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微小RNA-615通过抑制己糖激酶2（HK2）在骨肉瘤中发挥肿瘤抑制作用。

MicroRNA-615 functions as a tumor suppressor in osteosarcoma through the suppression of HK2.

作者信息

Sun Limin, Wang Peng, Zhang Zhiqiang, Zhang Kai, Xu Zheng, Li Siyuan, Mao Junsheng

机构信息

Department of Orthopedics, Shandong Provincial Third Hospital, Jinan, Shandong 250031, P.R. China.

Department of Orthopedic Surgery, Taishan Hospital of Shandong Province, Tai'an, Shandong 271000, P.R. China.

出版信息

Oncol Lett. 2020 Nov;20(5):226. doi: 10.3892/ol.2020.12089. Epub 2020 Sep 11.

DOI:10.3892/ol.2020.12089
PMID:32968448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7500052/
Abstract

At present, the regulatory mechanisms of various microRNAs (miRNAs/miRs) have been elucidated in human cancers including osteosarcoma (OS). This study mainly focused on the role of miR-615 in OS, which has not yet been reported. Ninety-two OS tissues and normal samples were used in this study. Human osteoblast hFOB1.19 cells and OS cell line HOS were utilized to detect the expression of miR-615. The expression of miR-615 and gene expression were assessed by RT-qPCR and western blot analysis. Transwell, MTT and luciferase reporter assays were used to investigate the regulatory mechanism of miR-615 in OS. The results revealed that miR-615 expression was reduced in OS tissues and cells, and was associated with poor clinical outcomes and prognosis in OS patients. In addition, overexpression of miR-615 restrained cell viability and metastasis in OS. Furthermore, hexokinase 2 (HK2) was confirmed as a direct target of miR-615. Upregulation of HK2 was detected in OS tissues. The upregulation of HK2 weakened the tumor-suppressive effect of miR-615 in OS. Moreover, miR-615 blocked epithelial-mesenchymal transition (EMT) and inactivated the PI3K/AKT pathway in OS. To conclude, miR-615 acts as a tumor suppressor in OS, thus miR-615 can be used as a target for OS treatment.

摘要

目前，包括骨肉瘤（OS）在内的多种人类癌症中，各种微小RNA（miRNA/miR）的调控机制已得到阐明。本研究主要聚焦于miR-615在骨肉瘤中的作用，这尚未见报道。本研究使用了92例骨肉瘤组织和正常样本。利用人成骨细胞hFOB1.19细胞和骨肉瘤细胞系HOS检测miR-615的表达。通过RT-qPCR和蛋白质免疫印迹分析评估miR-615的表达和基因表达。采用Transwell、MTT和荧光素酶报告基因检测法研究miR-615在骨肉瘤中的调控机制。结果显示，miR-615在骨肉瘤组织和细胞中的表达降低，且与骨肉瘤患者不良的临床结局和预后相关。此外，miR-615的过表达抑制了骨肉瘤细胞的活力和转移。此外，己糖激酶2（HK2）被确认为miR-615的直接靶点。在骨肉瘤组织中检测到HK2的上调。HK2的上调减弱了miR-615在骨肉瘤中的抑癌作用。此外，miR-615在骨肉瘤中阻断上皮-间质转化（EMT）并使PI3K/AKT通路失活。综上所述，miR-615在骨肉瘤中发挥抑癌作用，因此miR-615可作为骨肉瘤治疗的靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/7500052/57c39171a3a9/ol-20-05-12089-g05.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/7500052/dab904ff2f30/ol-20-05-12089-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c181/7500052/5cc43b711287/ol-20-05-12089-g02.jpg
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