Bufalin suppresses the migration and invasion of prostate cancer cells through HOTAIR, the sponge of miR-520b

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Abstract

Bufalin, the major active component of the traditional Chinese medicine ChanSu obtained from the skin and parotid venom glands of toads, has long been known as an anticancer agent. Recent studies show that microRNAs (miRs) are involved in the anticancer activities of bufalin, while long non-coding RNAs (lncRNAs) are known to interact with miRNAs to regulate various biological functions. In this paper, we investigated the possible network related to the antimetastatic effect of bufalin in prostate cancer (PCa) cells. We demonstrated that bufalin (0.05−10 µM) dose-dependently suppressed the proliferation of prostate cancer DU145 and PC3 cells with IC50 values of 0.89 and 1.28 µM, respectively. Furthermore, bufalin treatment significantly suppressed the cell migration and invasion. To explore the role of lncRNAs in the antimetastatic activity of bufalin, we used an lncRNA microarray and found that HOX transcript antisense RNA (HOTAIR) was the most markedly downregulated lncRNA in bufalin-treated PCa cells. Overexpression of HOTAIR counteracted the suppressing effects of bufalin on DU145 and PC3 cells. We then predicted and verified that HOTAIR upregulated FGFR1 expression by sponging miR-520b in PCa cells. In 40 patients with PCa bone metastasis, we used in situ hybridization or immunohistochemical assay to assess the HOTAIR and FGFR1 expression, which revealed that both HOTAIR and FGFR1 expression were significantly higher in bone metastasis tissues than in the primary PCa tissues. In addition, the level of serum HOTAIR was positively associated with the levels of serum bone metabolic markers (CTx, OST, B-ALP and PINP) and may serve as a reasonable biomarker for PCa bone metastasis. Taken together, this is the first study revealing that HOTAIR promotes PCa bone metastasis, and bufalin may be a promising candidate for the treatment of this disease.

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (No 81503396), the Shanghai Science and Technology Committee (No. 17411950300), the National Key Research Project of Science and Technology Ministry (No. 2016YFC0106204), the Shanghai Senior Integrative Chinese and Western Medicine Talents Program (ZY(2018-2020)-RCPY-2017, Pujiang Talent project (No. 17PJ1407600), and Talent project of the Sixth People`s Hospital of Shanghai (No. ynlc201603).

Author information

YY and HYH designed the research. XHZ and YZ performed the research. ANH finished the ISH and ICH assays. BZQ contributed analytic tools. YGW collected the samples and performed the pathology experiments. YZ followed-up the cases. ZS polished the English translation. JJZ analyzed the data and wrote the paper.

Correspondence to Hai-yan Hu or Yang Yao.

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The authors declare no competing interests.

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Zhang, J., Zhou, X., Zhou, Y. et al. Bufalin suppresses the migration and invasion of prostate cancer cells through HOTAIR, the sponge of miR-520b. Acta Pharmacol Sin 40, 1228–1236 (2019) doi:10.1038/s41401-019-0234-8

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Keywords

  • bufalin
  • traditional Chinese medicine; prostate cancer
  • bone metastasis
  • lncRNA
  • HOTAIR
  • miR-520b
  • FGFR1

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