LncRNA MIR31HG targets HIF1A and P21 to facilitate head and neck cancer cell proliferation and tumorigenesis by promoting cell-cycle progression
LncRNA MIR31HG targets HIF1A and P21 to facilitate head and neck cancer cell proliferation and tumorigenesis by promoting cell-cycle progression
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LncRNA MIR31HG 靶向 HIF1A 和 P21，通过促进细胞周期进程来促进头颈癌细胞增殖和肿瘤发生
DOI：
10.1186/s12943-018-0916-8
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发表时间：
2018-11-20
期刊：
影响因子：
37.3
通讯作者：
Fang, Jugao
中科院分区：
文献类型：
--
作者：
Wang, Ru;Ma, Zhihong;Fang, Jugao
LncRNAs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尚不清楚。我们先前的微阵列分析表明，LncRNA MIR31HG与HIF1a相互作用可能在喉鳞状细胞癌(LSCC)中起致癌作用。为探讨lncRNA MIR31HG是否可作为喉癌预后不良因素，靶向HIF1a是否可促进HNSCC的增殖和肿瘤发生，我们发现MIR31HG和HIF1a在喉癌中均有过表达，MIR31HG过表达或HIF1a阳性和p21阴性共同表达可能是喉癌患者预后不良的因素。我们进一步证实了MIR31HG在体内外促进细胞增殖、细胞周期进程、抑制细胞凋亡。独创性通路分析和Western印迹分析表明，MIR31HG通过HIF1a和p21调控HNSCC的细胞周期进程。目前的结果为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的治疗靶点。
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.