长链非编码RNA-LSINCT5在胃癌中的生物学功能及机制研究

Gastric cancer (GC) is one of high morbidity and mortality of malignant tumor in China. About 4%-9% of the genome are actively transcribed into long non-coding RNAs (lncRNAs), a newly discovered class of ncRNAs that are longer than 200 nucleotides. Changes in the expression levels of lncRNAs have been increasingly reported in a variety of cancer types, suggesting a connection between lncRNAs and carcinogenesis and the potential of lncRNAs as a novel target for cancer diagnostics and therapeutics. By using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis, we found that long stress-induced noncoding transcript 5 (LSINCT5) was overexpressed in GC tissues compared with adjacent normal tissues. Potential relationship between tumor LSINCT5 levels and some clinicopathological features was found, and high LSINCT5 expression had a significantly poorer prognosis than those with low LSINCT5 expression. In addition, overexpression of LSINCT5 inhibits growth of gastric cancer in vitro. By using bioinformatics analysis combined with cellular functional experiments, we found the potential target molecules of LSINCT5, including protein-coding genes and miRNAs. The actual mechanism needs to be further explored. Based on these results, we plan to investigate the biological function of LSINCT5 in the onset and development of GC by means of gene cloning, RNA interference, and viral infection in vitro, as well as animal models; clarify the downstream regulative mechanism related to its biological function by using molecular biology combined with cell biology. This study will offer important theoretical significance and clinical value in screening molecular markers for prognosis and targeted therapy.

胃癌（GC）是我国发病率和死亡率极高的恶性肿瘤，至今仍未能充分阐明其癌变机制并建立有效的诊治手段。人类基因组序列中有4%-9%产生的转录本是长链非编码RNA，它们与众多肿瘤的发生、转移有关。我们前期发现应激诱导长非编码转录本5（LSINCT5）在胃癌组织中异常表达，且LSINCT5相对高表达患者预后不良。LSINCT5可显著促进胃癌细胞增殖，但其具体生物学功能有待深入研究。生物信息学分析结合生物学实验，我们初步确立了LSINCT5的潜在靶分子，需验证具体调控机制。拟通过①调控LSINCT5在体外细胞、活体动物的表达水平研究其在GC中的生物学功能；②应用分子细胞生物学等实验阐明LSINCT5在胃癌中的下游调控机制，揭示 LSINCT5-靶分子调节通路参与胃癌发生和恶性转归的生物学过程；③探索相关分子的临床病理相关性和预后预测意义。本项目对于GC预后评估及靶向治疗具有重要的理论意义和临床价值。

项目的背景：胃癌是我国发病率和死亡率极高的恶性肿瘤，至今仍未能充分阐明其癌变机制并建立有效的诊治手段。人类基因组序列中有4%-9%产生的转录本是长链非编码RNA，它们与众多肿瘤的发生、转移有关。我们前期发现应激诱导长非编码转录本5（LSINCT5）在胃癌组织中异常表达，且LSINCT5相对高表达患者预后不良。LSINCT5可显著促进胃癌细胞增殖，但其具体生物学功能有待深入研究。生物信息学分析结合生物学实验，我们初步确立了LSINCT5的潜在靶分子，需验证具体调控机制。.主要研究内容：拟通过①调控LSINCT5的表达水平研究其在GC中的生物学功能；②应用分子细胞生物学等实验阐明LSINCT5在胃癌中的下游调控机制，揭示LSINCT5-靶分子调节通路参与胃癌发生和恶性转归的生物学过程；③探索相关分子的临床病理相关性和预后预测意义。.研究工作主要成果：.1. LSINCT5可影响胃癌细胞迁移和侵袭能力。.2. 转录因子E2F1调控LSINCT5在胃癌细胞中的表达。.3. LSINCT5通过调节EMT促进胃癌细胞的迁移和侵袭。.4. LSINCT5高表达与肿瘤大小、浸润深度、淋巴结转移及肿瘤TNM分期显著相关，LSINCT5表达水平高的患者预后不良。.科学意义：本课题为LSINCT5在胃癌中的作用机制提供基础实验依据，具有潜在的临床应用价值，有助于筛选关键的肿瘤治疗靶标和预后评估分子标志物。