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Updated: Aug 10, 2025

Identification of RNAs Engaged in Direct RNA-RNA Interaction with a Long Non-Coding RNA
Published on: July 9, 2021
Construction of PARPi Resistance-related Competing Endogenous RNA Network
Lili Kong1, Jiaqi Xu2,3, Lijun Yu1
1Beijing Rehabilitation Hospital, Capital Medical University, Beijing, China.
Abstract:
Ovarian cancer is a kind of common gynecological malignancy in women. PARP inhibitors (PARPi) have been approved for ovarian cancer treatment. However, the primary and acquired resistance have limited the application of PARPi. The mechanisms remain to be elucidated. In this study, we characterized the expression profiles of mRNA and nonconding RNAs (ncRNAs) and constructed the regulatory networks based on RNA sequencing in PARPi Olaparib-induced ovarian cancer cells. We found that the functions of the differentially expressed genes were enriched in "PI3K/AKT signaling pathway," "MAPK signaling pathway" and "metabolic process". The functions of DELs (cis) were enriched in "Human papillomavirus infection""tight junction" "MAPK signaling pathway". As the central regulator of ceRNAs, the differentially expressed miRNAs were enriched in "Human papillomavirus infection" "MAPK signaling pathway" "Ras signaling pathway". According to the degree of interaction, we identified 3 lncRNAs, 2 circRNAs, 7 miRNAs, and 12 mRNA as the key regulatory ceRNA axis, in which miR-320b was the important mediator. Here, we revealed the key regulatory lncRNA (circRNA)-miRNA-mRNA axis and their involved pathways in the PARPi resistant ovarian cancer cells. These findings provide new insights into exploring the ceRNA regulatory networks and developing new targets for PARPi resistance.
Insights
Poly (ADP-ribose) polymerase inhibitors (PARPi) resistance in ovarian cancer is a challenge. This study identified key RNA networks and pathways, revealing potential new targets for overcoming PARPi resistance.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Ovarian cancer is a common gynecological malignancy.
- Poly (ADP-ribose) polymerase inhibitors (PARPi) are used for treatment, but resistance limits their efficacy.
- Mechanisms underlying PARPi resistance require further elucidation.
Purpose of the Study:
- To characterize RNA expression profiles and construct regulatory networks in PARPi-resistant ovarian cancer cells.
- To identify key regulatory ceRNA axes and their involved pathways in PARPi resistance.
- To provide insights for developing novel therapeutic targets against PARPi resistance.
Main Methods:
- RNA sequencing was performed on PARPi (Olaparib)-induced ovarian cancer cells.
- Differential expression analysis of mRNAs, lncRNAs, circRNAs, and miRNAs was conducted.
- RNA regulatory networks, particularly ceRNA networks, were constructed and analyzed.
Main Results:
- Differentially expressed genes were enriched in PI3K/AKT, MAPK signaling, and metabolic pathways.
- Key regulatory ceRNA axes involving lncRNAs, circRNAs, miRNAs, and mRNAs were identified.
- miR-320b was identified as a crucial mediator in these regulatory networks.
Conclusions:
- Key regulatory lncRNA-circRNA-miRNA-mRNA axes and their associated pathways were revealed in PARPi-resistant ovarian cancer.
- These findings offer new perspectives on ceRNA regulatory networks in drug resistance.
- The identified axes and pathways represent potential targets for overcoming PARPi resistance in ovarian cancer.
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