Kun Zhang1, Chunfang Yu2, Ruoxi Tian3, Wancong Zhang1, Shijie Tang4, Guiying Wang5. 1. Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, CN, China. 2. Department of Nursing, Second Affiliated Hospital of Guilin Medical University, Guilin, Guangxi, CN, China. 3. School of Basic Medicine, Tianjin Medical University, Tianjin, CN, China. 4. Department of Plastic Surgery and Burn Center, Second Affiliated Hospital, Shantou University Medical College, Shantou, Guangdong, CN, China. sjtang3@stu.edu.cn. 5. Department of General Surgery, Third Hospital of Hebei Medical University, Shijiazhuang, Hbei, CN, China. wangguiying@hebmu.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Meilin Wu; Jun Li; Kurt A Engleka; Bo Zhou; Min Min Lu; Joshua B Plotkin; Jonathan A Epstein Journal: J Clin Invest Date: 2008-06 Impact factor: 14.808
Authors: Joseph B Mascarenhas; Erica L Littlejohn; Rebecca J Wolsky; Kacey P Young; Maria Nelson; Ravi Salgia; Deborah Lang Journal: Pigment Cell Melanoma Res Date: 2010-01-22 Impact factor: 4.693
Authors: O Hamid; C Robert; A Daud; F S Hodi; W J Hwu; R Kefford; J D Wolchok; P Hersey; R Joseph; J S Weber; R Dronca; T C Mitchell; A Patnaik; H M Zarour; A M Joshua; Q Zhao; E Jensen; S Ahsan; N Ibrahim; A Ribas Journal: Ann Oncol Date: 2019-04-01 Impact factor: 32.976