Department of Medical Genetics, Faculty of Medicine, Tehran University of Medical Sciences, Poursina St, Tehran, Iran.
Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Poursina St, District 6, Tehran, Tehran Province, Iran.
Mol Biol Rep. 2020 Mar;47(3):2161-2169. doi: 10.1007/s11033-020-05315-8. Epub 2020 Feb 18.
FSCN1 gene encodes an actin-bundling protein, FSCN1, which is involved in formation of actin-based structures that contribute to cell migration. High levels of FSCN1 expression is observed in cells with extended membranes and protrusions. Moreover, up-regulation of FSCN1 has been reported in several epithelial carcinomas. Therefore, FSCN1 is thought to play a role in cell movement and invasion. However, the mechanism behind FSCN1 up-regulation is not known. We investigated the expression of FSCN1 using immunohistochemistry. Methylation-specific PCR was adopted to analyze the methylation status of FSCN1 promoter as a potential regulatory mechanism in FSCN1 expression. The samples included papillary thyroid carcinoma, follicular thyroid carcinoma and goiter samples (controls). Methylation of FSCN1 promoter was observed in 50% of follicular, 48.6% of papillary and 60% of controls. The promoter was unmethylated in 16.7% of follicular samples, 5.7% of papillary samples and 26.7% of controls. In the remaining 33.3% of follicular and 45.7% of papillary samples as well as 13.3% of controls, both methylated and unmethylated alleles were amplified, a condition referred to as semi-methylation. The results showed that FSCN1 promoter was significantly hypomethylated in papillary cases while the methylation status was not significantly altered in follicular cases. On the other hand, FSCN1 was expressed in only nine papillary samples. Regarding protein expression and methylation status, we suggest that hypomethylation of FSCN1 promoter in papillary thyroid carcinoma does not lead to overexpression of FSCN1 and that there might be other regulatory mechanisms involved in FSCN1 up-regulation.
FSCN1 基因编码一种肌动蛋白结合蛋白 FSCN1，该蛋白参与肌动蛋白为基础的结构的形成，这些结构有助于细胞迁移。在具有延伸的膜和突起的细胞中观察到 FSCN1 的高表达。此外，在几种上皮癌中已经报道了 FSCN1 的上调。因此，FSCN1 被认为在细胞运动和侵袭中发挥作用。然而，FSCN1 上调的机制尚不清楚。我们使用免疫组织化学研究了 FSCN1 的表达。采用甲基化特异性 PCR 分析 FSCN1 启动子的甲基化状态作为 FSCN1 表达的潜在调节机制。样本包括甲状腺乳头状癌、滤泡性甲状腺癌和甲状腺肿样本（对照）。在滤泡性肿瘤中观察到 FSCN1 启动子甲基化的占 50%，在乳头状肿瘤中为 48.6%，在对照组中为 60%。在 16.7%的滤泡性肿瘤样本、5.7%的乳头状肿瘤样本和 26.7%的对照组中，启动子未甲基化。在滤泡性肿瘤和乳头状肿瘤中分别有 33.3%和 45.7%的样本以及对照组中 13.3%的样本中，扩增出甲基化和未甲基化的等位基因，这种情况称为半甲基化。结果表明，在乳头状肿瘤中 FSCN1 启动子明显低甲基化，而在滤泡性肿瘤中甲基化状态没有明显改变。另一方面，FSCN1 仅在 9 个乳头状肿瘤样本中表达。关于蛋白表达和甲基化状态，我们认为甲状腺乳头状癌中 FSCN1 启动子的低甲基化不会导致 FSCN1 的过表达，可能涉及其他调节机制。
