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姜黄素通过 miR-222-3p/SOX10/Notch 轴抑制黑色素瘤的生长和转移。

Curcumin Inhibits the Growth and Metastasis of Melanoma via miR-222-3p/SOX10/Notch Axis.

机构信息

Department of Oncology, The Third Xiangya Hospital, Central South University, Changsha, 410013 Hunan, China.

出版信息

Dis Markers. 2022 May 9;2022:3129781. doi: 10.1155/2022/3129781. eCollection 2022.

Abstract

BACKGROUND

The aim of this study was to investigate the effect of curcumin on melanoma and its mechanism.

METHODS

Curcumin (0, 0.125, 0.25, or 0.5 mg/ml) was utilized to treat A375 and HT144 cell lines. The MTT analysis was used to confirm the proliferation ability. Wound healing and transwell analysis showed the migration and invasion ability. Immunofluorescence assay was used to demonstrate the effect of curcumin on SOX10 expression. Multiple bioinformatic analysis to confirm the SOX10 associated miRNA. The correlation of miR-222-3p and SOX10 was detected by Luciferase reporter assays. qRT-PCR showed the miR-222-3p level. Western blot analyzed the expression of SOX10, Notch1, and HES1 in melanoma cell treated with or without miR-222-3p inhibitor.

RESULTS

Curcumin could inhibit the proliferation, migration, and invasion of melanoma cells. Furthermore, curcumin repress the expression of SOX10, Notch1, and HES-1, and increase the expression of miR-222-3p. And the miR-222-3p could directly target to SOX10 mRNA to inhibit its expression. In addition, inhibition of miR-222-3p expression reversed the inhibitory effect of curcumin the growth of melanoma cells.

CONCLUSION

Curcumin enhances the miR-222-3p level to reduce SOX10 expression, and ultimately inactivates the Notch pathway in repressing melanoma proliferation, migration, and invasion.

摘要

背景

本研究旨在探讨姜黄素对黑色素瘤的作用及其机制。

方法

用姜黄素(0、0.125、0.25 或 0.5mg/ml)处理 A375 和 HT144 细胞系。MTT 分析用于确认增殖能力。划痕愈合和 Transwell 分析显示迁移和侵袭能力。免疫荧光分析用于证明姜黄素对 SOX10 表达的影响。多个生物信息学分析以确认与 SOX10 相关的 miRNA。通过荧光素酶报告实验检测 miR-222-3p 与 SOX10 的相关性。qRT-PCR 显示 miR-222-3p 水平。Western blot 分析经或未经 miR-222-3p 抑制剂处理的黑色素瘤细胞中 SOX10、Notch1 和 HES1 的表达。

结果

姜黄素可抑制黑色素瘤细胞的增殖、迁移和侵袭。此外,姜黄素抑制 SOX10、Notch1 和 HES-1 的表达,增加 miR-222-3p 的表达。miR-222-3p 可直接靶向 SOX10 mRNA 抑制其表达。此外,抑制 miR-222-3p 的表达逆转了姜黄素对黑色素瘤细胞生长的抑制作用。

结论

姜黄素通过提高 miR-222-3p 水平降低 SOX10 表达,最终通过抑制 Notch 通路抑制黑色素瘤细胞的增殖、迁移和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b6f4/9110126/e331f7c60e20/DM2022-3129781.001.jpg

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