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Huimei Yang,1 Zhenzhen Song,1 Xia Wu,2 Yilei Wu,2 Chengxia Liu31Department 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 Pathology, Linyi Cancer Hospital, Linyi, Shandong 276023, People’s Republic of ChinaPurpose: An increasing number of studies have documented that dysregulation of microRNAs (miRNAs) is common in glioblastoma multiforme (GBM). miR-652 is aberrantly expressed in various human cancers and plays important roles in numerous cancer-related processes. However, the expression profiles and potential roles of miR-652 in GBM remain largely unknown.Patients and methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine miR-652 expression in GBM tissues and cell lines. The effects of miR-652 upregulation on GBM cell proliferation, clone formation, apoptosis, migration and invasion were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, clone formation, flow cytometry and Transwell®migration and invasion assays, respectively. In vivo xenotransplantation was utilized to determine the effect of miR-652 on GBM tumor growth in vivo. Of note, the molecular mechanisms underlying the tumor-suppressing activity of miR-652 upregulation in GBM cells were also investigated using a series of experiments, including bioinformatics analysis, luciferase reporter assay, RT-qPCR and Western blot analysis.Results: miR-652 expression was considerably downregulated in GBM tissues and cell lines. Low miR-652 expression was strongly correlated with Karnofsky performance score and tumor size. Overall survival duration was shorter in GBM patients with low miR-652 expression than in those with high miR-652 expression. miR-652 resumption considerably suppressed the proliferation, clone formation, migration, and invasion and promoted the apoptosis of GBM cells in vitro. In addition, forkhead-box k1 (FOXK1) was demonstrated as the direct target gene of miR-652 in GBM cells. FOXK1 downregulation led to a tumor-suppressing activity similar to that of miR-652 upregulation. Restoration of FOXK1 expression partially neutralized the influence of miR-652 overexpression on GBM cells. Furthermore, ectopic miR-652 expression deactivated the AKT/mTOR pathway in GBM cells via FOXK1 regulation. Moreover, miR-652 impaired GBM tumor growth in vivo, probably caused by miR-652-mediated suppression of FOXK1/AKT/mTOR signaling.Conclusion: miR-652 inhibits FOXK1 and deactivates the AKT/mTOR pathway, thereby resulting in the suppression of malignant phenotypes of GBM cells in vitro and in vivo.Keywords: glioblastoma multiforme, microRNA, Forkhead-box K1, malignant development

Zhenzhen Song,1 Huimei Yang,1 Xia Wu,2 Cui Kong,2 Cong’e Xu31Department 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 ChinaBackground: 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