemosensitivity to alkylating agents, but may also be involved in other DNA damage repair processes in autophagy-deficient cells.