journal contribution
posted on 2023-03-31, 02:42 authored by Jian Zhang, Ying-Qin Li, Rui Guo, Ya-Qin Wang, Pan-Pan Zhang, Xin-Ran Tang, Xin Wen, Xiao-Hong Hong, Yuan Lei, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Jun Ma, Na Liu Supplementary Figures S1-S8: -Figure S1. The SHISA3 promoter is hypermethylated in NPC. Figure S2. The SHISA3 promoter is hypermethylated in NPC cell lines. Figure S3. SHISA3 is hypermethylated in 18 primary solid tumors. Figure S4. Correlations between SHISA3 promoter methylation and mRNA expression in primary solid tumors. Figure S5. SHISA3 has little effect on NPC cell proliferation in vitro. Figure S6. SHISA3 stabilizes SGSM1 by impeding TRIM21-mediated deubiquitination. Figure S7. The effects of SHISA3 overexpression on nasopharyngeal carcinoma aggressiveness in vivo. Figure S8. SHISA3 has little effect on the canonical Wnt signaling pathway.
Funding
National Natural Science Foundation of China
Natural Science Foundation of Guangdong Province
History
ARTICLE ABSTRACT
Altered DNA methylation is a key feature of cancer, and aberrant methylation is important in nasopharyngeal carcinoma (NPC) development. However, the methylation mechanisms underlying metastasis of NPC remain unclear. Analyzing data from public databases and conducting our own experiments, we report here that promoter hypermethylation of SHISA3 is common and contributes to the downregulation of this gene in many types of tumors, including NPC. SHISA3 suppressed NPC cell invasion and metastasis in vitro and in vivo by impeding the E3 ubiquitin ligase tripartite motif containing 21 (TRIM21)–mediated ubiquitination and degradation small G protein signaling modulator 1 (SGSM1) and by inhibiting the MAPK pathway activation. Silencing SGSM1 abrogated the inhibitory effect of SHISA3 on NPC cell migration and invasion. This newly identified SHISA3–TRIM21–SGSM1 axis could be a novel therapeutic target in NPC.
These findings highlight the mechanism by which a newly identified tumor suppressor SHISA3 suppresses invasion and metastasis of nasopharyngeal carcinoma.
