Research Paper|Volume 15, Issue 16|pp 8275—8297

Integrative analysis links autophagy to intrauterine adhesion and establishes autophagy-related circRNA-miRNA-mRNA regulatory network

Xiaotong Peng^1,², Yiping Zhu¹, Tao Wang¹, Shuo Wang³, Jing Sun¹

¹Shanghai Key Laboratory of Maternal Fetal Medicine, Shanghai Institute of Maternal-Fetal Medicine and Gynecologic Oncology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China
²Department of Gynaecology and Obstetrics, Xiangya Hospital, Central South University, Changsha 410008, China
³Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200233, China

* Equal contribution

Received: April 18, 2023Accepted: July 6, 2023Published: August 23, 2023

https://doi.org/10.18632/aging.204969

Copyright: © 2023 Peng et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Intrauterine adhesion (IUA) is a troublesome complication characterized with endometrial fibrosis after endometrial trauma. Increasing number of investigations focused on autophagy and non-coding RNA in the pathogenesis of uterine adhesion, but the underlying mechanism needs to be further studied.

Methods: mRNA expression profile and miRNA expression profile were obtained from Gene Expression Omnibus database. The autophagy related genes were low. Venn diagram was used to set the intersection of autophagy genes and DEGs to obtain ARDEGs. Circbank was used to select hub autophagy-related circRNAs based on ARDEMs. Then, the differentially expressed autophagy-related genes, miRNAs and circRNAs were analyzed by functional enrichment analysis, and protein-protein interaction network analysis. Finally, the expression levels of hub circRNAs and hub miRNAs were validated through RT-PCR of clinical intrauterine adhesion samples. In vitro experiments were investigated to explore the effect of hub ARCs on cell autophagy, myofibroblast transformation and collagen deposition.

Results: 11 autophagy-related differentially expressed genes (ARDEGs) and 41 differentially expressed miRNA (ARDEMs) compared between normal tissues and IUA were identified. Subsequently, the autophagy-related miRNA-mRNA network was constructed and hub ARDEMs were selected. Furthermore, the autophagy-related circRNA-miRNA-mRNA network was established. According to the ranking of number of regulated ARDEMs, hsa-circ-0047959, hsa-circ-0032438, hsa-circ-0047301 were regarded as the hub ARCs. In comparison of normal endometrial tissue, all three hub ARCs were upregulated in IUA tissue. All hub ARDEMs were downregulated except has-miR-320c.

Conclusions: In the current study, we firstly constructed autophagy-related circRNA-miRNA-mRNA regulatory network and identified hub ARCs and ARDEMs had not been reported in IUA.