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Abstract：
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.
CONCLUSIONS: 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.
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.
CONCLUSIONS: 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.
摘要：
目的：皮肤皮肤黑色素瘤（SKCM）是最严重的，和所有皮肤癌的复杂疾病。这种癌症进展的分子机制尚不清楚。
方法：GEPIA在线数据库用于验证来自两个GEO数据集的差异表达基因。通过Kaplan-Meier方法计算预后价值。RT-qPCR验证了TUBB4A在SKCM细胞系中的表达，从人类蛋白质图谱获得SKCM和正常皮肤组织中TUBB4A的免疫组织化学。七个靶标预测数据库预测了潜在的微小RNA（miRNA），和上游长非编码RNA(lncRNA)通过starBase预测。使用两个在线分析位点UALCAN和starBase获得TUBB4A的共表达基因。这些共表达的基因通过富集分析进行，免疫浸润结果通过TIMER2在线数据库获得。应用受试者工作特征(ROC)曲线评价TUBB4A对SKCM和正常皮肤组的诊断价值。构建了有关TUBB4A的新列线图，以预测SKCM患者在1、3和5年的生存率。
结果：首先，我们发现DLL3和TUBB4A在皮肤黑色素瘤中的表达明显高于正常皮肤。随后，通过分析无进展间隔(PFI)，疾病特异性生存(DSS)，和无病生存率（DFS），只有TUBB4A是抑制胫骨皮肤黑素瘤进展的最有效基因。在基因本体论（GO）/京都基因和基因组百科全书（KEGG）分析中，TUBB4A可能通过调节线粒体功能和影响细胞代谢在皮肤黑素瘤的进展中发挥关键作用。可能与CD4+Th1细胞和NK细胞的免疫浸润有关。上游非编码RNA(ncRNA)通过SNHG16-hsa-let-7b-5p-TUBB4A轴发挥作用。
结论：结论：我们通过调节线粒体功能影响细胞代谢,阐明了SNHG16-hsa-let-7b-5p-TUBB4A轴在皮肤皮肤黑色素瘤进展中的调节作用.TUBB4A可能是皮肤黑素瘤的有前途的诊断生物标志物和治疗靶标。
方法：GEPIA在线数据库用于验证来自两个GEO数据集的差异表达基因。通过Kaplan-Meier方法计算预后价值。RT-qPCR验证了TUBB4A在SKCM细胞系中的表达，从人类蛋白质图谱获得SKCM和正常皮肤组织中TUBB4A的免疫组织化学。七个靶标预测数据库预测了潜在的微小RNA（miRNA），和上游长非编码RNA(lncRNA)通过starBase预测。使用两个在线分析位点UALCAN和starBase获得TUBB4A的共表达基因。这些共表达的基因通过富集分析进行，免疫浸润结果通过TIMER2在线数据库获得。应用受试者工作特征(ROC)曲线评价TUBB4A对SKCM和正常皮肤组的诊断价值。构建了有关TUBB4A的新列线图，以预测SKCM患者在1、3和5年的生存率。
结果：首先，我们发现DLL3和TUBB4A在皮肤黑色素瘤中的表达明显高于正常皮肤。随后，通过分析无进展间隔(PFI)，疾病特异性生存(DSS)，和无病生存率（DFS），只有TUBB4A是抑制胫骨皮肤黑素瘤进展的最有效基因。在基因本体论（GO）/京都基因和基因组百科全书（KEGG）分析中，TUBB4A可能通过调节线粒体功能和影响细胞代谢在皮肤黑素瘤的进展中发挥关键作用。可能与CD4+Th1细胞和NK细胞的免疫浸润有关。上游非编码RNA(ncRNA)通过SNHG16-hsa-let-7b-5p-TUBB4A轴发挥作用。
结论：结论：我们通过调节线粒体功能影响细胞代谢,阐明了SNHG16-hsa-let-7b-5p-TUBB4A轴在皮肤皮肤黑色素瘤进展中的调节作用.TUBB4A可能是皮肤黑素瘤的有前途的诊断生物标志物和治疗靶标。
