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Current Genomics

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ISSN (Print): 1389-2029
ISSN (Online): 1875-5488

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Research Article

Construction of PARPi Resistance-related Competing Endogenous RNA Network

Author(s): Lili Kong, Jiaqi Xu, Lijun Yu, Shuo Liu, Zongjian Liu and Juanjuan Xiang*

Volume 23, Issue 4, 2022

Published on: 10 June, 2022

Page: [262 - 274] Pages: 13

DOI: 10.2174/1389202923666220527114108

open access plus

Abstract

Objective: 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.

Methods: 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 Olaparibinduced ovarian cancer cells.

Results: 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.

Conclusion: 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.

Keywords: Ovarian cancer, PARPi resistance, ceRNA network, mRNA, DNA, SSB.

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Graphical Abstract

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