MicroRNA‑497 inhibits cellular proliferation, migration and invasion of papillary thyroid cancer by directly targeting AKT3.

MicroRNA‑497 inhibits cellular proliferation, migration and invasion of papillary thyroid cancer by directly targeting AKT3.
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MicroRNA-497直接靶向AKT3抑制甲状腺乳头状癌细胞增殖、迁移和侵袭

DOI:
10.3892/mmr.2017.7345
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发表时间:
2017-11
影响因子:
3.4
通讯作者:
Lv Z
Lv Z
中科院分区:
医学4区
文献类型:
--
作者:
Zhuang J;Ye Y;Wang G;Ni J;He S;Hu C;Xia W;Lv Z

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甲状腺癌是内分泌器官最常见的肿瘤。近年来的研究表明microRNAs(miRs)作为肿瘤抑制因子或癌基因在甲状腺乳头状癌(PTC)的形成和发展中发挥着重要作用。本研究探讨miR-497在PTC中的表达水平、生物学作用及其可能机制。结果表明,在PTC组织和细胞系中,miR-497的表达水平均降低。miR-497的增强表达抑制PTC细胞增殖、迁移和侵袭。通过生物信息学分析、荧光素酶报告基因分析、逆转录-定量聚合酶链反应(RT-PCR)和蛋白质印迹分析,证实RAC-γ丝氨酸/苏氨酸蛋白激酶(AKT 3)是miR-497的直接靶基因。此外,PTC组织中AKT 3表达增加,并与miR-497表达呈负相关。此外,AKT 3的下调也抑制了PTC细胞的增殖、迁移和侵袭,这与miR-497在PTC细胞中的过表达具有相似的作用。综上所述,这些结果表明,这种新发现的miR-497/AKT 3信号通路可能有助于PTC的发生和进展。这些发现为PTC的治疗提供了新的潜在的治疗靶点。
Thyroid cancer is the most common tumor of the endocrine organs. Emerging studies have indicated the critical roles of microRNAs (miRs) in papillary thyroid cancer (PTC) formation and progression through function as tumor suppressors or oncogenes. The present study investigated the expression level and biological roles of miR-497 in PTC and its underlying mechanisms. It was demonstrated that the expression level of miR-497 was reduced in both PTC tissues and cell lines. Enforced expression of miR-497 suppressed PTC cell proliferation, migration and invasion. According to bioinformatics analysis, a luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction and western blotting, RAC-γ serine/threonine-protein kinase (AKT3) was demonstrated to be the direct target gene of miR-497. In addition, AKT3 expression increased in PTC tissues and negatively correlated with miR-497 expression. Furthermore, downregulation of AKT3 also suppressed cell proliferation, migration and invasion of PTC, which had similar roles to miR-497 overexpression in PTC cells. Taken together, these results suggested that this newly identified miR-497/AKT3 signaling pathway may contribute to PTC occurrence and progression. These findings provide novel potential therapeutic targets for the therapy of PTC.
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