Song Zhenzhen, Yang Huimei, Wu Xia, Kong Cui, Xu Cong'e
Department of Laboratory, The Third People's Hospital of Linyi, Linyi, Shandong 276023, People's Republic of China.
Department of Oncology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, People's Republic of China.
Onco Targets Ther. 2019 Jun 28;12:4869-4881. doi: 10.2147/OTT.S201282. eCollection 2019.
Accumulating evidence has revealed that an increasing number of microRNAs (miRNAs) are dysregulated in papillary thyroid cancer (PTC) and that their dysregulation plays an important role in PTC onset and progression. Reportedly, miRNA-564 (miR-564) is downregulated in several types of human cancer. However, its expression profile and specific functions in PTC remain unclear to date. In this study, we used reverse transcription-quantitative polymerase chain reaction to detect miR-564 expression in PTC tissues and cell lines. Further, the regulatory roles of miR-564 in the malignant development of PTC in vitro and in vivo were examined using a series of functional experiments. In addition, the possible underlying mechanisms and signaling pathways involved were investigated. We demonstrated that miR-564 expression markedly decreased in PTC tissues and cell lines, and this decrease correlated with the lymph node metastasis and tumor-node-metastasis stage. miR-564 upregulation significantly inhibited cell proliferation, migration, and invasion and induced cell apoptosis in vitro as well as hindered tumor growth in vivo. Furthermore, astrocyte-elevated gene-1 (AEG-1) was identified as a direct target gene of miR-564 in PTC cells. Its expression was upregulated and inversely correlated with miR-564 expression in clinically PTC tissues. Additionally, the silencing of AEG-1 expression could imitate the action of miR-564 overexpression in PTC cells. Remarkably, the restoration of AEG-1 expression partially abolished the tumor-suppressing effects induced by a miR-564 upregulation in PTC cells. Ectopic miR-564 expression deactivated the PTEN/Akt pathway in PTC cells in vitro and in vivo. Overall, the findings of the current study suggest that miR-564 is a tumor-suppressive miRNA that exerts crucial roles in the development and progression of PTC. Therefore, this miRNA might be a promising candidate target in the anticancer treatment of patients with PTC.
越来越多的证据表明，在乳头状甲状腺癌（PTC）中，越来越多的微小RNA（miRNA）表达失调，且它们的失调在PTC的发生和发展中起重要作用。据报道，miRNA-564（miR-564）在几种类型的人类癌症中表达下调。然而，其在PTC中的表达谱和具体功能迄今仍不清楚。在本研究中，我们使用逆转录定量聚合酶链反应检测PTC组织和细胞系中miR-564的表达。此外，通过一系列功能实验研究了miR-564在PTC体外和体内恶性发展中的调控作用。另外，还研究了可能涉及的潜在机制和信号通路。我们证明，miR-564在PTC组织和细胞系中的表达明显降低，且这种降低与淋巴结转移和肿瘤-淋巴结-转移分期相关。miR-564上调显著抑制体外细胞增殖、迁移和侵袭并诱导细胞凋亡，以及在体内抑制肿瘤生长。此外，星形胶质细胞升高基因1（AEG-1）被鉴定为PTC细胞中miR-564的直接靶基因。在临床PTC组织中，其表达上调且与miR-564表达呈负相关。此外，沉默AEG-1表达可模拟miR-564过表达在PTC细胞中的作用。值得注意的是，恢复AEG-1表达部分消除了miR-564上调在PTC细胞中诱导的肿瘤抑制作用。异位表达miR-564使PTC细胞在体外和体内的PTEN/Akt通路失活。总体而言，本研究结果表明，miR-564是一种肿瘤抑制性miRNA，在PTC的发生和发展中发挥关键作用。因此，这种miRNA可能是PTC患者抗癌治疗中有前景的候选靶点。
