LncRNA HCLS1-1/hsa-miR-107/HOXC10轴调控EMT促进口腔鳞癌侵袭转移的机制研究

淋巴结转移是口腔鳞癌患者的首要不良预后因素和诊治难点。申请人前期研究发现HOXC10通过增强肿瘤细胞上皮间质转化（EMT）促进口腔鳞癌侵袭转移，但调控HOXC10的分子机制不明确。本项目前期利用转录组学和生物信息学研究发现并初步证实lncRNA HCLS1-1/hsa-miR-107轴可以调控HOXC10表达。结合国内外已有研究，申请人提出假说：lncRNA HCLS1-1通过ceRNA机制竞争性结合hsa-miR-107，阻断hsa-miR-107对HOXC10的抑制，增强肿瘤细胞EMT促进口腔鳞癌侵袭转移。本项目拟利用肿瘤组织样本评价lncRNA HCLS1-1、hsa-miR-107和HOXC10在诊断和预后判断的作用；细胞学水平和动物模型水平揭示lncRNA HCLS1-1的生物学功能；分子水平阐明lncRNA HCLS1-1/hsa-miR-107调控HOXC10的具体分子机制。

Lymph node metastasis is the primary factor affecting the prognosis of oral squamous cell carcinoma (OSCC) and the difficulty in diagnosis and treatment. Our previous study found that HOXC10 promoted the invasion and metastasis of OSCC by enhancing epithelial-mesenchymal transformation (EMT) of tumor cells, but the mechanism of HOXC10 regulation is still unclear. In the early stage of this project, transcriptome and bioinformatics studies were used to find and preliminarily confirm that the lncRNA HCLS1-1/ hsa-miR-107 pathway can regulate the expression of HOXC10. Combined with existing studies at home and abroad, we proposed the following hypothesis: lncRNA HCLS1-1 competitively binds hsa-miR-107 through the ceRNA mechanism, blocking the inhibition of hsa-miR-107 on HOXC10, and enhances tumor cell EMT to promote the invasion and metastasis of OSCC. We evaluate the expressional correlation and clinical significance between lncRNA HCLS1-1, hsa-miR-107 and HOXC10 by utilizing the OSCC tissue bank; We reveal the function of lncRNA HCLS1-1 in OSCC in cytologically and in animal model; We reveal the mutual regulation mechanism of lncRNA HCLS1-1/ hsa-miR-107 regulates HOXC10.