长链非编码 RNA (LINC00461)/miR-9 对霍奇金淋巴瘤的调控作用及机制

霍奇金淋巴瘤 (Hodgkin Lymphoma，HL) 来源于生发中心 B 细胞，是青年人中最常见的恶性肿瘤之一，其发病机制尚不清楚。因此，寻找防治肿瘤的有效措施，是目前 HL 治疗亟待解决的问题。长链非编码 RNA (lncRNA) 在肿瘤发生发展过程中发挥重要的调控作用，然而在 HL 中仍未见报道。我们基于前期工作提出假设：在 HL 中上调的 lncRNA (LINC00461) 作为 miR-9 的初始 miRNA (pri-miRNA) 促进其表达，导致其下游抑癌基因下调，从而促进 HL 细胞生长及肿瘤形成。本课题拟从在体和离体水平深入研究 (1) LINC00461 对 HL 细胞生长和肿瘤形成的作用；(2) 揭示 LINC00461 调控 HL 的分子机制；(3) LINC00461 是否可以成为肿瘤发生发展的预警因子及治疗靶点。本研究将为临床 HL 的防治提供新思路。

Hodgkin Lymphoma (HL) derived from germinal center B cells, is one of the most frequent lymphomas in adolescents and young people whose pathogenesis is still unknown. Understanding the putative mechanism of this disease is urgently needed to develop new therapeutic interventions for the treatment of HL. Long non-coding RNAs (lncRNAs) are emerging as critical regulators in the progression of multiple tumors. However, the pathophysiologic significance of them in HL remains elusive. We hypothesize that the elevated expression of lncRNA (LINC00461) enhances the expression of miR-9 via functioning as its pri-miRNA, which in turn repress the downstream anti-oncogenes expression and subsequently result in inhibition of HL tumor cell growth. In this project, in vivo and in vitro studies were performed to (1) indentify the potential role of LINC00461 in HL tumor growth；(2) unravel the molecular mechanism of LINC00461 in the regulation of HL；(3) determine whether the LINC00461 could represent a novel biomarker and therapeutic target for initiation and progression of HL. This project will provide us a new insight into clinical anti-HL treatment.