MicroRNA-146b-5p as an oncomiR promotes papillary thyroid carcinoma development by targeting CCDC6
MicroRNA-146b-5p as an oncomiR promotes papillary thyroid carcinoma development by targeting CCDC6
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DOI：
10.1016/j.canlet.2018.11.026
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发表时间：
2019-01-01
期刊：
影响因子：
9.7
通讯作者：
Wang, Jiaxiang
中科院分区：
文献类型：
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作者：
Jia, Meng;Shi, Yang;Wang, Jiaxiang
已知MicroRNA-146b-5p（miR-146b-5p）参与甲状腺乳头状癌的发展（PTC）；但是，基本机制尚不清楚。在这里，我们研究了PTC中miR-146b-5p的生物学功能和基本分子机制。在92对PTC和相邻的正常组织中评估了miR-146b-5p的表达，并显示出与临床病理学状态（例如肿瘤大小）的相关性。 miR-146b-5p及其直接靶标，包含6（CCDC6），对细胞增殖，迁移，侵袭和细胞周期的影响，通过体外增益和功能丧失研究评估。在187例PTC病例中进一步检查了CCDC6的表达，并发现与临床病理状况相关。在与晚期PTC相关的PTC组织中观察到miR-146b-5p的过表达。 miR-146b-5p在体外促进了细胞增殖，迁移，侵袭和细胞周期进程，而CCDC6逆转了这种影响。 miR-146b-5p在体内促进了皮下小鼠模型中的PTC生长，而CCDC6的过表达施加了相反的效果。总之，miR-146b-5p表达与晚期PTC相关，并通过靶向CCDC6体外和体内促进PTC发育。因此，它可以作为PTC治疗的有希望的目标。
The microRNA-146b-5p (miR-146b-5p) is known to be involved in the development of papillary thyroid cancer (PTC); however, the underlying mechanism is unclear. Here we have investigated the biological functions and underlying molecular mechanisms of miR-146b-5p in PTC. The expression of miR-146b-5p was assessed in 92 pairs of PTC and adjacent normal tissues and showed correlation with the clinicopathological status such as the tumour size. Effects of miR-146b-5p and its direct target, coiled-coil domain containing 6 (CCDC6), on cell proliferation, migration, invasion, and cell cycle were evaluated through gain- and loss-of-function studies in vitro and in vivo. The expression of CCDC6 was further examined in 187 PTC cases and was found to be correlated with the clinicopathological status. Overexpression of miR-146b-5p was observed in PTC tissues that correlated with advanced PTC. miR-146b-5p promoted cell proliferation, migration, invasion, and cell cycle progression in vitro, whereas CCDC6 reversed this effect. miR-146b-5p promoted PTC growth in a subcutaneous mouse model in vivo, whereas overexpression of CCDC6 exerted the opposite effect. In conclusion, miR-146b-5p expression correlated with advanced PTC and promoted PTC development by targeting CCDC6 in vitro and in vivo; it could, therefore, serve as a promising target for PTC treatment.