KIAA1199, a Target of Micoro-486-5p, Promotes Papillary Thyroid Cancer Invasion by Influencing Epithelial-Mesenchymal Transition (EMT)
KIAA1199, a Target of Micoro-486-5p, Promotes Papillary Thyroid Cancer Invasion by Influencing Epithelial-Mesenchymal Transition (EMT)
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DOI：
10.12659/msm.918682
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发表时间：
2019-09-10
影响因子：
3.1
通讯作者：
Cheng, Xingbo
中科院分区：
文献类型：
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作者：
Jiao, Xuehua;Ye, Jiandong;Cheng, Xingbo
背景：KIAA 1199已被报道与各种人类恶性肿瘤的恶性进展和不良临床结局相关。材料/方法：应用肿瘤基因组图谱（TCGA）分析KIAA 1199和miR-486- 5 p在甲状腺乳头状癌（PTC）中的表达情况。免疫组化法检测KIAA 1199在PTC中的表达。采用加权基因共表达网络分析（WGCNA）和基因集富集分析（GSEA）研究KIAA 1199在PTC中的作用机制。进行体外和体内实验以研究KIAA 1199在PTC进展中的生物学作用。结果：与正常组织相比，KIAA 1199在PTC组织中的表达水平显著升高，且KIAA 1199的上调与更晚期的临床变量呈正相关。此外，生物信息学分析表明KIAA 1199参与细胞迁移和侵袭。KIAA 1199沉默通过影响上皮-间质转化（EMT）抑制PTC细胞的侵袭能力。结论：miR-486 - 5 p/KIAA 1199/EMT轴可能在PTC的侵袭和转移过程中发挥重要作用，为PTC的治疗提供了一种新的思路。
Background: KIAA1199 has been reported to be associated with malignant progression and poor clinical outcomes in var- ious human malignancies. However, its clinical role and molecular function remain unknown in papillary thyroid cancer (PTC).Material/Methods: The Cancer Genome Atlas (TCGA) was used to investigate the expression profiles of KIAA1199 and miR-486-5p in PTC. Immunohistochemistry was used to validate the protein expression of KIAA1199 in PTC. The Weighted Gene Co-expression Network Analysis (WGCNA) and Gene Set Enrichment Analysis (GSEA) were used to explore the potential pathway underling KIAA1199 in PTC. In vitro and in vivo experiments were performed to investigate the biological role of KIAA1199 in PTC progression. Luciferase reporter assays and Western blot analysis were performed to determine whether KIAA1199 is a downstream target of miR-486-5p.Results: We found that KIAA1199 was aberrantly elevated in PTC tissues compared with normal tissues, and upregu- lation of KIAA1199 was positively correlated with more advanced clinical variables. Additionally, bioinformatic analysis indicated that KIAA1199 was involved in cell migration and invasion. KIAA1199 silencing inhibited the invasive ability of PTC cells by affecting epithelial-mesenchymal transition (EMT) in vitro and in vivo. Furthermore, miR-486-5p was identified as an upstream microRNA that directly targets the 3'-UTR region of KIAA1199.Conclusions: The miR-486-5p/KIAA1199/EMT axis might play a critical role in PTC invasion and metastasis and offers a potential therapeutic strategy for PTC.