Aims

This study aimed to explore the role of Isoliquiritigenin (ISL) in the proliferation and invasion of melanoma cells and to investigate the mechanism of action of the compound.

Main methods

The functional roles of ISL in melanoma cells were determined by CCK8 assay, colony formation assay, flow cytometry and wound healing assay. The antitumor activity of ISL was assessed in vivo in a mouse xenograft model using A2058 cells. Quantitative real-time PCR analysis (RT-qPCR) and western blot assays were used to evaluate the gene and protein expression in cell lines or tumor tissue samples. Bioinformatic analysis, luciferase reporter assay, and gene set enrichment analysis (GSEA) were performed to confirm the mechanism of ISL effect on cell growth and metastasis of melanoma.

Key findings

ISL suppressed proliferation and migration of melanoma cells via downregulation of miR-27a expression. The inhibitory effect of ISL on growth and metastasis of melanoma cells was reversed by ectopic expression of miR-27a. Bioinformatic analysis showed that miR-27a targets POU class 2 homeobox 3 (POU2F3); this result was verified by the luciferase reporter assay and by a decrease in the expression of POU2F3 by miR-27a intervention. GSEA demonstrated that POU2F3 is associated with the c-MYC/p53 signaling pathway and metastasis. POU2F3 knockdown reversed the inhibitory effect of ISL on the growth and metastasis of melanoma. Additionally, POU2F3 was found to be downregulated in melanoma tissue samples and was negatively correlated with miR-27a.

Significance

ISL inhibits proliferation and metastasis of melanoma via the miR-27a/POU2F3/c-MYC/p53 axis; these results may provide a new thought for the treatment of melanoma.

中文翻译：

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膳食类黄酮异甘草素诱导的细胞凋亡和抑制黑色素瘤细胞转移：一个在体外和体内研究

目的

这项研究旨在探讨异黄体生成素（ISL）在黑素瘤细胞增殖和侵袭中的作用，并研究该化合物的作用机理。

主要方法

通过CCK8测定，集落形成测定，流式细胞术和伤口愈合测定来确定ISL在黑素瘤细胞中的功能作用。使用A2058细胞在小鼠异种移植模型中体内评估了ISL的抗肿瘤活性。实时定量PCR分析（RT-qPCR）和蛋白质印迹分析用于评估细胞系或肿瘤组织样品中的基因和蛋白质表达。进行了生物信息学分析，荧光素酶报告基因分析和基因组富集分析（GSEA），以确认ISL对黑素瘤细胞生长和转移的影响机制。

主要发现

ISL通过下调miR-27a表达来抑制黑素瘤细胞的增殖和迁移。miR-27a的异位表达逆转了ISL对黑素瘤细胞生长和转移的抑制作用。生物信息学分析表明，miR-27a靶向POU 2类同源盒3（POU2F3）；萤光素酶报告基因测定法和miR-27a干预降低了POU2F3的表达，证实了这一结果。GSEA证明POU2F3与c-MYC / p53信号通路和转移有关。POU2F3敲低逆转了ISL对黑素瘤生长和转移的抑制作用。另外，发现POU2F3在黑色素瘤组织样品中下调，并且与miR-27a负相关。

意义

ISL通过miR-27a / POU2F3 / c-MYC / p53轴抑制黑素瘤的增殖和转移；这些结果可能为黑色素瘤的治疗提供新思路。