长链非编码RNA-AF085943结合蛋白CELF1对弥漫性大B细胞淋巴瘤发生发展调节作用的研究

弥漫大B细胞淋巴瘤（DLBCL）的发病机制至今仍未完全阐述；长链非编码RNA（lncRNA）在肿瘤发生发展特别是基因调控中发挥关键作用。本课题通过前期DLBCL组织芯片分析和验证，获得对DLBCL具有重要作用的全新lncRNA AF085943,对AF085943在大量临床标本中的表达及相关性分析提示其是DLBCL诊断与预后的新的重要标志物。进一步深入研究发现其相互作用的蛋白CELF1，AF085943通过和CELF1互相作用调控下游转录因子FAM3C表达，而FAM3C又可转录活化AF085943。基于此，本课题拟明确AF085943/CELF1/FAM3C正反馈通路在DLBCL中的作用，进一步探究AF085943和CELF1相互作用对DLBCL发生发展的新调控机制，通过体内、体外实验观察AF085943对DLBCL的生物学意义，证实其作为DLBCL诊断与预后标志物，以及治疗靶点的可行性。

Until now, the pathophysiological mechanisms contributing to diffuse large B-cell lymphoma (DLBCL) still remains largely elusive. Emerging evidences demonstrated that long noncoding RNAs (lncRNAs) play important roles in cancer-related genes regulations. From our previous DLBCL microarrays we first found a novel lncRNA AF085943 that was responsible for DLBCL carcinogenesis. Aberrant expression of AF085943 in a large cohort of specimens implicated that it could be a critical diagnostic and prognostic biomarker for DLBCL. We showed a protein CELF1, that was associated with AF085943. With CELF1, AF085943 might regulate the expression of transcription factor FAM3C. Conversely, FAM3C could elevate the levels of AF085943. Based on the above, we planned to explored the role of AF085943/CELF1/FAM3C loop in DLBCL.