肿瘤细胞治疗研究
英文原题：Dysregulation of SNHG16(lncRNA)-Hsa-Let-7b-5p(miRNA)-TUBB4A (mRNA) Pathway Fuels Progression of Skin Cutaneous Melanoma.
我们阐明了SNHG16-hsa-let-7b-5p-TUBB4A轴通过调节线粒体功能影响细胞代谢，从而在皮肤黑色素瘤进展中发挥调控作用。
目的：皮肤黑色素瘤（SKCM）是所有皮肤癌中最严重、最复杂的疾病，其进展的分子机制尚未得到充分理解。 方法：使用GEPIA在线数据库验证两个GEO数据集中的差异表达基因。采用Kaplan-Meier法计算预后价值。通过RT-qPCR验证SKCM细胞系中TUBB4A表达；从人类蛋白质图谱获取SKCM及正常皮肤组织的TUBB4A免疫组化结果。七个靶点预测数据库用于预测潜在微RNA（miRNA），starBase用于预测上游长链非编码RNA（lncRNA）。使用UALCAN和starBase两个在线分析网站获取TUBB4A共表达基因，并对其开展富集分析；通过TIMER2在线数据库获得免疫浸润结果。采用受试者工作特征（ROC）曲线评估TUBB4A在SKCM与正常皮肤组间的诊断价值，并构建TUBB4A列线图预测SKCM患者1、3和5年生存率。 结果：研究首先发现，DLL3和TUBB4A在皮肤黑色素瘤中的表达显著高于正常皮肤。随后通过分析无进展间期（PFI）、疾病特异性生存期（DSS）和无病生存期（DFS），发现TUBB4A是抑制皮肤黑色素瘤进展潜力最大的基因。基因本体（GO）/京都基因与基因组百科全书（KEGG）分析显示，TUBB4A可能通过调节线粒体功能和影响细胞代谢，在皮肤黑色素瘤进展中发挥关键作用，并可能与CD4⁺ Th1细胞及NK细胞浸润有关。上游非编码RNA（ncRNA）通过SNHG16-hsa-let-7b-5p-TUBB4A轴发挥作用。 结论：本研究阐明了SNHG16-hsa-let-7b-5p-TUBB4A轴通过调节线粒体功能、影响细胞代谢，从而参与皮肤黑色素瘤进展的调控作用。TUBB4A可能成为皮肤黑色素瘤有前景的诊断生物标志物和治疗靶点。
OBJECTIVE: Skin cutaneous melanoma(SKCM) is the most severe, and complex disease of all skin cancers. The molecular mechanisms of this cancer progression are not well understood. METHODS: GEPIA online database was used to validate the differentially expressed genes from two GEO datasets. The prognostic value was calculated by the Kaplan-Meier method. RT-qPCR verified the expression of TUBB4A in SKCM cell line, and the immunohistochemistry of TUBB4A in SKCM and normal skin tissues were gained from Human Protein Atlas. Seven target prediction databases predicted potential microRNAs(miRNAs), and upstream long non-coding RNAs(lncRNAs) were predicted by starBase. The co-expressed gene of TUBB4A was obtained using the two online analysis sites UALCAN and starBase. These co-expressed genes were performed by enrichment analysis, and immune infiltration result was obtained by the TIMER2 online database. The receiver operating characteristic( ROC) curve was applied to evaluate the diagnostic value of TUBB4A in the SKCM and normal skin group. A new nomogram about TUBB4A was constructed to forecast the survival rate of SKCM patients at 1, 3, and 5 years. RESULTS: Firstly, we found that DLL3 and TUBB4A were significantly higher expressed in skin cutaneous melanoma than normal skin. Subsequently, by analyzing progress-free interval(PFI), diseasespecific survival(DSS), and disease-free survival(DFS), only TUBB4A was the most potent gene for inhibiting shin cutaneous melanoma progression. In gene ontology(GO)/ kyoto encyclopedia of genes and genomes(KEGG) analysis, TUBB4A may play a key role in the progression of skin cutaneous melanoma by regulating mitochondrial function and affecting cellular metabolism, possibly related to the immune infiltration of CD4+Th1 cells and NK cells. The upstream non-coding RNA(ncRNA) acts through the SNHG16-hsa-let-7b-5p-TUBB4A axis. CONCLUSION: In conclusion, we elucidated the regulatory role of the SNHG16-hsa-let-7b-5p-TUBB4A axis in the progression of skin cutaneous melanoma by modulating mitochondrial function to affect cellular metabolism. TUBB4A may be a promising diagnostic biomarker and therapeutic target for cutaneous skin melanoma.
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