Abstract
A previous report suggested that the expression of ten-eleven translocation (TET) proteins is abnormal in certain cancers. Quercetin has been demonstrated as anti-cancer role in cancer development. In order to explore the inhibitory effect and mechanism of quercetin on uveal melanoma cells, the expression of TET proteins was analyzed in the present study. Our results suggest that the expression of TET1 was increased following treatment with quercetin in OCM-1, SK-MEL-1, and B16 cells. In addition, quercetin treatment induced apoptosis and inhibited migration and invasion. To further investigate the association of the expression of TET1 with cell growth, apoptosis, migration, and invasion, cell lines in which TET1 was knocked-down or overexpressed were constructed. The results showed that the increased expression of TET1-induced apoptosis, increased 5-hydroxymethylcytosine (5 hmC). and inhibited invasion. Our bioinformatics studies indicated that TET1 is a target gene of microRNA-17 (miR-17) Our results showed that inhibition of the expression of miR-17 resulted in increased TET1 expression in OCM-1 cells. Furthermore, our results indicated that quercetin treatment increased TET1 expression and inhibited melanoma growth in nude mice. Taken together, our results suggest that quercetin can regulate cell proliferation and apoptosis through TET1 via miR-17 in melanoma cells.
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The authors thank Changchun University of Chinese Medicine for providing the cell lines.
Funding
This work was supported by the Jilin Health Commission Program under Grant 2020J05S, the Fundamental Research Funds for the Central Universities under Grant 2019JCKT-70, the Jilin Education Department Program under Grant JJKH20200950KJ, and the Jilin Scientific and Technological Development Program under Grant 20190103071JH, 202002006JC and 20220505033ZP.
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YG and DW designed the experiments and wrote the manuscript. YG, CL, TX and RH performed cell experiments and gene expression analyses. DD and YF contributed reagents and materials. CL carried out animal experiments. CL and QX analyzed the data and prepared figures. All authors reviewed the manuscript.
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All protocols of animal experiments performed in this study were approved by the Animal Care and Use Committee of Jilin University in accordance with the Guidelines on Animal Care and Use of Animals in Research (Grant No. SY20191210). The animal experiment design follows the 3R rule. Each nude mouse was anesthetized by intraperitoneal injection of 50 mg/kg sodium pentobarbital and euthanized by cervical dislocation. All procedures were carried out under ARRIVE guidelines (https://arriveguidelines.org). All authors agreed to the contents of this manuscript.
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Gao, Y., Li, C., Xue, T. et al. Quercetin Mediated TET1 Expression Through MicroRNA-17 Induced Cell Apoptosis in Melanoma Cells. Biochem Genet 61, 762–777 (2023). https://doi.org/10.1007/s10528-022-10286-5
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DOI: https://doi.org/10.1007/s10528-022-10286-5