长链非编码 RNA HAGLROS 通过调节 miR-206/HMGA2 的表达促进甲状腺乳头状癌的进展。
LncRNA HAGLROS contribute to papillary thyroid cancer progression by modulating miR-206/HMGA2 expression.
机构信息
Department of Nuclear Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha 410001, Hunan, China.
Chenzhou First People’s Hospital, Beihu, Chenzhou 423000, Hunan, China.
出版信息
Aging (Albany NY). 2023 Dec 18;15(24):14930-14944. doi: 10.18632/aging.205321.
OBJECTIVE
Papillary thyroid cancer (PTC) is one of the most serious diseases of the endocrine system. In view of the limited therapeutic effects of current medical methods, this study starts from the molecular level and looks for potential treatments. The interaction between HAGLROS/miR-206/HMGA2 was studied using multi-omics methods, which provided new ideas and methods for future treatments.
METHOD
Microarray analysis and R language were used for differential analysis to screening experimental targets of lncRNA, miRNA, and mRNA. qRT-PCR was used to detect RNA expression in tissues and cells. Double luciferase reporter assays analyzed and validated binding relationships between different RNAs. Colony formation, flow cytometry, and transwell assays were used to measure the effect of them on cell proliferation, apoptosis, and migration.
RESULT
Microarray analysis identified lncRNAs, miRNAs, and mRNAs differentially expressed in PTC and normal cells, and selected lncRNA HAGLROS, miR-206, and mRNA HMGA2 as study subjects. LncRNA HAGLROS and mRNA HMGA2 were highly expressed in PTC cells while miR-206 was lowly expressed in PTC cells. LncRNA HAGLROS/HMGA2 can inhibit apoptosis of PTC cells, promote proliferation and migration, and miR-206 promotes the above process. HAGLROS and HMGA2 were negatively correlated with miR-206. shHAGLROS promoted miR-206 expression, inhibited HMGA2 expression and repressed PTC tumor growth in mice.
CONCLUSIONS
HAGLROS promotes the growth of PTC by competitively binding to miR-206 to promote HMGA2 expression.
目的
甲状腺乳头状癌（PTC）是内分泌系统最严重的疾病之一。鉴于目前医学方法的治疗效果有限，本研究从分子水平出发，寻找潜在的治疗方法。采用多组学方法研究 HAGLROS/miR-206/HMGA2 的相互作用，为未来的治疗提供了新的思路和方法。
方法
采用微阵列分析和 R 语言进行差异分析，筛选 lncRNA、miRNA 和 mRNA 的实验靶点。qRT-PCR 用于检测组织和细胞中 RNA 的表达。双荧光素酶报告实验分析和验证不同 RNA 之间的结合关系。集落形成、流式细胞术和 Transwell 实验用于测量它们对细胞增殖、凋亡和迁移的影响。
结果
微阵列分析鉴定了 PTC 和正常细胞中差异表达的 lncRNA、miRNA 和 mRNA，选择 lncRNA HAGLROS、miR-206 和 mRNA HMGA2 作为研究对象。lncRNA HAGLROS 和 mRNA HMGA2 在 PTC 细胞中高表达，而 miR-206 在 PTC 细胞中低表达。lncRNA HAGLROS/HMGA2 可抑制 PTC 细胞凋亡，促进增殖和迁移，而 miR-206 促进上述过程。HAGLROS 和 HMGA2 与 miR-206 呈负相关。shHAGLROS 促进 miR-206 表达，抑制 HMGA2 表达，抑制小鼠 PTC 肿瘤生长。
结论
HAGLROS 通过与 miR-206 竞争结合来促进 HMGA2 表达，从而促进 PTC 的生长。
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