Long noncoding RNA H19 competitively binds miR-17-5p to regulate YES1 expression in thyroid cancer
Long noncoding RNA H19 competitively binds miR-17-5p to regulate YES1 expression in thyroid cancer
复制标题
长非编码RNA H19竞争性结合miR-17-5p调节甲状腺癌中YES1的表达
DOI：
10.1111/febs.13741
复制
发表时间：
2016-06-01
期刊：
影响因子：
5.4
通讯作者：
Zhang, Xiaoping
中科院分区：
文献类型：
--
作者：
Liu, Lin;Yang, Jian;Zhang, Xiaoping
长的非编码RNA H19在许多癌症中过度表达，并作为癌基因发挥作用。在这里，我们研究了H19在甲状腺癌发生中的作用及其与microRNA miR-17-5p及其靶基因YES1的关系。H19在肿瘤组织和甲状腺癌细胞系中的表达高于非肿瘤组织和正常甲状腺细胞。H19基因敲除和异位表达在TPC-1和NIM甲状腺癌细胞系中的表达表明，H19基因的过表达促进了细胞的增殖、迁移和侵袭，而H19基因敲除降低了细胞的存活率和侵袭能力，并在体内外诱导了生长停滞。通过双荧光素酶报告试验和RNA结合蛋白免疫沉淀试验，确定H19为miR-17-5p的靶标。H19拮抗miR-17-5p上调靶YES1的作用，抑制miR-17-5p诱导的细胞周期进程。我们的结果表明，H19通过作为miR-17-5p的接收器而发挥竞争内源RNA(Cerna)的作用，揭示了涉及H19和miR-17-5p的潜在的Cerna调控网络，在YES1表达的调控中发挥作用。这一机制可能有助于更好地了解甲状腺癌的发病机制，并为该病的治疗提供新的见解。
The long noncoding RNA H19 is overexpressed in many cancers and acts as an oncogene. Here, we investigated the role of H19 in thyroid carcinogenesis and its relation to microRNA miR-17-5p and its target gene YES1. H19 expression was higher in tumor samples and in thyroid cancer cell lines than nontumor tissues and normal thyroid cells. H19 knockdown and ectopic expression in the TPC-1 and NIM thyroid cancer cell lines showed that overexpression of H19 promoted proliferation, migration, and invasion, whereas H19 knockdown reduced cell viability and invasion and induced growth arrest in vitro and in vivo. H19 was identified as a target of miR-17-5p, by Dual-Luciferase Reporter assays and RNA-binding protein immunoprecipitation assays. H19 antagonized the function of miR-17-5p on upregulation of its target YES1 and inhibited miR-17-5p-induced cell cycle progression. Our results suggest that H19 functions as a competitive endogenous RNA (ceRNA) by acting as a sink for miR-17-5p, revealing a potential ceRNA regulatory network involving H19 and miR-17-5p with a role in the modulation of YES1 expression. This mechanism may contribute to a better understanding of thyroid cancer pathogenesis and provide new insights into the treatment of this disease.