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The tumor suppressor function of hsa_circ_0006282 in gastric cancer through PTEN/AKT pathway

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Abstract

Background

Circular RNAs (circRNAs) play key roles in carcinogenesis. However, the roles of circRNAs in gastric cancer are largely unknown. The aim of this study is to study the possible roles of hsa_circ_0006282 in gastric cancer.

Methods

The hsa_circ_0006282 levels in gastric cancer cell lines, 85 gastritis tissues, and 103 paired gastric cancer tissues and non-tumor tissues were first detected by quantitative real-time reverse transcription-polymerase chain reaction. RNA interference and hsa_circ_0006282 expression plasmid were further used to manipulate hsa_circ_0006282 expression in gastric cancer. Finally, biological effects of hsa_circ_0006282 were analyzed by real-time cell analysis, flow cytometry, Transwell, cell cloning assay and Western blot analysis.

Results

Hsa_circ_0006282 was down expressed in gastric cancer cells, gastritis tissues, and gastric cancer tissues. The abilities of cell proliferation, cell migration and resistance to apoptosis were enhanced after hsa_circ_0006282 was downregulated, while overexpression of hsa_circ_0006282 got opposite results. Besides, Western blot showed that the levels of protein kinase B (AKT) and cyclin-dependent kinase 2 (CDK2) were significantly increased and decreased after knockdown and up-regulation of hsa_circ_0006282, respectively, while phosphatase and tensin homolog deleted on chromosome ten (PTEN) was significantly opposite regulated. Finally, hsa_circ_0006282 promoted the expression of PTEN by sponging hsa-miR-136-5p.

Conclusion

By regulating the PTEN/AKT signaling pathway through competitively binding with hsa-miR-136-5p, hsa_circ_0006282 suppresses the growth of gastric cancer.

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Data availability

The datasets are available from the corresponding author.

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Acknowledgements

The authors thank for the technical support by the Core Facilities, Ningbo University School of Medicine.

Funding

It was supported by The National Natural Science Foundation of China (81772279), Ningbo Municipal Bureau of Science and Technology (No. 2021Z133, No. 2022Z130 and No. 2017C110019), Ningbo Nature Fund Project (No.2021J253), Zhejiang Province Public Welfare Technology Application Research Project of China (No. LGF22H160039), and the K. C. Wong Magna Fund in Ningbo University.

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Author notes

  1. Zhe Li and Yi Xie have equal contribution.

Authors and Affiliations

  1. Department of Gastroenterology, The Affiliated Hospital of Medical School, Ningbo University, Ningbo, 315020, China

    Zhe Li & Junming Guo

  2. Department of Biochemistry and Molecular Biology, and Zhejiang Key Laboratory of Pathophysiology, Medical School of Ningbo University, Ningbo, 315211, China

    Yi Xie, Bingxiu Xiao & Junming Guo

  3. Institute of Digestive Diseases of Ningbo University, Ningbo, 315020, China

    Junming Guo

Authors
  1. Zhe Li
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  2. Yi Xie
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  3. Bingxiu Xiao
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  4. Junming Guo
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Contributions

ZL, YX, and BX collected clinical information; ZL, YX, and JG wrote the manuscript; JG designed the study. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Junming Guo.

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No author has any conflict of interest.

Ethics approval

The authors adhered to institutional ethical standards. The Human Research Ethics Committee at Ningbo University (approval number 20100303) approved this study.

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Li, Z., Xie, Y., Xiao, B. et al. The tumor suppressor function of hsa_circ_0006282 in gastric cancer through PTEN/AKT pathway. Int J Clin Oncol 27, 1562–1569 (2022). https://doi.org/10.1007/s10147-022-02210-z

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  • DOI: https://doi.org/10.1007/s10147-022-02210-z

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