EHMT1/miR-602协同调控MAL基因影响口腔鳞癌转移的机制

An miRNA array of miRNomes in human no-metastasis and metastsis oral squamous cell carcinoma (OSCC) tissues was carried out. miR-602 was found to be expressed at higher levels in metastasis OSCC, and which play the function of promoting cancer cell metastasis. Computational prediction results indicated that miR-602 directly targeted Myelin and lymphocyte-associated protein gene (MAL). Ectopic expression of miR-602 in OSCC cancer cells suppressed MAL and promoted cell invasion. Our previous studies have confirmed the MAL gene in OSCC is significantly correlated with metastasis, which strongly suggest miR-602 is an important molecular basis of OSCC metastasis. We then predicted by bioinformatics that miR-602 located in twentieth intron region of EHMT1, and its host gene EHMT1 may catalyzes H3K9 methylation at promoters of MAL genes. This project mainly research at the metastasis of OSCC. Collectively, our hypothesis proposed that miR-602 may function synergistically with EHMT1 to enhance OSCC cancer cell motility and invasion by regulated the expression of MAL, which preliminary elucidate the metastasis mechanisms of OSCC, and as a potential therapeutic target in clinical application.

本课题通过miRNA表达谱芯片检测淋巴结转移与无淋巴结转移口腔鳞癌组织，发现并在临床样本中证实miR-602在转移性口腔鳞癌中异常高表达，证实了miR-602可以促进口腔鳞癌的侵袭与迁移能力；通过生物信息学分析发现：miR-602的癌基因功能是通过调控其靶基因MAL的表达来实现的。而我们前期研究已证实MAL基因在口腔鳞癌中与鳞癌转移明显相关，强烈提示miR-602高表达是口腔鳞癌发生转移的一个重要分子基础。结合生物信息学手段，我们观察到内含子miR-602位于组蛋白甲基转移酶EHMT1内含子区域，EHMT1可能通过对组蛋白的甲基化修饰在转录水平调控MAL基因的表达。本研究以口腔鳞癌为研究对象，有望初步阐明甲基转移酶基因EHMT1与miR-602协同调控MAL基因的作用机制及对肿瘤转移的影响，部分阐明该类恶性肿瘤转移机制以及为临床应用研究提供潜在治疗靶点。

本课题通过miRNA表达谱芯片检测淋巴结转移与无淋巴结转移口腔鳞癌组织，发现并在临床样本中证实miR-602在转移性口腔鳞癌中异常高表达，证实了miR-602可以促进口腔鳞癌的侵袭与迁移能力；通过生物信息学分析发现：miR-602的癌基因功能是通过调控其靶基因MAL的表达来实现的。而我们前期研究已证实MAL基因在口腔鳞癌中与鳞癌转移明显相关，强烈提示miR-602高表达是口腔鳞癌发生转移的一个重要分子基础。结合生物信息学手段，我们观察到内含子miR-602位于组蛋白甲基转移酶EHMT1内含子区域，EHMT1可能通过对组蛋白的甲基化修饰在转录水平调控MAL基因的表达。本研究以口腔鳞癌为研究对象，有望初步阐明甲基转移酶基因EHMT1与miR-602协同调控MAL基因的作用机制及对肿瘤转移的影响，部分阐明该类恶性肿瘤转移机制以及为临床应用研究提供潜在治疗靶点。