HIF1α/MALAT1/HOPX生物轴调控头颈部鳞癌侵袭转移的机制研究

侵袭转移是中晚期头颈部鳞癌预后不良的重要因素。乏氧条件下HIF1α促进头颈部鳞癌侵袭转移，其调控机制有待深入探究。课题组通过RNAseq筛选分析发现，乏氧下敲降HIF1α后抑癌基因HOPX表达升高，MALAT1表达降低；ChIPseq提示敲降MALAT1能显著改变HOPX基因位点H3K27me3富集水平；回复实验初步证实HIF1α通过MALAT1调控HOPX表达。由此我们提出“HIF1α/MALAT1/HOPX生物轴调控头颈部鳞癌侵袭转移”的研究假说，拟明确头颈部鳞癌组织中HIF1α、MALAT1和HOPX表达及与淋巴结转移、预后的关系；阐明HIF1α通过MALAT1调控HOPX表达的具体机制；体外、动物实验验证HIF1α/MALAT1/HOPX生物轴对头颈部鳞癌侵袭转移的影响。预期结果将揭示HIF1α/MALAT1/HOPX生物轴在头颈部鳞癌侵袭转移中的功能和机制，为临床诊疗提供新思路。

The major contributors to poor prognosis in patients with head and neck squamous cell carcinoma (HNSCC) are invasion and metastasis. Tumor hypoxia microenvironment could elevate HIF1α expression in HNSCC cells to promote invasion and metastasis, but the underlying mechanisms remain to be further explored. Through RNA sequencing, we found that HIF1α knockdown increased the mRNA of tumor suppressor HOPX but reduced LncRNA MALAT1 expression. Besides, the results of ChIP sequencing indicated that MALAT1 depletion significantly affected H3K27me3 level in the genomic region of HOPX. Rescue assay results indicated that HIF1α inhibited HOPX by regulating MALAT1. Here, we proposed the hypothesis that HIF1α/MALAT1/HOPX axis regulates invasion and metastasis in head and neck squamous cell carcinoma. In this research program, we aim to identify the relationship between HIF1α/MALAT1/HOPX expression and lymph node metastasis as well as prognosis in HNSCC, reveal the mechanism that HIF1α regulates MALAT1-mediated inhibition of HOPX to promote HNSCC invasion and metastasis, and explore the function and translational medicine prospect of HIF1α/MALAT1/HOPX axis in HNSCC invasion and metastasis in vitro and in vivo. Expected research results will elucidate the function and mechanism of HIF1α/MALAT1/HOPX axis in HNSCC invasion and metastasis, and provide new insight into clinical molecular diagnosis and anti-cancer strategies.