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LncRNA GATA3-AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR-361/ARRB2 axis

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A Correction to this article was published on 20 October 2022

A Correction to this article was published on 26 August 2022

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Abstract

Endometrial carcinoma (EC) is a kind of fatal female malignancy. lncRNA GATA3-AS1 has been identified as an oncogene in various cancers. However, the functions and mechanisms of GATA3-AS1 in EC remain to be explored. Human EC tissues and four EC cell lines were used. Western blotting and quantitative real-time PCR (qRT-PCR) were used to evaluate the expression of GATA3-AS1, miR-361, and ARRB2. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to validate the interaction among GATA3-AS1, miR-361, and ARRB2. Flow cytometry, colony formation assay, scratch assay, and transwell assay were used to examine the cell apoptosis, proliferation, migration, and invasion of EC cells, respectively. In vivo tumor growth was monitored in nude mice. GATA3-AS1 and ARRB2 were upregulated while miR-361 was downregulated in human EC tissues and EC cells. GATA3-AS1 knockdown constrained cell proliferation, invasion, migration, and EMT while promoting the apoptosis of EC cells by upregulating miR-361. GATA3-AS1 negatively regulated miR-361 expression. ARRB2 was the direct target of miR-361 and could activate the Src/Akt pathway. In vivo, GATA3-AS1 knockdown suppressed tumor progression by upregulating the miR-361 expression. lncRNA GATA3-AS1 promoted EC invasion and migration by the miR-361/ARRB2 axis, which indicated that GATA3-AS1 might be a promising therapeutic option for advanced EC progression.

Key messages

  • GATA3-AS1 knockdown suppressed EC proliferation, invasion, and migration.

  • GATA3-AS1 directly inhibited miR-361 as a ceRNA.

  • MiR-361 knockdown reversed the tumor suppressive effect caused by GATA3-AS1 knockdown.

  • MiR-361 bound to ARRB2 directly and suppressed its expression.

  • The GATA3-AS1/miR-361/ARRB2 axis regulated EC cell proliferation, invasion, and migration.

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All data generated or analyzed during this study are included in this published article.

Change history

Abbreviations

EC:

Endometrial carcinoma

qRT-PCR:

Quantitative real-time PCR

RIP:

RNA immunoprecipitation

LncRNA:

Long non-coding RNA

HESC:

Human endometrial stromal cells

shRNA:

Short hairpin RNA

MOI:

Multiplicity of infection

PET:

Polyethylene terephthalate

IHC:

Immunohistochemistry

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

Funding

This work was supported by DENG Gao-pi, Guangdong Provincial Traditional Chinese Medicine Heritage Studio (No.20195) and Sanming Project of Medicine in Shenzhen (No.SZZYSM202106003).

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Authors and Affiliations

  1. Department of Gynecology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, 510080, Guangdong Province, People’s Republic of China

    Yu-xi Liu, Shuo Yuan, Xiao-jing Liu, Yan-xi Huang, Pin Qiu, Jie Gao & Gao-pi Deng

  2. Guangzhou University of Chinese Medicine, Guangzhou, 510080, Guangdong Province, People’s Republic of China

    Yu-xi Liu

  3. Lingnan Medical Research Center of Guangzhou University of Chinese Medicine, Guangzhou, 510080, Guangdong Province, People’s Republic of China

    Yu-xi Liu

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  1. Yu-xi Liu
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Contributions

Yu-xi Liu: writing—original draft preparation, supervision, conceptualization. Shuo Yuan: software, investigation. Xiao-jing Liu: data curation, software. Yan-xi Huang: visualization. Pin Qiu: data curation. Jie Gao: methodology, validation, writing—reviewing and editing. Gao-pi Deng: methodology, validation, writing—reviewing and editing.

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Correspondence to Jie Gao or Gao-pi Deng.

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Ethics approval and consent to participate

The tissues were harvested from the First Affiliated Hospital of Guangzhou University of Chinese Medicine during 2017–2018. The human and animal experimentations in this study were approved by the ethics committee of the First Affiliated Hospital of Guangzhou University of Chinese Medicine. All the related patients have signed informed consent.

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The authors declare no competing interests.

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Jie Gao and Gao-pi Deng are co-corresponding authors.

The original online version of this article was revised: Affiliation 4 is deleted as it is not affiliated to the last Author.

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Liu, Yx., Yuan, S., Liu, Xj. et al. LncRNA GATA3-AS1 promoted invasion and migration in human endometrial carcinoma by regulating the miR-361/ARRB2 axis. J Mol Med 100, 1271–1286 (2022). https://doi.org/10.1007/s00109-022-02222-2

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