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miRNA-101 通过靶向 TGF-βR1 抑制口腔鳞状细胞癌的进展。

miRNA-101 Targets TGF-βR1 to Retard the Progression of Oral Squamous Cell Carcinoma.

机构信息

Department of Pediatric Dentistry, Beijing Stomatological Hospital & School of Stomatology, Capital Medical UniversityBeijingChina.

Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention of PLABeijingChina.

出版信息

Oncol Res. 2020 Mar 27;28(2):203-212. doi: 10.3727/096504019X15761480623959. Epub 2019 Dec 12.

Abstract

Despite the considerable knowledge on the involvement of microRNA-101 (miR-101) in the evolution of oral squamous cell carcinoma (OSCC), the underlying mechanisms remain obscure. In this study, miR-101 expression was markedly downregulated in the OSCC cell lines and tissues. Cell counting kit-8 (CCK-8), ethynyl deoxyuridine (EdU), and colony formation assays showed that miR-101 inhibited the proliferation of OSCC cells. Flow cytometry and caspase 3 activity assays indicated that miR-101 induced OSCC cell apoptosis. Transwell assays demonstrated that this miRNA also repressed OSCC cell migration and invasion. Moreover, tube formation assay showed that miR-101 abated the proangiogenesis of OSCC cells. Dual-luciferase reporter assay confirmed that miR-101 directly targeted transforming growth factor-β receptor 1 (TGF-βR1) in OSCC. Ectopic expression of TGF-βR1 counteracted the effects of miR-101 on the OSCC cell characteristics. Thus, miR-101 significantly abolished the proliferation, motility, and proangiogenesis of OSCC cells and induced their apoptosis by targeting TGF-βR1. These results imply the potential application of miR-101 in OSCC treatment.

摘要

尽管人们对 microRNA-101 (miR-101) 在口腔鳞状细胞癌 (OSCC) 演进中的作用有了相当的了解,但潜在的机制仍不清楚。在这项研究中,miR-101 在 OSCC 细胞系和组织中表达明显下调。细胞计数试剂盒-8 (CCK-8)、乙基脱氧尿苷 (EdU) 和集落形成实验表明,miR-101 抑制 OSCC 细胞的增殖。流式细胞术和 caspase 3 活性测定表明,miR-101 诱导 OSCC 细胞凋亡。Transwell 实验表明,这种 miRNA 还抑制了 OSCC 细胞的迁移和侵袭。此外,管形成实验表明,miR-101 减弱了 OSCC 细胞的促血管生成作用。双荧光素酶报告基因实验证实,miR-101 直接靶向 OSCC 中的转化生长因子-β受体 1 (TGF-βR1)。TGF-βR1 的异位表达抵消了 miR-101 对 OSCC 细胞特性的影响。因此,miR-101 通过靶向 TGF-βR1,显著抑制了 OSCC 细胞的增殖、迁移和促血管生成能力,并诱导其凋亡。这些结果表明 miR-101 在 OSCC 治疗中的潜在应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ee2d/7851522/c6ce7826629c/OR-28-203-g001.jpg

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