微小RNA-219-5p通过靶向雌激素受体α调控甲状腺乳头状癌的细胞生长。
miR-219-5p modulates cell growth of papillary thyroid carcinoma by targeting estrogen receptor α.
作者信息
Huang Chen, Cai Zhaogeng, Huang Mingzhu, Mao Chaoming, Zhang Qifa, Lin Yi, Zhang Xiaomei, Tang Bi, Chen Yuqing, Wang Xiaojing, Qian Zhongqing, Ye Lei, Peng Yongde, Xu Huanbai
机构信息
Department of Endocrinology and Metabolism and Department of General Surgery (C.H., Y.L. Y.P., H.X.), Shanghai Jiaotong University Affiliated First People's Hospital, Shanghai 200080, China; Department of Endocrinology and Metabolism (Z.C., X.Z., B.T., Y.C., X.W., Z.Q., H.X.), Anhui Clinical and Preclinical Key Laboratory of Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; Department of Medical Oncology (Q.Z.), Fudan University Shanghai Cancer Center (M.H.); Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China; Department of Nuclear Medicine or Institute of Oncology (C.M.), The Hospital Affiliated to Jiangsu University, Zhenjiang 212001, China; Department of Urology (Q.Z.), Shanghai Traditional Chinese and Medicine Integrated Hospital, Shanghai 200082, China; and Department of Endocrinology and Metabolism (L.Y.), Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
出版信息
J Clin Endocrinol Metab. 2015 Feb;100(2):E204-13. doi: 10.1210/jc.2014-2883. Epub 2014 Nov 25.
CONTEXT
Papillary thyroid carcinoma (PTC) is the most common endocrine malignancy. It has been demonstrated that micro-RNAs (miRNAs) are involved in the development of PTC. The miRNA-chromatin immunoprecipitation microarray assay revealed down-regulation of miR-219-5p; however, the effect of miR-219-5p on PTC cell growth remains unknown. This result implied the critical role of miR-219-5p in the development of PTC.
METHODS
We investigated the association between miR-219-5p and PTC development. Expression of miR-219-5p was monitored in 30 PTC tissue specimens and compared with that in 30 normal thyroid tissue specimens. The effect of miR-219-5p on PTC development was studied by cell proliferation, migration, and apoptosis assays. The underlying mechanism was clarified by a reporter assay and rescue experiment.
RESULTS
The current study confirmed that miR-219-5p expression was inhibited in PTC tissue samples. There were statistically significant differences in the expression of miR-219-5p with regard to sex, tumor size, and lymph node metastasis in patients with PTC. Forced expression of miR-219-5p suppressed PTC cell proliferation and migration and promoted apoptosis. Further study showed that estrogen receptor (ER) α was the direct target of miR-219-5p and mediated the effect of miR-219-5p on PTC occurrence. Expression of miR-219-5p was inversely correlated with that of ERα. Importantly, ERα overexpression in PTC cells rescued the inhibitory effect of miR-219-5p on PTC cell proliferation and migration. Thus, our results indicated that miR-219-5p played a critical role in PTC growth by inhibiting ERα.
CONCLUSION
Our investigation identified miR-219-5p as a negative regulator of PTC development through targeting of ERα.
背景
甲状腺乳头状癌（PTC）是最常见的内分泌恶性肿瘤。已有研究表明，微小RNA（miRNA）参与了PTC的发生发展。miRNA-染色质免疫沉淀微阵列分析显示miR-219-5p表达下调；然而，miR-219-5p对PTC细胞生长的影响尚不清楚。这一结果提示miR-219-5p在PTC发生发展中起关键作用。
方法
我们研究了miR-219-5p与PTC发生发展之间的关联。检测了30例PTC组织标本中miR-219-5p的表达，并与30例正常甲状腺组织标本进行比较。通过细胞增殖、迁移和凋亡实验研究miR-219-5p对PTC发生发展的影响。通过报告基因实验和拯救实验阐明其潜在机制。
结果
本研究证实PTC组织样本中miR-219-5p表达受到抑制。PTC患者中，miR-219-5p的表达在性别、肿瘤大小和淋巴结转移方面存在统计学显著差异。miR-219-5p的强制表达抑制了PTC细胞的增殖和迁移，并促进了细胞凋亡。进一步研究表明，雌激素受体（ER）α是miR-219-5p的直接靶点，并介导了miR-219-5p对PTC发生的影响。miR-219-5p的表达与ERα的表达呈负相关。重要的是，PTC细胞中ERα的过表达挽救了miR-219-5p对PTC细胞增殖和迁移的抑制作用。因此，我们的结果表明miR-219-5p通过抑制ERα在PTC生长中起关键作用。
结论
我们的研究确定miR-219-5p通过靶向ERα是PTC发生发展的负调节因子。
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