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长链非编码 RNA MIR31HG 通过促进细胞周期进程来靶向 HIF1A 和 P21,从而促进头颈部癌细胞的增殖和肿瘤发生。

LncRNA MIR31HG targets HIF1A and P21 to facilitate head and neck cancer cell proliferation and tumorigenesis by promoting cell-cycle progression.

机构信息

Department of Otolaryngology Head and Neck Surgery, Beijing Tongren Hospital, Capital Medical University, Beijing, 100730, China.

Key Laboratory of Otolaryngology Head and Neck Surgery (Ministry of Education of China), Beijing Institute of Otolaryngology, Beijing, 100005, China.

出版信息

Mol Cancer. 2018 Nov 20;17(1):162. doi: 10.1186/s12943-018-0916-8.

DOI:10.1186/s12943-018-0916-8
PMID:30458787
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6247607/
Abstract

LncRNAs are involved in the initiation and progression of cancer. However, the molecular mechanism and diverse clinical prognosis of MIR31HG in head and neck squamous cell carcinoma (HNSCC) are still unclear. Our previous microarray analysis showed that lncRNA MIR31HG interacted with HIF1A may play an oncogenic role in laryngeal squamous cell cancer (LSCC). To determine whether lncRNA MIR31HG served as a poor prognosis factor and targeted HIF1A to facilitate cell proliferation and tumorigenesis in human HNSCC, we found MIR31HG and HIF1A were overexpressed in LSCC, MIR31HG overexpression or co-expression of HIF1A-positive and p21-negative could serve as a poor prognostic factor for LSCC patients. We further confirmed that MIR31HG promoted cell proliferation, cell cycle progression, and inhibited cell apoptosis in vitro and in vivo. The ingenuity pathway analysis and Western blot indicated that MIR31HG regulated cell cycle progression via HIF1A and p21 in HNSCC. The current results provide evidences for the role of MIR31HG in promoting HNSCC progression and identify MIR31HG as a prognostic biomarker and putative therapeutic target in HNSCC.

摘要

长链非编码 RNA 参与癌症的发生和发展。然而,MIR31HG 在头颈部鳞状细胞癌(HNSCC)中的分子机制和不同的临床预后仍不清楚。我们之前的基因芯片分析表明,lncRNA MIR31HG 与 HIF1A 相互作用可能在喉鳞状细胞癌(LSCC)中发挥致癌作用。为了确定 lncRNA MIR31HG 是否作为不良预后因素,并靶向 HIF1A 促进人 HNSCC 中的细胞增殖和肿瘤发生,我们发现 MIR31HG 和 HIF1A 在 LSCC 中过度表达,MIR31HG 过表达或与 HIF1A 阳性和 p21 阴性共表达可作为 LSCC 患者的不良预后因素。我们进一步证实,MIR31HG 促进了体外和体内的细胞增殖、细胞周期进程,并抑制了细胞凋亡。通过 IPA 和 Western blot 分析表明,MIR31HG 通过 HIF1A 和 p21 调节 HNSCC 中的细胞周期进程。目前的研究结果为 MIR31HG 在促进 HNSCC 进展中的作用提供了证据,并确定 MIR31HG 是 HNSCC 的预后生物标志物和潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f9/6247607/b7ba8aaf6498/12943_2018_916_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f9/6247607/a9e9aa987bbf/12943_2018_916_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f9/6247607/707cc62cefc5/12943_2018_916_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f9/6247607/b7ba8aaf6498/12943_2018_916_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f9/6247607/a9e9aa987bbf/12943_2018_916_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f9/6247607/707cc62cefc5/12943_2018_916_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/91f9/6247607/b7ba8aaf6498/12943_2018_916_Fig3_HTML.jpg

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