microRNA-564 inhibits the aggressive phenotypes of papillary thyroid cancer by directly targeting astrocyte-elevated gene-1
Authors Song Z, Yang H, Wu X, Kong C, Xu C
Received 11 January 2019
Accepted for publication 15 April 2019
Published 28 June 2019 Volume 2019:12 Pages 4869—4881
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Ms Aruna Narula
Peer reviewer comments 2
Editor who approved publication: Professor Jianmin Xu
Zhenzhen Song,1 Huimei Yang,1 Xia Wu,2 Cui Kong,2 Cong’e Xu3
1Department of Laboratory, The Third People’s Hospital of Linyi, Linyi, Shandong 276023, People’s Republic of China; 2Department of Oncology, The Third People’s Hospital of Linyi, Linyi, Shandong 276023, People’s Republic of China; 3Department of Radiation Oncology, Linyi Cancer Hospital, Linyi, Shandong 276000, People’s Republic of China
Background: 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.
Methods: 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.
Results: 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.
Conclusion: 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.
Keywords: microRNA-564, papillary thyroid cancer, astrocyte elevated gene-1, aggressive phenotypes
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