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Updated: Jan 16, 2026
Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays
Published on: February 24, 2023
DNA Damage and Repair in Ovarian Cancer: Focus on MicroRNAs
Katarzyna D Arczewska1, Agnieszka Piekiełko-Witkowska1
1Department of Biochemistry and Molecular Biology, Centre of Postgraduate Medical Education, 01-813 Warsaw, Poland.
Abstract:
Ovarian cancer (OvCa) is one of the most life-threatening female malignancies that affects 300,000 women annually worldwide. Impaired mechanisms of DNA repair are the leading cause of mutations underlying the OvCa development. microRNAs are short non-coding RNAs that regulate the expression of genes by binding to their transcripts and inducing mRNA degradation or inhibition of translation. Here, we review the miRNA-mediated dysregulation of genes involved in DNA damage response (DDR) and DNA repair pathways in OvCa. Apparently, miRNAs are capable of targeting the crucial mediators of DDR (e.g., miR-203a-3p targeting ATM (Ataxia Telangiectasia Mutated)), homologous repair (such as BRCA1 targeted by miR-9, miR-1255b, miR-193b, and miR-148b), non-homologous end joining (with RNF8 being regulated by miR-214), nucleotide excision repair (involving DDB2 targeted by miR-328-3p), or translesion DNA synthesis (involving RAD18, participating also in homologous repair and targeted by miR-379-5p). We also discuss miRNAs (such as miR-519a-3p, let-7e, miR-216b), which affect responses to OvCa therapy by targeting PARP1 (Poly(ADP-Ribose) Polymerase-1). Finally, we also discuss why, despite the identification of multiple miRNAs capable of regulating DNA repair genes, as well as those involved in the response to therapy, no miRNA-based drugs have been approved for OvCa treatment in clinics.
Insights
microRNAs (miRNAs) dysregulate DNA repair genes in ovarian cancer (OvCa), impacting DNA damage response and therapy effectiveness. Despite identified targets, no miRNA-based OvCa drugs are currently approved.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Ovarian cancer (OvCa) is a leading cause of female cancer deaths worldwide.
- Defective DNA repair mechanisms drive OvCa development and progression.
- microRNAs (miRNAs) are key regulators of gene expression involved in cellular processes.
Purpose of the Study:
- To review miRNA-mediated dysregulation of DNA damage response (DDR) and DNA repair pathways in OvCa.
- To explore the role of specific miRNAs in targeting key DNA repair genes.
- To discuss the implications of miRNA dysregulation for OvCa therapy response.
Main Methods:
- Literature review of studies on miRNA regulation of DNA repair genes in OvCa.
- Analysis of specific miRNA interactions with DDR and DNA repair mediators.
- Examination of miRNAs affecting response to OvCa therapies, including PARP1 inhibitors.
Main Results:
- miRNAs target crucial DDR mediators like ATM (e.g., miR-203a-3p).
- Specific miRNAs regulate homologous repair (BRCA1), non-homologous end joining (RNF8), nucleotide excision repair (DDB2), and translesion synthesis (RAD18).
- Certain miRNAs (e.g., miR-519a-3p, let-7e, miR-216b) influence OvCa therapy response by targeting PARP1.
Conclusions:
- miRNA dysregulation significantly impacts DNA repair pathways in OvCa.
- While numerous miRNAs target DNA repair genes and affect therapy response, clinical translation remains a challenge.
- Further research is needed to develop effective miRNA-based therapeutic strategies for OvCa.
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