Bufalin inhibits the malignant development of non-small cell lung cancer by mediating the circ_0046264/miR-522-3p axis

Abstract

Background

Bufalin is an active component of the traditional Chinese medicine “Chan Su” and is reported to play anti-tumor roles in cancer development, but its functional mechanism is largely unclear. This study intends to explore a potential action mode of bufalin in NSCLC.

Materials and methods

The malignant properties of NSCLC, including cell viability, proliferation, adhesion capacity, migration and invasion, were monitored by cell counting kit-8 (CCK-8), adhesion assay and transwell assay, respectively. The expression of circ_0046264 and miR-522-3p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of proliferation- and migration-related markers was examined by western blot. The putative relationship between circ_0046264 and miR-522-3p was verified by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Animal experiments in nude mice were performed to investigate the role of bufalin in vivo.

Results

Bufalin treatment inhibited cell viability, colony formation, cell adhesion capacity, migration and invasion in NSCLC cells. Bufalin facilitated the expression of circ_0046264, and circ_0046264 overexpression also inhibited NSCLC cell viability, colony formation, cell adhesion capacity, migration and invasion. Besides, circ_0046264 knockdown partially counteracted the effects of bufalin. Further, miR-522-3p was identified as a target of circ_0046264, and its deficiency reversed the effects of circ_0046264 knockdown to suppress malignant activities of NSCLC cells. In addition, bufalin restrained the tumor growth and development in vivo via enhancing the expression of circ_0046264.

Conclusion

Bufalin played an anti-tumor role in NSCLC by modulating the circ_0046264/miR-522-3p pathway, which might be a potential functional mechanism of bufalin in NSCLC.

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Availability of data and materials

The analyzed data sets generated during the present study are available from the corresponding author on reasonable request.

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Funding

This work was supported by the General program of Natural Science Foundation of Xinjiang Uygur Autonomous Region (Grant No. 2018D01C194).

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Contributions

Conceptualization and Methodology: ZY and HQ; Formal analysis and Data curation: KW and XX; Validation and Investigation: JJ and KW; Writing—original draft preparation and Writing—review and editing: JJ, ZY and HQ; Approval of final manuscript: all authors.

Corresponding author

Correspondence to Xiaoyi Xin.

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The authors declare that they have no competing interests.

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The present study was approved by the ethical review committee of the First Affiliated Hospital of Xinjiang Medical University.

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Jin, J., Yao, Z., Qin, H. et al. Bufalin inhibits the malignant development of non-small cell lung cancer by mediating the circ_0046264/miR-522-3p axis. Biotechnol Lett (2021). https://doi.org/10.1007/s10529-021-03081-6

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Keywords

  • Bufalin
  • circ_0046264
  • miR-522-3p
  • NSCLC