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miR-206 通过靶向 HDAC6 抑制 PTEN/AKT/mTOR 通路抑制头颈部鳞状细胞癌细胞的进展。

MiR-206 inhibits Head and neck squamous cell carcinoma cell progression by targeting HDAC6 via PTEN/AKT/mTOR pathway.

机构信息

Department of Head and Neck Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing Medical University Affiliated Cancer Hospital, Nangjing 210000, China.

Department of Otolaryngology Head and Neck Surgery, Affiliated Hospital of XuZhou Medical University, Xuzhou 221000, China.

出版信息

Biomed Pharmacother. 2017 Dec;96:229-237. doi: 10.1016/j.biopha.2017.08.145. Epub 2017 Oct 6.

DOI:10.1016/j.biopha.2017.08.145
PMID:28987947
Abstract

As a kind of endogenous noncoding small RNA, microRNA (miRNA) plays important roles of regulation to various physiological functions, while its affections on senescence of human Head and neck squamous cell carcinoma (HNSCC) are still unknown. The objective of this study was to investigate the effect of miR-206 in HNSCC tissues, adjacent normal tissues and cell lines, and explore its biological functions in HNSCC. In our study, the level of miR-206 in HNSCC tissues and adjacent normal tissues was detected via real-time qPCR. The effect of miR-206 on cell proliferation was tested by MTT assay, colony formation and cell cycle assays. In order to explore the effect of miR-206 on HNSCC cell migration and invasion, we performed wound healing assays and transwell assays. Luciferase reporter assays were designed to identify the interaction between 3'UTR of HDAC6 and miR-206. The level of signaling pathway-related proteins was determined by western blot. The expression of miR-206 was found to be observably decreased in HNSCC tissues and cell lines through real time-PCR. Restoration of miR-206 weaked cell proliferation, invasion and migration in HNSCC cells and the cell cycle was arrest in S phase. Further explores have shown that miR-206 could inhibit HNSCC cells proliferation by targeting the HDAC6 via PTEN/AKT/mTOR pathway. Taken together, our results demonstrated that miR-206 plays a critical role in HNSCC progression by targeting HDAC6 via PTEN/AKT/mTOR pathway, which might be a potential target for diagnostic and therapeutic in HNSCC.

摘要

作为一种内源性非编码小分子 RNA,microRNA(miRNA)在各种生理功能的调节中发挥着重要作用,但其对人头颈鳞状细胞癌(HNSCC)衰老的影响尚不清楚。本研究旨在探讨 miR-206 在 HNSCC 组织、相邻正常组织和细胞系中的作用,并探索其在 HNSCC 中的生物学功能。在我们的研究中,通过实时 qPCR 检测了 HNSCC 组织和相邻正常组织中 miR-206 的水平。通过 MTT 测定、集落形成和细胞周期测定检测 miR-206 对细胞增殖的影响。为了探讨 miR-206 对 HNSCC 细胞迁移和侵袭的影响,我们进行了划痕愈合实验和 Transwell 实验。设计了荧光素酶报告实验来鉴定 HDAC6 的 3'UTR 与 miR-206 之间的相互作用。通过 Western blot 测定信号通路相关蛋白的水平。通过实时 PCR 发现 miR-206 在 HNSCC 组织和细胞系中的表达明显降低。通过恢复 miR-206 的表达,减弱了 HNSCC 细胞的增殖、侵袭和迁移,并且细胞周期停滞在 S 期。进一步的研究表明,miR-206 通过靶向 PTEN/AKT/mTOR 通路抑制 HNSCC 细胞的增殖。总之,我们的研究结果表明,miR-206 通过靶向 HDAC6 并通过 PTEN/AKT/mTOR 通路在 HNSCC 进展中发挥关键作用,这可能是 HNSCC 诊断和治疗的潜在靶点。

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