Abstract
Objectives Abnormal expression of trefoil factor 3 (TFF3) in breast, stomach, and colon tumors may be related to the occurrence of tumors, suggesting its role in angiogenesis. In this study, the aim was to explore the role of TFF3 in thyroid cancer. Methods TFF3 expression analysis was performed via GEPIA and RT-PCR. To explore the effects of TFF3 on thyroid cancer cell motility, cell function assays were performed. Furthermore, GSEA pathway analysis and western blot were used to explore the mechanism by which TFF3 represses the progression of thyroid cancer cells. Results Here, we showed that low expression level of TFF3 in thyroid cancer is related to thyroid cancer nodal metastasis. The patients with low TFF3 expression showed worse disease-free survival than those with high level of TFF3. Underexpressed TFF3 increased cell motility and inhibited cell apoptosis. We found that the levels of IL-6, p-JAK2/JAK2, and pSTAT3/STAT3 were inhibited in the pcDNA-TFF3 group compared to the pcDNA-NC group and these factors were upregulated in the si-TFF3 group compared to the si-NC group in BCPAP and TPC-1 cells. Conclusion TFF3 inhibits thyroid cancer cell progression related to IL-6/JAK/STAT3 signaling pathway.
Highlights
The Kaplan–Meier overall survival curve for patients with thyroid cancer classified according to relative trefoil factor 3 (TFF3) expression was analyzed by the Gene Expression Profiling Interactive Analysis (GEPIA) website [16]. e database used by UALCAN and GEPIA was obtained from e Cancer Genome Atlas (TCGA, https://cancergenome.nih.gov/) databases
The expression and prognosis value of TFF3 were analyzed by UALCAN and GEPIA websites based on the TCGA database. e results of Figure 1(a) show that TFF3 expression was significantly downregulated in thyroid cancer tissues in comparison to the normal tissues. en, we observed high level of TFF3 in normal tissues and low expression of TFF3 in the tissues of thyroid cancer stage 1, stage 2, stage 3, and stage 4 (P < 0.01; Figure 1(b))
In order to evaluate the level of TFF3 in cancerous and normal thyroid cells, its mRNA and protein levels were tested in 5 cancerous cell lines, FTC133, BCPAP, TPC-1, 8505C, and SW579, and a normal thyroid cell line Nthy-ori 3-1 using RT-PCR and western blot
Summary
Abnormal expression of trefoil factor 3 (TFF3) in breast, stomach, and colon tumors may be related to the occurrence of tumors, suggesting its role in angiogenesis. The aim was to explore the role of TFF3 in thyroid cancer. TFF3 expression analysis was performed via GEPIA and RT-PCR. To explore the effects of TFF3 on thyroid cancer cell motility, cell function assays were performed. GSEA pathway analysis and western blot were used to explore the mechanism by which TFF3 represses the progression of thyroid cancer cells. We showed that low expression level of TFF3 in thyroid cancer is related to thyroid cancer nodal metastasis. We found that the levels of IL-6, p-JAK2/JAK2, and pSTAT3/STAT3 were inhibited in the pcDNA-TFF3 group compared to the pcDNA-NC group and these factors were upregulated in the si-TFF3 group compared to the si-NC group in BCPAP and TPC-1 cells. TFF3 inhibits thyroid cancer cell progression related to IL-6/JAK/STAT3 signaling pathway
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