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CircBLNK regulates tumor proliferation and apoptosis by miR-578/ING5 axis in non-small cell lung cancer

Abstract

Background

Non-small cell lung cancer (NSCLC) is one of most threatening malignancies with a high morbidity and mortality that threaten human health and life.

Objective

This study aimed to investigate the role of circBLNK in NSCLC and reveal the regulation mechanism of circBLNK in NSCLC. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to determine the levels of circBLNK, miR-578 and inhibitor of growth 5 (ING5) mRNA. Cell proliferation activity was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-ethynyl-2’-deoxyuridine (EdU) staining and colony formation assays. Flow cytometry was carried out to examine cell cycle and cell apoptosis. The dual-luciferase reporter assay was used to validate the interaction between miR-578 and circBLNK or ING5. Xenograft tumor experiment was performed to uncover the function of circBLNK in vivo.

Results

CircBLNK was notably down-regulated in NSCLC tissues and cells. Overexpression of circBLNK suppressed the proliferation and accelerated the apoptosis of NSCLC cells in vitro. CircBLNK targeted miR-578, and circBLNK exerted its biological function in NSCLC cells through sponging miR-578. ING5 was verified as a target of miR-578, and circBLNK increased the abundance of ING5 through targeting miR-578 in NSCLC cells. ING5 interference could partly reverse the biological effects of NSCLC cells mediated by circBLNK overexpression. CircBLNK overexpression repressed NSCLC tumor growth in vivo.

Conclusion

CircBLNK functioned as a tumor suppressor in NSCLC to suppress the proliferation and cell cycle and promote cell apoptosis of NSCLC cells through miR-578/ING5 axis.

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Authors and Affiliations

Authors

Contributions

All authors have been involved in the management of the patient and in the conception of the manuscript. The specific authors’ contribution is listed below. PL: Methodology, formal analysis and investigation, writing-original draft. LZ: Formal analysis and investigation, conceptualization. ZL: Formal analysis and investigation, resources. YL: Methodology, analysis and interpretation. SY: Formal analysis and investigation, resources. YZ: Methodology, resources. YX: Data collection, writing—review and editing.

Corresponding author

Correspondence to Yong Xie.

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Conflict of interest

Ping Li declares that she has no financial conflicts of interest. Liuyi Zou declares that he has no financial conflicts of interest. Zuojun Luo declares that he has no financial conflicts of interest. Yuhua Lu declares that she has no financial conflicts of interest. Shuang Yu declares that she has no financial conflicts of interest. Yujun Zhu declares that he has no financial conflicts of interest. Yong Xie declares that he has no financial conflicts of interest.

Ethics approval and consent to participate

Written informed consents were obtained from all participants and this study was permitted by the Ethics Committee of Yichun People’s Hospital & The Affiliated Yichun Hospital of Nanchang University.

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Li, P., Zou, L., Luo, Z. et al. CircBLNK regulates tumor proliferation and apoptosis by miR-578/ING5 axis in non-small cell lung cancer. Mol. Cell. Toxicol. (2022). https://doi.org/10.1007/s13273-022-00274-6

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  • DOI: https://doi.org/10.1007/s13273-022-00274-6

Keywords

  • Non-small cell lung cancer
  • circBLNK
  • miR-578
  • ING5
  • Proliferation
  • Apoptosis