Current and Future Roles of Circular RNAs in Normal and Pathological Endometrium

Tu, Jiajie; Yang, Huan; Chen, Yu; Chen, He; Li, Zhe; Li, Lei; Zhang, Yuanyuan; Chen, Xiaochun; Yu, Zhiying

doi:10.3389/fendo.2021.668073

Cited by 6 publications

(5 citation statements)

References 80 publications

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“…Metastasis and recurrence are common in patients with high-grade EC [ 2 ]. Plenty studies in recent years have revealed the versatile functions of circRNAs in the pathogenesis of EC [ 30 , 31 ]. Among them, the role of circWDR26 in the pathogenesis of EC is still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

“…The important roles of circRNAs in cancers are emerging [ 5 , 32 , 33 ], but more researches are still required to understand their roles and underlying mechanisms which regulate tumor progression. WDR26 was upregulated in multiple cancers to promote tumor progression [ 30 , 31 ]. Upregulated WDR26 may also lead to elevation of circWDR26.…”

Section: Discussionmentioning

confidence: 99%

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CircWDR26 regulates endometrial carcinoma progression via miR-212-3p-mediated typing genes MSH2

Lei

Cao

et al. 2022

Eur J Med Res

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Background Circular RNAs (circRNA) are important in mediating tumor progression, but their roles in endometrial carcinoma (EC) are not fully understood yet. Many circRNAs are dysregulated and may contribute to EC progression. The functions of circWDR26 in EC remain unknown. Methods The expression of circWDR26 in EC and adjacent normal tissues, and cell lines was determined by qPCR. The proliferation, apoptosis, migration, and invasion of EC cells was examined by CCK-8 assay, flow cytometry, wound healing assay and Transwell assay. The interaction between circWDR26, MSH2 and miR-212-3p was determined by luciferase assay. EC cells were inoculated into nude mice and tumor burden was determined by measuring tumor dimensions, size, and weight. The proliferative marker Ki67 in EC tissue was determined by immunohistochemistry. Results The expression of circWDR26 in EC tissues or cell lines was higher than in the normal tissue or endometrial epithelial cells. Downregulation of circWDR26 resulted in attenuated proliferation, increased apoptosis, reduced migration and invasion of EC cells. Mechanistically, circWDR26 targeted and suppressed the expression of miR-212-3p. We further found that MSH2 was the novel target of miR-212-3p and was upregulated by circWDR26 via inhibiting miR-212-3p. In vivo experiment demonstrated that circWDR26 was essential for EC tumor growth. Conclusion circWDR26 promoted EC progression by regulating miR-212-3p/MSH2 axis and provided novel insights into anti-cancer treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

CircWDR26 regulates endometrial carcinoma progression via miR-212-3p-mediated typing genes MSH2

Lei

Cao

et al. 2022

Eur J Med Res

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“…Circular RNAs (circRNAs), a subset of long non-coding RNAs (lncRNAs), are characterized by a covalently closed loop structure without a 5’-3’ polarity or a poly(A) tail, which increases stability and resistance to RNase R ( 8 , 9 ). In recent years, next-generation sequencing technology has accelerated the discovery of circRNAs, allowing investigation into their biological roles in gene regulation; for instance, circRNAs act as microRNA (miRNA) sponges to bind miRNAs in competitive endogenous RNA (ceRNA) networks ( 10 , 11 ). Emerging evidence suggests that circRNAs may contribute to disease development, including endometriosis ( 8 , 11 ).…”

Section: Introductionmentioning

confidence: 99%

“…In recent years, next-generation sequencing technology has accelerated the discovery of circRNAs, allowing investigation into their biological roles in gene regulation; for instance, circRNAs act as microRNA (miRNA) sponges to bind miRNAs in competitive endogenous RNA (ceRNA) networks ( 10 , 11 ). Emerging evidence suggests that circRNAs may contribute to disease development, including endometriosis ( 8 , 11 ). However, there are few studies on the function of circRNAs in CCs of patients with infertility along with endometriosis.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic analysis confirms differences in circular RNA expression profiles of cumulus cells between patients with ovarian and peritoneal endometriosis-associated infertility

Huang

2023

Front. Endocrinol.

