Journal ID : CJOHNS-06-07-2022-11284
[This article belongs to Volume - 57, Issue - 06]

Title : Study on the effect and mechanisms of SIGLEC-15 on laryngeal squamous cell carcinoma

Abstract :

To investigate the effect of sialic acid combined with immunoglobulin-like lectin 15 (SIGLEC-15) on laryngeal squamous cell carcinoma (LSCC) and underlying mechanisms. The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE) and Gene Expression Profiling Interactive Analysis (GEPIA2) databases were used for bioinformatics analysis. Cell Counting Kit-8 (CCK8), flow cytometry, and Transwell method were used respectively to detect proliferation, apoptosis, cell cycle, metastasis and invasion behaviors of the cells. Gene chip method was used for detecting up-regulated and down-regulated genes and performing enrichment analysis of differential genes. Western Blotting (WB) and Quantitative Real-time PCR (qPCR) were used to detect the expressions of proteins. Tumor formation experiments in nude mice were used to detect the effect of SIGLEC-15 on the growth of transplanted tumors. Wilcoxon rank sum test, t-test and Log-rank test were used for statistical analysis. SIGLEC-15 was highly expressed in laryngeal squamous cell carcinoma and closely related to life in being. TU686SIGLEC-15-with low expression of SIGLEC-15 was constructed. Compared to TU686SIGLEC-15+, TU686SIGLEC-15-showed significantly reduced activities of proliferation (48 h: 1.32±0.23 vs. 2.56±0.37, t=6.59, P<0.05), migration (1 036.52±51.22 vs. 1 819.62±180.24, t=7.22, P<0.05) and invasion (469.21±112.25 vs. 961.45±102.03, t=7.85, P<0.05); early increased apoptosis ((23.27±1.12)% vs. (5.64±1.61)%, t=11.32, P<0.05); blocked cell cycle at G0/G1 ((59.32±3.65)% vs. (35.46±3.57)%, t=9.85, P<0.05); the knockdown of SIGLEC-15 resulted in up-regulation of 864 genes, down-regulation of 357 genes, with significant changes in molecules of cell cycle, apoptosis and JAK/STAT signal pathways, and the expressions of p-JAK2, p-STAT3, Caspase-3, Bad, Bcl-2, and Cyclin d1 proteins. Tumor formation experiments in nude mice showed that at 8 weeks after the tumors were implanted, the growth transplanted tumors of TU686 SIGLEC-15-cell group was slower than that of TU686 SIGLEC-15+cell group, with significant difference in the mean tumor weights between two groups ((0.382±0.054) g vs. (1.277±0.126) g, t=8.44, P<0.05), while the expression of SIGLEC-15 was lower in the transplanted tumors of SIGLEC-15 knockdown group compared to control group, with significant difference(11.29±2.17 vs. 36.25±7.56, t=9.28, P<0.05). SIGLEC-15 is highly expressed in LSCC and can promote the progression of LSCC through the JAK2-STAT3 pathway

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