Abstract
Late-stage melanoma is refractory to current therapies. MicroRNAs (miRNAs) can modulate many physiological and pathological processes of melanoma. Studies have demonstrated that miR-137 acts as a tumor suppressor by inhibiting the proliferation of melanoma cells through targeting multiple mRNAs. The glyoxalase system member glyoxalase 1 (GLO1) is the principal scavenging enzyme of methylglyoxal (MG), a toxic byproduct of glycolysis. Using 35S in vivo/vitro labelling analysis for dynamic proteomics (SiLAD), we found that miR-137 downregulated the expression of GLO1 in melanoma cells. Bioinformatics analysis predicted that GLO1 is a direct target of miR-137. This was validated by dual luciferase reporter assay. Quantitative RT-PCR (qRT-PCR) and western blot analysis indicated that miR-137 could decrease endogenous GLO1 expression. Furthermore, siRNA targeting of GLO1 mimicked inhibition of melanoma cell proliferation caused by miR-137 overexpression. Re-expression of GLO1 was able to restore miR-137-mediated suppression of melanoma cell proliferation. Therefore, these results suggest that miR-137 inhibits the proliferation of melanoma cells by targeting GLO1.
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Acknowledgements
This work was supported by the Special Funds for Major State Basic Research of China (2011CB915504), Coalition for National Science Funding (31171371 (2011–2015) to Dacheng He), and the German Cancer Aid (Melanoma Research Network) to Dr. Stefan B. Eichmüller.
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Lv, N., Hao, S., Luo, C. et al. miR-137 inhibits melanoma cell proliferation through downregulation of GLO1. Sci. China Life Sci. 61, 541–549 (2018). https://doi.org/10.1007/s11427-017-9138-9
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DOI: https://doi.org/10.1007/s11427-017-9138-9