C-MYC诱导的长链非编码RNA SNHG20促进弥漫大B细胞淋巴瘤恶性进展的分子机制

原癌基因C-MYC高表达的弥漫大B细胞淋巴瘤（DLBCL）预后差，其通过转录激活靶基因发挥促癌功能，但C-MYC介导的新长链非编码RNA SNHG20对DLBCL进展的调控机制尚不明确。我们前期发现：DLBCL细胞中C-MYC调控SNHG20表达；DLBCL组织中SNHG20高表达提示治疗反应不良；干扰SNHG20抑制DLBCL细胞增殖并诱导凋亡，RON/β-catenin信号轴可能是其下游效应分子。因此，我们提出科学假说：C-MYC激活的SNHG20通过RON/β-catenin信号轴促进DLBCL恶性进展。本项目拟通过分子生物技术和功能学实验明确SNHG20在DLBCL中的临床意义；探索C-MYC对SNHG20表达的调控机制；揭示SNHG20促DLBCL恶性进展的分子机制；探讨干预SNHG20/RON信号轴对DLBCL恶性进展的影响。本项目为开发抗DLBCL靶向药物提供新的思路和依据。

Diffuse large B-cell lymphoma (DLBCL) with high expression of proto-oncogene C-MYC has a poor prognosis. C-MYC exerts a tumor promoting role by transcriptionally activating target genes. However, the regulatory mechanism whereby C-MYC-mediated novel long noncoding RNA SNHG20 on DLBCL progression is still unclear. We previously found that C-MYC regulated SNHG20 expression in DLBCL cells. High expression of SNHG20 in DLBCL tissues indicated a poor treatment response. SNHG20 knockdown inhibited DLBCL cell proliferation and induced apoptosis, and RON/β-catenin signal axis may be its downstream effectors. Therefore, we propose a scientific hypothesis: C-MYC activated SNHG20 promotes the malignant progression of DLBCL via RON/β-catenin signal axis. The molecular biotechnology and functional experiments will be carried out to confirm the clinical significance of SNHG20 in DLBCL, explore the regulatory mechanism of C-MYC on SNHG20 expression, reveal the molecular mechanism of SNHG20 in promoting the malignant progression of DLBCL and investigate the effect of interfering SNHG20/RON signal axis on the malignant progression of DLBCL. This project will provide a new idea and basis for the development of anti-DLBCL targeted drugs.