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. 2022 Jul 15;22(1):293.
doi: 10.1186/s12905-022-01871-2.

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

Affiliations

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

Zhengchen Guo et al. BMC Womens Health. .

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.

Keywords: Adenomyosis; Endometrial–myometrial interface; Endometrium; Expression profile; RNA sequencing; circRNA.

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Conflict of interest statement

The authors declared that they have no competing interests.

Figures

Fig. 1
Fig. 1
Characteristics of the circular RNA expression profile in EMI tissues from patients of adenomyosis and control group. a The identified circRNAs in this study were compared with previously reported circRNAs in the circBase database. b Genomic origin of the identified circRNAs. c Box plots showing the distribution of differential expressed circRNAs. d Hierarchical clustering of the significantly differentially expressed circRNAs. ‘Red’ indicates higher expression, and ‘Blue’ indicates lower expression. ADS, adenomyosis; CON, control, EMI, endometrium–myometrium interface; circRNA, Circular RNA
Fig. 2
Fig. 2
Characteristics of the circular RNA expression profile in eutopic endometrium tissues from patients with adenomyosis and control group. a The identified circRNAs in this study were compared with previously reported circRNAs in the circBase database. b Genomic origin of the identified circRNAs. c Box plots showing the distribution of differential expressed circRNAs. d Hierarchical clustering of the significantly differentially expressed circRNAs. ‘Red’ indicates higher expression, and ‘Blue’ indicates lower expression. ADS, adenomyosis; CON, control; EN, eutopic endometrium; circRNA, Circular RNA
Fig. 3
Fig. 3
Co-dysregulated circRNAs and prediction of targeted RNA in eutopic endometrium and EMI. a Co-dysregulated circRNAs in eutopic endometrium and EMI. b Targeted miRNAs of co-dysregulated circRNAs. c Targeted mRNAs of co-dysregulated circRNAs targeted miRNAs. EMI_diff_circRNA, differential expressed circular RNAs in endometrium–myometrium interface; EN_diff_circRNA, differential expressed circular RNAs in eutopic endometrium
Fig. 4
Fig. 4
CeRNA network of co-dysregulated circRNAs. The mapping network included the 4 circRNAs with significant expression differences in the circRNA–miRNA network prediction. The blue ring consists of 1775 rounded rectangles representing the targeted genes
Fig. 5
Fig. 5
GO analysis of the potential targets of co-dysregulated circRNAs. GO, Gene ontology; BP, biological process; CC, cellular component; MF, molecular function
Fig. 6
Fig. 6
KEGG pathway analysis of the potential targets of co-dysregulated. The Bulb map shows the top 20 dysregulated KEGG pathways. KEGG, Kyoto Encyclopedia of Genes and Genome
Fig. 7
Fig. 7
The mapping network related with MAPK signaling pathway
Fig. 8
Fig. 8
Targeted genes of network in schematic diagram of the MAPK signaling pathway. Red star denotes targeted gene

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