假基因LncRNASUZ12p促进非小细胞肺癌转移的分子机制研究

Lung cancer is one of the most common malignant tumors in the world, Elucidating the molecular mechanism of metastasis is a key scientific problems to be solved in lung cancer. Our previous study established highly invasive (SPC-A-1sci)and weakly invasive cell sublines(SPC-A-1),we revealed that pseudogene LncRNASUZ12p might be a new tumor-promotor for lung cancer metastasis by comparing the global lncRNA microarray of SPC-A-1sci and SPC-A-1 cells and experimental verification. Our preliminary experiments demonstrated that LncRNASUZ12p regulated the transcription of host gene SUZ12,and directly binded RB1 protein. We will carry out a in-depth study of the role of LncRNASUZ12p in lung cancer metastasis on a cellular, molecular or overall level. Moreover, to further determine how LncRNASUZ12p contributes to the metastasis of lung cancer, we will search for the potential regulatory targets by RNA pull down、CHIP、RIP、RNA microarray, quantitative proteomics and so on, and examine the relationship between LncRNASUZ12p and the potential regulatory targets by analysing the large of patient samples. We will further realize the molecular mechanism of LncRNASUZ12p in lung cancer metastasis , and provide a new idea for the treatment of lung cancer metastasis.

肺癌是世界上最常见的恶性肿瘤，阐明其转移的分子机制是肺癌研究领域亟需解决的关键科学问题之一。本课题组前期以自建的肺癌高、低转移细胞为研究对象，采用LncRNA表达谱检测、生物信息学分析和实验验证，初步证实假基因LncRNASUZ12p转录调控宿主基因SUZ12的表达，并直接结合RB1蛋白，提示假基因LncRNASUZ12p可能是非小细胞肺癌新的转移促进基因。本项目拟在分子水平、细胞水平和整体水平深入研究假基因LncRNASUZ12p在肺癌转移过程中的作用，同时采用RNA pull down、RNA测序、CHIP、RIP及蛋白质谱分析等技术，寻找相关的调控蛋白及其参与的信号通路，进一步阐明假基因LncRNASUZ12p影响肺癌转移的分子机制，最终使用大样本临床标本进行相关性验证和分析。通过对假基因LncRNASUZ12p在肺癌转移过程中功能及分子机制研究可能为肺癌转移的临床治疗提供参考依据。

肺癌是世界上最常见的恶性肿瘤，阐明其转移的分子机制是肺癌研究领域亟需解决的关键 科学问题之一。本课题组前期以自建的肺癌高、低转移细胞为研究对象，采用LncRNA表达谱检测、生物信息学分析和实验验证，证实SUZ12P 和 SUZ12 的高表达水平与 NSCLC 患者的不良预后显着相关，表明SUZ12P可能是NSCLC中的潜在致癌基因。表明SUZ12P是一种顺式作用lncRNA，其SUZ12P的NOL区域在调节SUZ12表达中起关键作用。结果表明 SUZ12P 与 NSCLC 细胞中的 RB1 特异性结合。SUZ12P 通过抑制 PP1c 和 RB1 之间的结合来影响 RB1-Ser795 和 RB1-Ser807 磷酸化。将稳定的 CRISPR-SUZ12P-gRNA 细胞皮下注射到裸鼠体，与对照组相比，CRISPR-SUZ12P-gRNA 组中肿瘤的体积和重量均受到显着抑制。SUZ12P 与 NSCLC 细胞中的 RB1 特异性结合。SUZ12P 通过抑制 PP1c 和 RB1 之间的结合来影响 RB1-Ser795 和 RB1-Ser807 磷酸化。总之，这些发现表明，SUZ12P-RB1 轴可能是 NSCLC 的潜在治疗靶点。通过对假基因LncRNASUZ12p在肺癌转移过程中功能及分子机制研究可能为肺癌转移的临床治疗提供参考依据。