Abstract
Background: Circular RNA is a type of non-coding RNA with great potential in regulating gene expression and associated with disease progression. However, the role of circular RNA in endometrial carcinoma (EC) remains largely unknown.Results: In this study, we found that circTNFRSF21 was highly expressed in EC cells and tumor tissues. In vitro and in vivo results showed that circTNFRSF21 was linked to increased EC cell growth and EC xenografts formation in nude mice. Mechanically, we showed that circTNFRSF21 acts as a sponge of miR-1227 in EC cells to rescue MAPK13/ATF2 signaling pathway activity.Conclusions: Our studies suggested that in the EC, circTNFRSF21 promotes EC formation through downregulating miR-1227 expression and activating MAPK13/ATF2 signaling pathway. These findings provide strong evidence that circTNFRSF21-miR-1227-MAPK13/ATF2 axis is a promising target for EC treatment.Methods: qRT-PCR was used to detect circTNFRSF21expression in EC patients and EC cell lines. Cell growth, cell colony formation, cell apoptosis, cell cycle progression, and in vivo tumor formation assays were used to evaluate the roles of circTNFRSF21 in EC. Western blot, luciferase assay, RNA pull-down, siRNA knockdown, and CRISPR gene knock out assays were applied to study the mechanisms through which circTNFRSF21 regulates EC formation.
Highlights
Endometrial carcinoma (EC) is the most common gynecologic malignancy of the female reproductive system [1]
By studying the circular RNA database, we found that this circular RNA was back spliced by exon 2 and 3 of TNFRSF21 transcripts (Figure 1A)
Both Ago2 and EIF4A3 greatly precipitated circTNFRSF21 compared with IgG control, and EIF4A3 has a better affinity with circTNFRSF21 than Ago2 (Figure 1D, **P
Summary
Endometrial carcinoma (EC) is the most common gynecologic malignancy of the female reproductive system [1]. Most type I EC patients exhibit low grade adenocarcinomas with relatively good survival rates [10, 11]. Circular RNA is a type of non-coding RNA with great potential in regulating gene expression and associated with disease progression. Results: In this study, we found that circTNFRSF21 was highly expressed in EC cells and tumor tissues. We showed that circTNFRSF21 acts as a sponge of miR-1227 in EC cells to rescue MAPK13/ATF2 signaling pathway activity. Conclusions: Our studies suggested that in the EC, circTNFRSF21 promotes EC formation through downregulating miR-1227 expression and activating MAPK13/ATF2 signaling pathway. These findings provide strong evidence that circTNFRSF21-miR-1227-MAPK13/ATF2 axis is a promising target for EC treatment. Luciferase assay, RNA pull-down, siRNA knockdown, and CRISPR gene knock out assays were applied to study the mechanisms through which circTNFRSF21 regulates EC formation
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