环状 TNFRSF21，一种新鉴定的环状 RNA，通过调节 miR-1227-MAPK13/ATF2 轴促进子宫内膜癌的发病机制。

circTNFRSF21, a newly identified circular RNA promotes endometrial carcinoma pathogenesis through regulating miR-1227-MAPK13/ATF2 axis.

机构信息

Department of Obstetrics and Gynecology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing, China.

出版信息

Aging (Albany NY). 2020 Apr 16;12(8):6774-6792. doi: 10.18632/aging.103037.

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.

背景

环状 RNA 是一种具有调控基因表达潜力的非编码 RNA，与疾病进展有关。然而，环状 RNA 在子宫内膜癌（EC）中的作用在很大程度上尚不清楚。

结果

在这项研究中，我们发现 circTNFRSF21 在 EC 细胞和肿瘤组织中高度表达。体外和体内结果表明，circTNFRSF21 与 EC 细胞的生长增加和裸鼠 EC 异种移植物的形成有关。在机制上，我们表明 circTNFRSF21 作为 EC 细胞中 miR-1227 的海绵，以挽救 MAPK13/ATF2 信号通路活性。

结论

我们的研究表明，在 EC 中，circTNFRSF21 通过下调 miR-1227 的表达并激活 MAPK13/ATF2 信号通路来促进 EC 的形成。这些发现为 circTNFRSF21-miR-1227-MAPK13/ATF2 轴作为 EC 治疗的有前途的靶点提供了有力证据。

方法

qRT-PCR 用于检测 EC 患者和 EC 细胞系中的 circTNFRSF21 表达。细胞生长、细胞集落形成、细胞凋亡、细胞周期进程和体内肿瘤形成测定用于评估 circTNFRSF21 在 EC 中的作用。Western blot、荧光素酶测定、RNA 下拉、siRNA 敲低和 CRISPR 基因敲除测定用于研究 circTNFRSF21 调节 EC 形成的机制。