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Published on: June 7, 2019
Quercetin Mediated TET1 Expression Through MicroRNA-17 Induced Cell Apoptosis in Melanoma Cells
Yongjian Gao1, Chengshun Li2, Tianyi Xue2
1Department of Gastrointestinal Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, China.
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.
Insights
Quercetin increases ten-eleven translocation 1 (TET1) expression, promoting apoptosis and inhibiting growth in uveal melanoma cells. This occurs via the microRNA-17 (miR-17) pathway, offering a potential therapeutic strategy for melanoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Abnormal expression of ten-eleven translocation (TET) proteins is implicated in various cancers.
- Quercetin exhibits anti-cancer properties and is investigated for its effects on cancer development.
Purpose of the Study:
- To explore the inhibitory effects and underlying mechanisms of quercetin on uveal melanoma cells.
- To analyze the role of TET proteins, specifically TET1, in quercetin's anti-cancer activity.
Main Methods:
- Analysis of TET1 expression in melanoma cell lines (OCM-1, SK-MEL-1, B16) after quercetin treatment.
- Construction of cell lines with altered TET1 expression (knock-down and overexpression) to assess functional impacts.
- Bioinformatic analysis to identify regulatory relationships between TET1 and microRNA-17 (miR-17).
- In vivo studies using nude mice to evaluate quercetin's effect on melanoma growth.
Main Results:
- Quercetin treatment upregulated TET1 expression in melanoma cells.
- Quercetin induced apoptosis, inhibited migration and invasion, and increased 5-hydroxymethylcytosine (5hmC) levels.
- Increased TET1 expression promoted apoptosis, enhanced 5hmC, and suppressed invasion.
- TET1 was identified as a target gene of miR-17, and miR-17 inhibition led to increased TET1 expression.
- Quercetin administration inhibited melanoma growth in vivo.
Conclusions:
- Quercetin exerts anti-cancer effects in uveal melanoma by upregulating TET1 expression.
- The quercetin-TET1-miR-17 axis regulates melanoma cell proliferation and apoptosis.
- Quercetin represents a potential therapeutic agent for melanoma, acting through the modulation of TET1 and miR-17.
