Article ; Online: Neil 1 deficiency facilitates chemoresistance through upregulation of RAD18 expression in ovarian cancer stem cells.
Biochemical and biophysical research communications
2024 Volume 712-713, Page(s) 149907
Abstract: Over the past decades, cancer stem cells (CSCs) have emerged as a critical subset of tumor cells associated with tumor recurrence and resistance to chemotherapy. Understanding the mechanisms underlying CSC-mediated chemoresistance is imperative for ... ...
| Abstract | Over the past decades, cancer stem cells (CSCs) have emerged as a critical subset of tumor cells associated with tumor recurrence and resistance to chemotherapy. Understanding the mechanisms underlying CSC-mediated chemoresistance is imperative for improving cancer therapy outcomes. This study delves into the regulatory role of NEIL1, a DNA glycosylase, in chemoresistance in ovarian CSCs. We first observed a decreased expression of NEIL1 in ovarian CSCs, suggesting its potential involvement in CSC regulation. Using pan-cancer analysis, we confirmed the diminished NEIL1 expression in ovarian tumors compared to normal tissues. Furthermore, NEIL1 downregulation correlated with an increase in stemness markers and enrichment of CSCs, highlighting its role in modulating CSC phenotype. Further mechanistic investigation revealed an inverse correlation between NEIL1 and RAD18 expression in ovarian CSCs. NEIL1 depletion led to heightened RAD18 expression, promoting chemoresistance possibly via enhancing Translesion DNA Synthesis (TLS)-mediated DNA lesion bypass. Moreover, dowregulation of NEIL1 results in reduced DNA damage accumulation and suppressed apoptosis in ovarian cancer. Overall, our findings unveil a novel mechanism involving NEIL1 and RAD18 in regulating chemoresistance in ovarian CSCs. Targeting this NEIL1-RAD18 axis may offer promising therapeutic strategies for combating chemoresistance and improving ovarian cancer treatment outcomes. |
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| MeSH term(s) | Humans ; Female ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/drug therapy ; Drug Resistance, Neoplasm/genetics ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Up-Regulation ; DNA Glycosylases/metabolism ; DNA Glycosylases/genetics ; Cell Line, Tumor ; DNA-Binding Proteins/metabolism ; DNA-Binding Proteins/genetics ; Gene Expression Regulation, Neoplastic ; Ubiquitin-Protein Ligases/genetics ; Ubiquitin-Protein Ligases/metabolism ; DNA Damage ; Apoptosis/drug effects ; Apoptosis/genetics |
| Chemical Substances | DNA Glycosylases (EC 3.2.2.-) ; NEIL1 protein, human (EC 3.2.2.-) ; RAD18 protein, human ; DNA-Binding Proteins ; Ubiquitin-Protein Ligases (EC 2.3.2.27) |
| Language | English |
| Publishing date | 2024-04-12 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 205723-2 |
| ISSN | 1090-2104 ; 0006-291X ; 0006-291X |
| ISSN (online) | 1090-2104 ; 0006-291X |
| ISSN | 0006-291X |
| DOI | 10.1016/j.bbrc.2024.149907 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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