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Long Noncoding RNA ACTA2-AS1 Inhibits Cell Growth and Facilitates Apoptosis in Gastric Cancer by Binding with miR-6720-5p to Regulate ESRRB

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Abstract

Gastric cancer (GC) is a common malignant tumor, posing a great threat to human’s health and life. Previous studies have suggested aberrant expression of long non-coding RNAs (lncRNAs) in GC. This study elucidated the effects of lncRNA ACTA2-AS1 on the biological characteristics of GC. Gene expression in stomach adenocarcinoma (STAD) samples compared with normal tissues and the correlation between gene expression and prognosis of STAD patients were analyzed using bioinformatic tools. Gene expression at protein and mRNA levels in GC and normal cells was tested by western blotting and RT-qPCR. The subcellular localization of ACTA2-AS1 in AGS and HGC27 cells was identified by nuclear-cytoplasmic fractionation and FISH assay. EdU, CCK-8, flow cytometry analysis, TUNEL staining assays were conducted to evaluate the role of ACTA2-AS1 and ESRRB on GC cellular behaviors. The binding relationship among ACTA2-AS1, miR-6720-5p and ESRRB was verified by RNA pulldown, luciferase reporter assay and RIP assay. LncRNA ACTA2-AS1 was underexpressed in GC tissues and cell lines. ACTA2-AS1 elevation suppressed GC cell proliferation and induced apoptosis. Mechanistically, ACTA2-AS1 directly bound to miR-6720-5p and subsequently promoted the expression of target gene ESRRB in GC cells. Furthermore, ESRRB knockdown reversed the influence of ACTA2-AS1 overexpression on GC proliferation and apoptosis. ACTA2-AS1 plays an antioncogenic role in GC via binding with miR-6720-5p to regulate ESRRB expression.

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Data Availability

The datasets used during the current study are available from the corresponding author on reasonable request.

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Funding

The work was supported by Hubei Provincial Department of Education Fund (Grant No. B2020108).

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Author notes

  1. Zuchao Hu, Zhen Chen and Wei Jiang authors contributed equally to the work.

Authors and Affiliations

  1. The Second Ward of Surgery, Sinophram Hanjiang Hospital, Shiyan, Hubei, China

    Zuchao Hu

  2. Department of Emergency, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, No. 26 Shengli Street, Jiang’an District, Wuhan, Hubei, China

    Zhen Chen, Wei Jiang & Fen Ai

  3. Department of Thyroid and Breast, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, Shiyan, Hubei, China

    Dazheng Fang, Shouguo Yao, Ming Luo, Lei Wang, Zhengfu Sun, Wei Wang, Xin Wang & Haibo Mao

  4. The Second Ward of Internal Medicine, Sinophram Hanjiang Hospital, Shiyan, Hubei, China

    Ping Peng

  5. Department of Gastrointestinal Surgery, Sinopharm Dongfeng General Hospital, Hubei University of Medicine, No. 16, Daling Road, Zhangwan District, Shiyan, Hubei, China

    Peihua Zhou

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  1. Zuchao Hu
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Contributions

ZH, ZC and WJ conceived and designed the experiments. ZH, ZC, WJ, DF, PP, SY, ML, LW, ZS, WW, XW, HM, FA, and PZ carried out the experiments. ZH, ZC,WJ, FA, and PZ analyzed the data. ZH, ZC,WJ, FA, and PZ drafted the manuscript. All authors agreed to be accountable for all aspects of the work. All authors have read and approved the final manuscript.

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Correspondence to Fen Ai or Peihua Zhou.

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All authors contributed equally to the work.

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Hu, Z., Chen, Z., Jiang, W. et al. Long Noncoding RNA ACTA2-AS1 Inhibits Cell Growth and Facilitates Apoptosis in Gastric Cancer by Binding with miR-6720-5p to Regulate ESRRB. Biochem Genet 61, 2672–2690 (2023). https://doi.org/10.1007/s10528-023-10399-5

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