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微小RNA-208a-3p通过靶向磷酸酶和张力蛋白同源物(PTEN)促进骨肉瘤进展。

MicroRNA-208a-3p promotes osteosarcoma progression via targeting PTEN.

作者信息

Fu Yutuo, Wang Yan, Bi Ke, Yang Lei, Sun Yi, Li Boyuan, Liu Zhenzhong, Zhang Fulin, Li Yuan, Feng Chao, Bi Zhenggang

机构信息

Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, P.R. China.

Department of Orthopedics, Heilongjiang Provincial Hospital, Harbin, Heilongjiang 150000, P.R. China.

出版信息

Exp Ther Med. 2020 Dec;20(6):255. doi: 10.3892/etm.2020.9385. Epub 2020 Oct 23.

DOI:10.3892/etm.2020.9385
PMID:33178353
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7651880/
Abstract

Osteosarcoma (OS) is a malignant bone tumor with a poor prognosis. Accumulated evidence has suggested that microRNAs (miRNAs/miRs) may function as either oncogenes or tumor suppressors, which are associated with tumorigenesis and the progression of different types of cancer. In the present study, the role of miR-208a-3p in OS was investigated. The expression levels of miR-208a-3p in OS tissues and cell lines were determined via reverse transcription-quantitative PCR (RT-qPCR). MTT and colony formation assays were performed to verify the proliferation rate of OS cells. In addition, the effects of miR-208a-3p on the migration and invasion of OS cells were revealed using wound-healing and Transwell assays, respectively. Furthermore, the association between miR-208a-3p and phosphatase and tensin homolog (PTEN) 3'-untranslated region was determined via luciferase reporter assays, western blot and RT-qPCR analysis. The results indicated that miR-208a-3p was upregulated in OS tissues and cell lines compared with adjacent normal tissues and human osteoblastic cells, respectively. miR-208a-3p overexpression promoted and miR-208a-3p knockdown inhibited OS cells proliferation and metastatic potential. Additionally, PTEN was validated as a direct target of miR-208a-3p and its expression was negatively associate with that of miR-208a-3p in OS cells. Taken together, these results may suggest that miR-208a-3p promoted OS cells proliferation and metastatic potential via targeting PTEN. Therefore, miR-208a-3p may be considered as a diagnostic biomarker for OS.

摘要

骨肉瘤(OS)是一种预后较差的恶性骨肿瘤。越来越多的证据表明,微小RNA(miRNA/miR)可能作为癌基因或肿瘤抑制因子发挥作用,这与不同类型癌症的发生和进展有关。在本研究中,对miR-208a-3p在骨肉瘤中的作用进行了研究。通过逆转录定量PCR(RT-qPCR)测定骨肉瘤组织和细胞系中miR-208a-3p的表达水平。进行MTT和集落形成试验以验证骨肉瘤细胞的增殖率。此外,分别使用伤口愈合试验和Transwell试验揭示了miR-208a-3p对骨肉瘤细胞迁移和侵袭的影响。此外,通过荧光素酶报告基因试验、蛋白质印迹和RT-qPCR分析确定了miR-208a-3p与磷酸酶和张力蛋白同源物(PTEN)3'-非翻译区之间的关系。结果表明,与相邻正常组织和人成骨细胞相比,miR-208a-3p在骨肉瘤组织和细胞系中分别上调。miR-208a-3p过表达促进,而miR-208a-3p敲低抑制骨肉瘤细胞增殖和转移潜能。此外,PTEN被验证为miR-208a-3p的直接靶标,其表达与骨肉瘤细胞中miR-208a-3p的表达呈负相关。综上所述,这些结果可能表明miR-208a-3p通过靶向PTEN促进骨肉瘤细胞增殖和转移潜能。因此,miR-208a-3p可被视为骨肉瘤的诊断生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/dd1a63406a76/etm-20-06-09385-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/6f31e66440e9/etm-20-06-09385-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/1b6376c71f6a/etm-20-06-09385-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/92e144e49382/etm-20-06-09385-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/224841916d08/etm-20-06-09385-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/7e99f49b121b/etm-20-06-09385-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/dd1a63406a76/etm-20-06-09385-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/6f31e66440e9/etm-20-06-09385-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/1b6376c71f6a/etm-20-06-09385-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/92e144e49382/etm-20-06-09385-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/224841916d08/etm-20-06-09385-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/7e99f49b121b/etm-20-06-09385-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9111/7651880/dd1a63406a76/etm-20-06-09385-g05.jpg

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