miR-412抑制SOX6对黑色素瘤细胞的增殖及侵袭力影响的研究

Upregulation of miR-412 promotes melanoma proliferation and invasion by suppressing SOX6 expression

目的检测微小RNA(miR)在人黑色素瘤中的表达情况,研究miR-412通过抑制性别确定区Y框转录因子6(SOX6)的表达影响黑色素瘤细胞增殖及侵袭能力的变化。方法癌症基因组图谱(TCGA)数据库分析发现miR-412在黑色素瘤中异常表达,为研究其表达与肿瘤的相关性,采用Transwell小室,非锚定独立生长实验分析miR-412对黑色素瘤细胞增殖及侵袭能力的影响。软件预测SOX6可能为其靶向基因,采用荧光素酶报告分析及Western blot实验检测SOX6与miR-412的靶向调节情况。结果TCGA数据库分析黑色素瘤组织中miR-412表达水平高于正常对照组,表达越高,生存时间越短。Transwell小室,非锚定独立生长实验显示miR-412过表达后促进细胞增殖及侵袭能力,而下调miR-412后抑制黑色素瘤细胞增殖及侵袭能力;通过靶点预测miR-412结合SOX6基因3’-非翻译区(UTR),导致SOX6蛋白因miR-412表达增高而下调;同时在miR-412下调的细胞中抑制SOX6表达可恢复黑色素瘤细胞的增殖及侵袭能力。结论miR-412过表达后促进黑色素瘤细胞增殖及侵袭能力,反之则抑制黑色素瘤细胞增殖及侵袭能力。miR-412通过靶向调控SOX6影响黑色素瘤细胞增殖及侵袭,提示miR-412在黑色素瘤的发病过程中起重要作用,是潜在的治疗靶点。

Objective To assess the expression of miR-412 in human melanoma and investigate how miR-412 modulates melanoma cell proliferation and invasive capacity by inhibiting SRY-Box Transcription Factor 6,(SOX6)expression.Methods Analysis of the TCGA(The Cancer Genome Atlas)database identified aberrant miR-412 expression in melanoma.To explore its relevance to tumorigenesis,we conducted Transwell chamber and non-adherent independent growth assays to examine the effects of miR-412 on melanoma cell proliferation and invasion.Software predictions highlighted SOX6 as a potential target gene.We performed luciferase reporter assays and Western blot experiments to elucidate the regulatory interactions between SOX6 and miR-412.Results TCGA database analysis revealed significantly elevated miR-412 expression levels in melanoma tissues compared to the normal control group.Moreover,higher miR-412 expression correlated with shorter survival times.Functional assays using Transwell chambers and non-adherent independent growth assays demonstrated that overexpressing miR-412 enhanced cell proliferation and invasive capabilities.Conversely,reducing miR-412 expression restrained these attributes in melanoma cells.Target prediction analysis indicated that miR-412 binds to the 3’-UTR region of SOX6,resulting in decreased SOX6 protein levels due to increased miR-412 expression.Intriguingly,inhibiting SOX6 expression concurrently amplified the proliferation and invasive potential of melanoma cells,which was initially dampened by miR-412 downregulation.Conclusions Elevated miR-412 expression augments melanoma cell proliferation and invasive capabilities,while its suppression diminishes these traits.Through its targeted regulation of SOX6,miR-412 exerts a significant influence on melanoma cell proliferation and invasion.These findings underscore the pivotal role of miR-412 in melanoma pathogenesis and underscore its potential as a promising therapeutic target.