Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, CN, China.
Department of Nursing, Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, CN, China.
Mol Biol Rep. 2022 Oct;49(10):9137-9145. doi: 10.1007/s11033-022-07706-5. Epub 2022 Sep 4.
The PAX3 (paired box gene 3) gene is highly expressed in several cancer types. However, its underlying mechanism of action in skin cutaneous melanoma (SKCM) remains unknown.
In this study, we used the GEPIA database and western blotting to analyze the expression of PAX3. We performed the Kaplan-Meier survival analysis to evaluate the prognostic value of PAX3 in SKCM. Next, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to evaluate the function of PAX3-related co-expressed genes. Additionally, the function and potential mechanism of action of PAX3 in SKCM were studied through functional experiments. Western blotting was used to detect the changes in the levels of epithelial-mesenchymal transition (EMT)-related and MET (c-MET tyrosine kinase) proteins following PAX3 knockdown. Finally, we assessed the correlation between PAX3 expression and the infiltration of CD4/CD8 T cells using the TISIDB database.
We found that PAX3 was overexpressed in the SKCM tissues and that these levels were indicative of a poor prognosis of SKCM. The KEGG pathway enrichment analysis showed that PAX3-related co-expressed genes were mainly associated with the oncogenic pathways. Knocking down PAX3 significantly inhibited the proliferation, invasion, and migration of SK-MEL-28 cells. The PAX3 expression was related significantly to the immune infiltration level of CD4/CD8 T cells.
Our findings demonstrated that PAX3 knockdown could reverse the EMT of tumor cells, inhibit the growth, and progression of SKCM cells. Therefore, PAX3 may have implications as a potential therapeutic target and promising prognostic biomarker for SKCM.
PAX3（配对盒基因 3）基因在多种癌症类型中高度表达。然而，其在皮肤黑色素瘤（SKCM）中的作用机制尚不清楚。
本研究利用 GEPIA 数据库和 Western blot 分析 PAX3 的表达。通过 Kaplan-Meier 生存分析评估 PAX3 在 SKCM 中的预后价值。接下来，进行京都基因与基因组百科全书（KEGG）通路富集分析，以评估 PAX3 相关共表达基因的功能。此外，通过功能实验研究 PAX3 在 SKCM 中的功能和潜在作用机制。Western blot 检测 PAX3 敲低后上皮-间充质转化（EMT）相关和 MET（c-MET 酪氨酸激酶）蛋白水平的变化。最后，利用 TISIDB 数据库评估 PAX3 表达与 CD4/CD8 T 细胞浸润的相关性。
我们发现 PAX3 在 SKCM 组织中过表达，且其水平与 SKCM 的不良预后相关。KEGG 通路富集分析显示，PAX3 相关共表达基因主要与致癌途径相关。敲低 PAX3 可显著抑制 SK-MEL-28 细胞的增殖、侵袭和迁移。PAX3 的表达与 CD4/CD8 T 细胞的免疫浸润水平显著相关。
我们的研究结果表明，PAX3 敲低可逆转肿瘤细胞的 EMT，抑制 SKCM 细胞的生长和进展。因此，PAX3 可能作为 SKCM 的潜在治疗靶点和有前途的预后生物标志物具有重要意义。
