GATA2-AS1 与 GATA2 之间的反馈环通过招募 DDX3X 促进结直肠癌细胞增殖、侵袭、上皮-间充质转化和干性。

A feedback loop between GATA2-AS1 and GATA2 promotes colorectal cancer cell proliferation, invasion, epithelial-mesenchymal transition and stemness via recruiting DDX3X.

机构信息

Department of Oncology, the Third Xiangya Hospital of Central South University, No.138, Tongzipo Road, Yuelu District, Changsha, 410013, Hunan, China.

出版信息

J Transl Med. 2022 Jun 25;20(1):287. doi: 10.1186/s12967-022-03483-8.

BACKGROUND

Colorectal cancer (CRC) is a common malignant tumor with a high risk of metastasis. Long non-coding RNAs (lncRNAs) have been reported to be implicated in cancer progression via regulating its nearby gene. Herein, we investigated the function of GATA binding protein 2 (GATA2) and lncRNA GATA2 antisense RNA 1 (GATA2-AS1) in CRC and the mechanism underlying their interaction.

METHODS

Colony formation assay, flow cytometry analysis and transwell assay were implemented to detect cell proliferation, apoptosis and invasion. Western blot analysis and sphere formation assay were conducted to assess epithelial-mesenchymal transition (EMT) and cancer stemness of CRC cells. RNA pull down, RNA-binding protein immunoprecipitation (RIP), chromatin immunoprecipitation (ChIP) and luciferase reporter assays were implemented to investigate the regulatory mechanism between GATA2-AS1 and GATA2.

RESULTS

GATA2-AS1 and GATA2 were highly expressed in CRC cells. Knockdown of GATA2-AS1 and GATA2 impeded CRC cell proliferation, invasion, EMT and cancer stemness, and induced cell apoptosis. GATA2-AS1 expression was positively correlated with GATA2. GATA2-AS1 recruited DEAD-box helicase 3 X-linked (DDX3X) to stabilize GATA2 mRNA. GATA2 combined with GATA2-AS1 promoter to enhance GATA2-AS1 expression.

CONCLUSION

Our study confirmed that a feedback loop between GATA2-AS1 and GATA2 promotes CRC progression, which might offer novel targets for CRC treatment.

背景

结直肠癌（CRC）是一种常见的恶性肿瘤，具有较高的转移风险。长链非编码 RNA（lncRNA）已被报道通过调节其附近基因参与癌症进展。在此，我们研究了 GATA 结合蛋白 2（GATA2）和 lncRNA GATA2 反义 RNA 1（GATA2-AS1）在 CRC 中的功能及其相互作用的机制。

方法

采用集落形成实验、流式细胞术分析和 Transwell 实验检测细胞增殖、凋亡和侵袭；Western blot 分析和球体形成实验评估 CRC 细胞的上皮-间充质转化（EMT）和癌症干性；采用 RNA 下拉、RNA 结合蛋白免疫沉淀（RIP）、染色质免疫沉淀（ChIP）和荧光素酶报告基因实验研究 GATA2-AS1 和 GATA2 之间的调控机制。

结果

GATA2-AS1 和 GATA2 在 CRC 细胞中高表达。敲低 GATA2-AS1 和 GATA2 抑制 CRC 细胞增殖、侵袭、EMT 和癌症干性，并诱导细胞凋亡。GATA2-AS1 的表达与 GATA2 呈正相关。GATA2-AS1 招募 X 连锁 DEAD 盒解旋酶 3（DDX3X）稳定 GATA2 mRNA。GATA2 结合 GATA2-AS1 启动子增强 GATA2-AS1 表达。