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Endometriosis has a detrimental effect on oocyte quality, and ovarian endometriosis (OEM) and peritoneal endometriosis (PEM) may have different effects on female fertility. Therefore, we conducted a study to explore the circular RNA (circRNA) expression profiles of cumulus cells (CCs) in patients with OEM (n = 3), PEM (n = 3), and tubal factor infertility (TFI, n = 3) using high-throughput sequencing techniques and attempted to identify common and unique circRNAs in the OEM and PEM groups. The CIRCexplorer2 program was used to identify circRNAs. Seven candidate circRNAs were validated in 30 samples using quantitative real-time polymerase chain reaction (qRT-PCR). Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to annotate the function of circRNA-targeted genes, which were verified by sequencing results and constructed circRNA–miRNA–mRNA networks. A total of 11833 circRNAs were identified in nine samples. The numbers of differentially expressed circRNAs between the OEM and TFI groups, PEM and TFI groups, and OEM and PEM groups were 130, 71, and 191, respectively. After taking intersections, 11 circRNAs were considered common circRNAs in the OEM and PEM groups; 39 circRNAs in the OEM group and 17 circRNAs in the PEM group were identified as unique key circRNAs. During qRT-PCR validation, hsa_circ_0003638 was significantly upregulated in the PEM group compared to that in the OEM and TFI groups. Functional analysis of circRNA-targeted genes revealed that apoptosis, PI3K-AKT, and p53 signaling pathways were enriched in the PEM–TFI comparison groups, whereas the functions of target genes involved in the JAK–STAT and TGF-β signaling pathways were enriched in the PEM–OEM comparison groups. Our findings confirmed differences in circRNA expression profiles of CCs between patients with OEM and PEM infertility and provide new insights into the different effects of various endometriosis phenotypes on oocytes.

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“…And an increasing number of studies have found that circRNAs play an important role in the regulation of gene expression, the development of disease, and are therefore closely associated with physiological processes and various diseases [ 40 ]. In addition, studies have shown that circRNAs are expressed in normal endometrium, endometriosis, and endometrial cancer [ 41 ]. Taken together, these results suggest that circRNAs play an important biological regulatory role in the endometrium.…”

Section: Introductionmentioning

confidence: 99%

Identification and characterization of circRNAs in peri-implantation endometrium between Yorkshire and Erhualian pigs

Zhou¹,

Xu²,

Meng³

et al. 2023

BMC Genomics

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Background One of the most critical periods for the loss of pig embryos is the 12th day of gestation when implantation begins. Recent studies have shown that non-coding RNAs (ncRNAs) play important regulatory roles during pregnancy. Circular RNAs (circRNAs) are a kind of ubiquitously expressed ncRNAs that can directly regulate the binding proteins or regulate the expression of target genes by adsorbing micro RNAs (miRNA). Results We used the Illumina Novaseq6,000 technology to analyze the circRNA expression profile in the endometrium of three Erhualian (EH12) and three Yorkshire (YK12) pigs on day 12 of gestation. Overall, a total of 22,108 circRNAs were identified. Of these, 4051 circRNAs were specific to EH12 and 5889 circRNAs were specific to YK12, indicating a high level of breed specificity. Further analysis showed that there were 641 significant differentially expressed circRNAs (SDEcircRNAs) in EH12 compared with YK12 (FDR < 0.05). Functional enrichment of differential circRNA host genes revealed many pathways and genes associated with reproduction and regulation of embryo development. Network analysis of circRNA-miRNA interactions further supported the idea that circRNAs act as sponges for miRNAs to regulate gene expression. The prediction of differential circRNA binding proteins further explored the potential regulatory pathways of circRNAs. Analysis of SDEcircRNAs suggested a possible reason for the difference in embryo survival between the two breeds at the peri-implantation stage. Conclusions Together, these data suggest that circRNAs are abundantly expressed in the endometrium during the peri-implantation period in pigs and are important regulators of related genes. The results of this study will help to further understand the differences in molecular pathways between the two breeds during the critical implantation period of pregnancy, and will help to provide insight into the molecular mechanisms that contribute to the establishment of pregnancy and embryo loss in pigs.

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Current and Future Roles of Circular RNAs in Normal and Pathological Endometrium

Cited by 6 publications

References 80 publications

CircWDR26 regulates endometrial carcinoma progression via miR-212-3p-mediated typing genes MSH2

CircWDR26 regulates endometrial carcinoma progression via miR-212-3p-mediated typing genes MSH2

Bioinformatic analysis confirms differences in circular RNA expression profiles of cumulus cells between patients with ovarian and peritoneal endometriosis-associated infertility

Identification and characterization of circRNAs in peri-implantation endometrium between Yorkshire and Erhualian pigs

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