Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Pan Y

PROVIDER: S-EPMC9233859 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature

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Publications

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

Pan Yuliang Y Zhu Yuxing Y Zhang Jun J Jin Long L Cao Peiguo P

Journal of translational medicine 20220625 1

<h4>Background</h4>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.<h4>Methods</h4>Colony formation assay, flow cytometry analysis and transwell assay were implemented to de ...[more]

PMID: 35752837

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Project description:BackgroundHuman gastric cancer is a serious disease with high mortality rate all over the world. The one of difficulties in effective therapy of gastric cancer is metastasis. It has been reported that lncRNAs and miRNAs are involved in cancer metastasis. So, exploration of new molecular mechanism underlying gastric cancer metastasis involving in network of lncRNAs/miRNAs/effector proteins is important and meaningful for guiding the treatment of gastric cancer.MethodsMTT assay, flow cytometric analysis and colony formation assay were performed to evaluate AGS or MKN-45 cell proliferation, cycle distribution and colony formation, and RT-qPCR was used to examine the expressive abundances of EDIL3, XIST and miR-137. EDIL3 and epithelial-mesenchymal transition (EMT) related proteins were detected by western blot and migration and invasion were measured by transwell analysis. Meanwhile, Dual-luciferase reporter gene assay was used to confirm XIST binding to miR-137, and miR-137 binding to EDIL3. AGS cells were used to establish the xenograft tumor model to verify the role of EDIL3 in tumorigenesis in nude mice.ResultsExpression levels of EDIL3 was increased in gastric cancer tissues and cell lines. Downregulation of EDIL3 or XIST and overexpression of miR-137 inhibited proliferation, migration, invasion and EMT in AGS and MKN-45 cells. XIST could specifically bind to miR-137, and EDIL3 was a target gene of miR-137. Moreover, TGF-β1 stimulated XIST expression, inhibited miR-137 expression and induced migration, invasion and EMT. We also found that overexpression of EDIL3 elevated levels of TGF-β1 and induced migration, invasion and EMT, which were reversed by TGF-β1 inhibition. EDIL3 knockdown suppressed migration, invasion and EMT, which were reversed by XIST. Overexpression of miR-137 inhibited proliferation, migration, invasion and EMT, which were reversed by EDIL3 overexpression.ConclusionsEDIL3 regulates gastric cancer cell migration, invasion and EMT, which is involved in the regulation of TGF-β1/XIST/miR-137 feedback loop, and EDIL3 knockdown inhibits tumor growth in nude mice. These findings indicate that the EDIL3 mediated molecular feedback loop may be developed as drug targets for the gastric carcinoma treatment.

Dataset Information

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

Background

Methods

Results

Conclusion

Publications

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

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