The Expression of Transcription Factors is Different in Papillary Thyroid Cancer Cells during TNF - α induced EMT.

The Expression of Transcription Factors is Different in Papillary Thyroid Cancer Cells during TNF - α induced EMT.
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DOI:
10.7150/jca.53349
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发表时间:
2021
期刊:
影响因子:
3.9
通讯作者:
Kuang J
Kuang J
中科院分区:
医学3区
文献类型:
--
作者:
Lv N;Liu F;Cheng L;Liu F;Kuang J

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促炎因子肿瘤坏死因子-α(TNF-α)是肿瘤微环境和自身免疫性疾病中重要的炎症介质,在许多实体瘤和肿瘤微环境中高度表达,显示出促肿瘤发生的作用。然而,肿瘤坏死因子-α增加甲状腺癌侵袭的分子机制仍不完全清楚。为探讨肿瘤坏死因子-α(TNF-α)是否在甲状腺乳头状癌(PTC)上皮间质转化(EMT)过程中起关键作用,我们用TNF-α诱导不同的PTC细胞系发生EMT,观察不同转录因子和信号通路的表达。TNF-α处理后TPC-1、Snail和ZEB 2 mRNA表达水平无明显变化,而Slug、Twist 1、ZEB 1 mRNA表达增加。BCPAP组Snail mRNA表达显著增加(P < 0.01),Twist 1仅在TNF - α浓度为20 ng / ml时有一定程度的增加(P < 0.01),而Slug、ZEB 1、ZEB 2 mRNA表达无明显变化。蛋白质表达与基因表达一致。不同通路的激活未表现出基因差异,通路抑制剂可降低细胞的侵袭转移,但只有NF-κB抑制剂可逆转转录因子的表达。Snail和Slug在不同PTC细胞系中的表达依赖于原癌基因突变,但表达途径无差异。该研究模型的建立可以丰富甲状腺癌发病机制和转移的研究,有效地将炎症微环境与甲状腺癌的发生发展联系起来。
Proinflammatory factor tumor necrosis factor-α (TNF-α) is an important inflammatory mediators in tumor microenvironment and autoimmune diseases, it is highly expressed in many solid tumors and tumor microenvironment, showing a tumor promoting role. However, the molecular mechanisms underlying TNF-α-increased invasion of thyroid cancer are still not fully understood. In order to explore whether TNF-α plays a key role in the process of epithelial mesenchymal transition (EMT) in papillary thyroid carcinoma (PTC), we used TNF-α to induce EMT in different PTC cell lines, and observed the expression of different transcription factors and signal pathways. After TNF-α treatment, in TPC-1, Snail and ZEB2 mRNA levels did not change significantly, while Slug, Twist1, ZEB1 mRNA expression increased. In BCPAP, Snail mRNA level increased significantly (P < 0.01), while Twist1 showed a certain degree of increase only at the concentration of TNF - α 20 ng / ml (P < 0.01), but mRNA of Slug, ZEB1, ZEB2 showed no significant change. The expression of proteins was consistent with genes. The activation of different pathways did not show gene differences, and pathway inhibitors could reduce the invasion and metastasis of cells, but only NF-κB inhibitors could reverse the expression of transcription factors. Expressions of Snail and Slug in different PTC cell lines were dependent on pro-oncogene mutation, but the pathway had no differences. The establishment of this study model can enrich the research on the pathogenesis and metastasis of thyroid cancer, effectively link the inflammatory microenvironment with the occurrence and development of thyroid cancer.
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