Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B.
Integration Analysis of m6A Related Genes in Skin Cutaneous Melanoma and the Biological Function Research of the SPRR1B.
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皮肤黑色素瘤m6A相关基因整合分析及SPRR1B生物学功能研究
DOI：
10.3389/fonc.2021.729045
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发表时间：
2021
影响因子：
4.7
通讯作者：
Zhou J
中科院分区：
文献类型：
--
作者：
Shi S;Fan Z;Liu Y;Huang C;Zhou J
黑色素瘤因其发病率高、患病率不断上升而逐渐进入公众视野，严重威胁人类的生命健康。最近，N6-甲基腺嘌呤（m6A）修饰已被越来越多地证实在肿瘤发生发展中具有潜在作用。本研究的目的是通过生物信息学和传统实验，从分子、细胞和临床水平探讨m6a相关调节因子在黑色素瘤疾病发生发展中的作用和功能。我们通过 GEO、GTEx、TCGA 数据库筛选并验证 m6A 调节子中的差异表达基因 (DEG)。通过构建PPI、GO富集、KEGG富集、GSEA富集、免疫浸润分析等生物信息方法，完善DEGs涉及的生物学过程和信号通路。然后，我们通过细胞侵袭、迁移、浸润和组织芯片来探索关键基因SPRR1B的生物学功能。筛选出m6A调控因子基因中差异表达的IGF2BP3基因。富集分析结果显着富集了皮肤屏障、表皮分化、细胞骨架、淋巴细胞迁移等通路的生物学过程和途径，为肿瘤免疫和肿瘤转移指明了方向。发现肿瘤免疫相关基因YTHDC1、YTHDC2和ALKBH5。敲SPRR1B减少组的侵袭能力、迁移能力明显降低。列线图预测模型显示 SPRR1B 增加，表示预后较差。为此，我们探讨了 m6A 调节因子与黑色素瘤进展之间的关系。同时发现转移前SPRR1B表达异常上调会导致黑色素瘤预后不良。 SPRR1B促进人黑色素瘤细胞的增殖、侵袭和迁移。
Melanoma has gradually entered the public view because of its high morbidity and rising prevalence rate, which is a serious threat to human life and health. Recently, N6-methyladenine (m6A) modification has been increasingly confirmed as a potential role in the development of tumogenesis. The purpose of this study is to explore the role and function of m6a-related regulators in the development of melanoma disease at the molecular, cellular and clinical levels through bioinformatics and traditional experiments. We screened and validated differential expression genes (DEGs) in m6A regulators via the GEO, GTEx, TCGA database. The biological processes and signaling pathway involved by DEGs were improved by constructing bioinformational methods such as PPI, GO enrichment, KEGG enrichment, GSEA enrichment, and immune infiltration analysis. And then, we explored the biological function of the key gene, SPRR1B, through cell invasion, migration, infiltration, and tissue chips. The gene IGF2BP3 which was differentially expressed in m6A regulatory factor gene was screened. The results of the enrichment analysis are significantly enriched in the biological processes and pathways of the skin barrier, epidermal differentiation, cytoskeleton, lymphocyte migration and other pathways, pointing to the direction of tumor immunity and tumor metastasis. Tumor immune-related genes YTHDC1, YTHDC2 and ALKBH5 were found. Knock SPRR1B reduction group had a significantly lower invasive ability, the ability to migrate. Nomogram prediction model shows that SPRR1B increased, expressing a worse prognosis. For this purpose, the relationship between m6A regulatory factor and melanoma progression was explored. At the same time, it was found that the abnormal up-regulated expression of SPRR1B before metastasis would lead to poor prognosis of melanoma. SPRR1B promotes the proliferation, invasion and migration of human melanoma cells.
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