Abstract
Background
Pheochromocytoma (PCC) is a catecholamine-producing and neuroendocrine tumor with the 5-year overall survival of advanced stage PCC lower than 40%. Increasing evidence has shown that aberrant expression of microRNAs (miRNAs) plays important roles in the development and chemotherapy resistance of cancers including PCC.
Objective
The tumor-suppressive function of miR-184 has been identified in several types of cancers. The aim of this study is to explore the function and the underlying mechanism of miR-184 in the chemo-resistance of PCC.
Results
miR-184 expression was significantly lower in doxorubicin (Dox)-resistant pheochromocytoma-12 (PC-12) cells and PCC patients. Consistently, in vitro analysis showed that overexpression of miR-184 obviously improved the sensitivity of PC-12/Dox cells, while knockdown of miR-184 sensitised PC-12/Dox cells to chemotherapeutics. To further understand the possible functional mechanism of miR184 in the chemo-resistance of PCC, the targets of miR-184 were predicted. The results of miRDB database suggested A disintegrin and metalloproteinase 22 (ADAM22) carrying the potential complementary binding sites of miR-184 within its 3′-untranslated region (UTR). Further experiments confirmed that miR-184 bound the 3′-UTR of ADAM22 mRNA and down-regulated the expression of ADAM22 in PC-12/Dox cells. Moreover, ADAM22 was overexpressed in Dox-resistant PC-12 cells and PCC patients. Additionally, overexpression of ADAM22 attenuated miR-184-mediated chemo-sensitivity of PC-12/Dox cells.
Conclusion
miR-184 played a role in the chemo-sensitivity of PC-12/Dox cells at least partially via negatively regulating ADAM22. These results suggested miR-184 as a possible novel target to attenuate the chemo-resistance of PCC.
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Acknowledgements
This work was supported by the Medical Science Research Project of Hebei Province in 2020 (20200306).
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Zhao, N., Su, N., Wang, G. et al. microRNA-184 enhances the sensitivity of pheochromocytoma-12 cells to doxorubicin by targeting ADAM22. Mol. Cell. Toxicol. 17, 123–132 (2021). https://doi.org/10.1007/s13273-021-00116-x
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DOI: https://doi.org/10.1007/s13273-021-00116-x