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

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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.

References

  • de Fraipont F et al (2019) Circular RNAs and RNA splice variants as biomarkers for prognosis and therapeutic response in the liquid biopsies of lung cancer patients. Front Genet 10:390

    Article  Google Scholar 

  • Del Vescovo V, Denti MA (2015) microRNA and lung cancer. Adv Exp Med Biol 889:153–177

    Article  Google Scholar 

  • Fujimoto J, Wistuba II (2014) Current concepts on the molecular pathology of non-small cell lung carcinoma. Semin Diagn Pathol 31(4):306–313

    Article  Google Scholar 

  • Hansen TB et al (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495(7441):384–388

    Article  CAS  Google Scholar 

  • Huang AC et al (2016) Bufalin inhibits gefitinib resistant NCI-H460 human lung cancer cell migration and invasion in vitro. J Ethnopharmacol 194:1043–1050

    Article  CAS  Google Scholar 

  • Lee S et al (2014) Cyto-/genotoxic effects of the ethanol extract of Chan Su, a traditional Chinese medicine, in human cancer cell lines. J Ethnopharmacol 152(2):372–376

    Article  Google Scholar 

  • Lemjabbar-Alaoui H et al (2015) Lung cancer: biology and treatment options. Biochim Biophys Acta 1856(2):189–210

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu F et al (2016) Bufalin enhances antitumor effect of paclitaxel on cervical tumorigenesis via inhibiting the integrin alpha2/beta5/FAK signaling pathway. Oncotarget 7(8):8896–8907

    Article  Google Scholar 

  • Liu T et al (2017) Bufalin inhibits cellular proliferation and cancer stem cell-like phenotypes via upregulation of MiR-203 in glioma. Cell Physiol Biochem 44(2):671–681

    Article  Google Scholar 

  • Low JL et al (2019) The evolving immuno-oncology landscape in advanced lung cancer: first-line treatment of non-small cell lung cancer. Ther Adv Med Oncol 11:1758835919870360

    Article  CAS  Google Scholar 

  • Martinez P et al (2014) Molecular targeted therapy for early-stage non-small-cell lung cancer: will it increase the cure rate? Lung Cancer 84(2):97–100

    Article  Google Scholar 

  • Miao Q et al (2013) Anticancer effects of bufalin on human hepatocellular carcinoma HepG2 cells: roles of apoptosis and autophagy. Int J Mol Sci 14(1):1370–1382

    Article  CAS  Google Scholar 

  • Naorem LD, Muthaiyan M, Venkatesan A (2019) Identification of dysregulated miRNAs in triple negative breast cancer: a meta-analysis approach. J Cell Physiol 234(7):11768–11779

    Article  CAS  Google Scholar 

  • Qi F et al (2011) Antitumor activity of extracts and compounds from the skin of the toad Bufo bufo gargarizans Cantor. Int Immunopharmacol 11(3):342–349

    Article  CAS  Google Scholar 

  • Shen S et al (2014) Bufalin induces the interplay between apoptosis and autophagy in glioma cells through endoplasmic reticulum stress. Int J Biol Sci 10(2):212–224

    Article  CAS  Google Scholar 

  • Shi J et al (2019) Overexpression of LINC00261 inhibits non-small cell lung cancer cells progression by interacting with miR-522-3p and suppressing Wnt signaling. J Cell Biochem 120(10):18378–18387

    Article  CAS  Google Scholar 

  • Shuai F, Wang B, Dong S (2018) miR-522-3p promotes tumorigenesis in human colorectal cancer via targeting bloom syndrome protein. Oncol Res 26(7):1113–1121

    Article  Google Scholar 

  • Wang H et al (2016) Bufalin suppresses hepatocellular carcinoma invasion and metastasis by targeting HIF-1alpha via the PI3K/AKT/mTOR pathway. Oncotarget 7(15):20193–20208

    Article  Google Scholar 

  • Wang L et al (2018) Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-beta-induced epithelial-mesenchymal transition and metastasis by controlling TIF1gamma in non-small cell lung cancer. Mol Cancer 17(1):140

    Article  Google Scholar 

  • Wang J et al (2019) Circular RNAs: a rising star in respiratory diseases. Respir Res 20(1):3

    Article  Google Scholar 

  • Yang L et al (2018) Hsa_circ_0046264 up-regulated BRCA2 to suppress lung cancer through targeting hsa-miR-1245. Respir Res 19(1):115

    Article  Google Scholar 

  • Yi Y et al (2019) Reconstruction and analysis of circRNAmiRNAmRNA network in the pathology of cervical cancer. Oncol Rep 41(4):2209–2225

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhao H, Zhang L (2018a) Identification of the tumorsuppressive function of circular RNA FOXO3 in nonsmall cell lung cancer through sponging miR155. Mol Med Rep 17(6):7692–7700

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang S et al (2018b) Microarray profile of circular RNAs identifies hsa_circ_0014130 as a new circular RNA biomarker in non-small cell lung cancer. Sci Rep 8(1):2878

    Article  Google Scholar 

  • Zhang JJ et al (2019) Bufalin suppresses the migration and invasion of prostate cancer cells through HOTAIR, the sponge of miR-520b. Acta Pharmacol Sin 40(9):1228–1236

    Article  Google Scholar 

  • Zhao L et al (2015) Bufalin inhibits TGF-beta-induced epithelial-to-mesenchymal transition and migration in human lung cancer A549 cells by downregulating TGF-beta receptors. Int J Mol Med 36(3):645–652

    Article  CAS  Google Scholar 

  • Zhu Z et al (2012) Bufalin induces lung cancer cell apoptosis via the inhibition of PI3K/Akt pathway. Int J Mol Sci 13(2):2025–2035

    Article  CAS  Google Scholar 

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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 43, 1229–1240 (2021). https://doi.org/10.1007/s10529-021-03081-6

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  • DOI: https://doi.org/10.1007/s10529-021-03081-6

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