RNA-seq reveals co-dysregulated circular RNAs in the adenomyosis eutopic endometrium and endometrial–myometrial interface

Abstract

Background Uterine adenomyosis is associated with chronic pelvic pain, abnormal uterine bleeding, and infertility. The pathogenesis of adenomyosis is still unclear. Circular RNAs (circRNAs) have been implicated in several benign diseases and malignant tumors. We aimed to explore the co-dysregulated circular RNA profile in the eutopic endometrium and endometrial–myometrial interface (EMI) of adenomyosis. Methods Total RNA was extracted from the eutopic endometrium and EMI of 5 patients with adenomyosis and 3 patients without adenomyosis. Next-generation sequencing was performed to identify the circRNA expression profile of the two tissue types. Bioinformatics analysis was performed to predict circRNA-binding miRNAs and miRNA-binding mRNAs and construct ceRNA networks, and functional enrichment analysis was performed to predict the biological functions of circRNAs. Results Among the adenomyosis patients, 760 circRNAs were significantly upregulated and 119 circRNAs were significantly downregulated in the EMI of adenomyosis, while 47 circRNAs were significantly upregulated and 17 circRNAs were significantly downregulated in the eutopic endometrium of adenomyosis. We identified hsa_circ_0002144 and hsa_circ_0005806 as co-upregulated and hsa_circ_0079536 and hsa_circ_0024766 as co-downregulated in the eutopic endometrium and EMI. Bioinformatics analysis was performed to construct a ceRNA network of codifferentially expressed circRNAs. The MAPK signaling pathway is the most important signaling pathway involved in the function of the ceRNA network. Conclusions Co-dysregulated circRNAs were present in the eutopic endometrium and EMI of adenomyosis. MiRNA binding sites were observed for all of these circRNAs and found to regulate gene expression. Co-dysregulated circRNAs may induce the eutopic endometrial invagination process through the MAPK signaling pathway and promote the progression of adenomyosis.

Endometrial microbiota in women with and without adenomyosis: A pilot study

“…The Endometriosis Committee of the Chinese Medical Doctor Association of Obstetricians and Gynecologists defines ADS as an eutopic endometrium that invades and migrates into the uterine myometrium, a condition that affects 7-23% of women of reproductive age (García-Solares et al, 2018;Leng et al, 2020). The recognized mechanisms of ADS include the invasion of the endometrial basalis into the myometrium, microtrauma of the endometrialmyometrial interface, genetics, immune disorders, and inflammatory mediators (An et al, 2017;Vannuccini et al, 2017;Guo, 2020;Zhai et al, 2020;Guo et al, 2022). However, the clinical presentations of patients with ADS are heterogeneous, thus indicating that unknown pathological mechanisms may exist (Bourdon et al, 2021).…”

Exosomal MiR-92a-3p serves as a Promising Diagnostic Marker and Potential Therapeutic Target for Adenomyosis

“…Adenomyosis is a complex gynecological condition characterized by the infiltration of endometrial tissue into the uterine muscle, leading to significant morbidity among women 1,2 . Despite advancements in understanding its hormonal and genetic underpinnings, the molecular mechanisms, particularly the role of exosomal microRNAs (miRNAs), remain inadequately explored [3][4][5] . Therefore, the identification of clinical biomarkers to aid in the diagnosis of adenomyosis is of significant importance 6,7 .…”