Key Lab of Etiology and Epidemiology, National Health and Family Planning Commission, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.
Department of Biochemistry and Molecular Biology, Harbin Medical University, Harbin, Heilongjiang, China.
J Mol Endocrinol. 2020 Aug;65(2):1-10. doi: 10.1530/JME-19-0198.
miR-146b-5p is overexpressed in papillary thyroid carcinoma (PTC) and is thought to be a related diagnostic marker. Previous studies have indicated the effects of iodine on oncogenic activation. However, the effect of iodine on the proliferation of PTC cells and the associated underlying mechanisms remain unclear. We found that miR-146b-5p was downregulated and smad4 was upregulated in patients exposed to high iodine concentration by in situ hybridisation (ISH) and immunohistochemical (IHC). NaI (10-3 M) treatment downregulated miR-146b-5p and upregulated Smad4 in PTC cell lines. Luciferase assay was used to confirm that Smad4 is a target of miR-146b-5p. Furthermore, MTT assay and cell cycle analysis indicated that 10-3 M NaI suppressed cell proliferation and caused G0/G1 phase arrest. Real-time PCR and Western blotting demonstrated that 10-3 M NaI increased p21, p27, and p57 levels and reduced cyclin D1 levels in PTC cells. Our findings suggest that 10-3 M NaI increases Smad4 levels through repression of miR-146b-5p expression, curbing the proliferation in PTC.
miR-146b-5p 在甲状腺乳头状癌（PTC）中过表达，被认为是相关的诊断标志物。先前的研究表明碘对致癌基因的激活有影响。然而，碘对 PTC 细胞增殖的影响及其相关的潜在机制仍不清楚。我们发现，原位杂交（ISH）和免疫组织化学（IHC）显示，高碘浓度暴露的患者中 miR-146b-5p 下调，smad4 上调。NaI（10-3 M）处理下调 PTC 细胞系中的 miR-146b-5p 并上调 Smad4。荧光素酶测定用于证实 Smad4 是 miR-146b-5p 的靶标。此外，MTT 分析和细胞周期分析表明，10-3 M NaI 抑制细胞增殖并导致 G0/G1 期阻滞。实时 PCR 和 Western blot 表明，10-3 M NaI 增加 PTC 细胞中 p21、p27 和 p57 的水平，并降低 cyclin D1 的水平。我们的研究结果表明，10-3 M NaI 通过抑制 miR-146b-5p 的表达增加 Smad4 水平，从而抑制 PTC 的增殖。
