Construction of a focal adhesion signaling pathway-related ceRNA network in pelvic organ prolapse by transcriptome analysis

Xia Yu; Li He; Ying Chen; Wenyi Lin; Hong Liu; Xiu Yang; Ying Ye; Xuemei Zheng; Zhenglin Yang; Yonghong Lin

doi:10.3389/fgene.2022.996310

Construction of a focal adhesion signaling pathway-related ceRNA network in pelvic organ prolapse by transcriptome analysis

Front Genet. 2022 Sep 13:13:996310. doi: 10.3389/fgene.2022.996310. eCollection 2022.

Authors

Xia Yu¹, Li He², Ying Chen², Wenyi Lin³, Hong Liu⁴, Xiu Yang⁴, Ying Ye⁴, Xuemei Zheng², Zhenglin Yang⁵, Yonghong Lin²

Affiliations

¹ Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
² Department of Obstetrics and Gynecology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
³ Department of Medical Pathology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁴ Department of Surgical, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
⁵ Sichuan Provincial Key Laboratory for Human Disease Gene Study and Institute of Laboratory Medicine, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China.

Abstract

Objective: Pelvic organ prolapse (POP) affects a large proportion of adult women, but the pathogenesis of POP remains unclear. The increase in global population aging will impose a substantial medical burden. Herein, we aimed to explore the related RNAs regulating the occurrence of POP and provide potential therapeutic targets. Method: Tissue biopsies were collected from the anterior vaginal wall of six women with POP and six matched subjects without POP. The profiles of mRNAs, circRNAs, lncRNAs, and miRNAs were obtained by whole transcriptome RNA sequencing. Result: The findings revealed that 71 circRNAs, 76 known lncRNAs, 84 miRNAs, and 931 mRNAs were significantly altered (p < 0.05 and |log2FC| > 1). GO and KEGG enrichment analyses indicated that the differentially expressed genes (DEGs) were mainly enriched in the focal adhesion signaling pathway. FLT, ITGA9, VEGFD, PPP1R12B, and ROCK2 were identified as focal adhesion signaling pathway-related hub genes by protein-protein interaction network analysis. Based on the relationships between the DEGs and miRNA, lncRNA and circRNA targets, we constructed a focal adhesion signaling pathway-related ceRNA network. The ceRNA network includes hsa_circ_0002190/hsa_circ_0046843/lnc-CARMN -miR-23a-3p - ROCK2 and hsa_circ_0001326/hsa_circ_0007733/lnc-AC107959/lnc-TPM1-AS - miR-205-5p - ROCK2/PPP1R12B/VEGFD. Moreover, abnormalities in the cytoskeleton in fibroblasts from individuals with POP were observed. Conclusion: In this study, a focal adhesion signaling pathway-related ceRNA network was constructed, and this network may serve as a target for finding suitable drugs for the treatment of POP.

Keywords: PPI; competing endogenous RNA; focal adhesion signaling pathway; pelvic organ prolapse; whole transcriptome RNA sequencing.