lncRNA CCAL作为ceRNA调控MAPK促进胃癌进展的机制研究

It is of great significance to explore the genes related to the pathogenesis of gastric cancer and to use them as ideal biomarkers for clinical diagnosis. Recent studies have shown that long non-coding RNA (lncRNA) as a competitive endogenous RNA (ceRNA) plays an important regulatory role in the development of gastric cancer. We used gene chips to screen out the high expression lncRNA CCAL in gastric cancer. Bioinformatics predicts miR-149-5p is the target gene of CCAL, and MAPK is the target protein of miR-149-5p. The pre-experiments have confirmed there were some correlations between the expression of CCAL, miR-149-5p and MAPK, suggesting that CCAL can act as a ceRNA to regulate miR-149-5p function and activate MAPK in gastric cancer progression. Therefore, we will study the mechanism of CCAL-miR-149-5p-MAPK regulatory network based on ceRNA model in the progression of gastric cancer at the cellular and animal level by using luciferase assay and RNA pulldown test. Meanwhile, the clinical value of CCAL as a potential diagnostic marker for gastric cancer will be explored. This study can shed some light on the pathogenesis of gastric cancer and also provide a new molecular target for clinical diagnosis and treatment.

探寻与胃癌发病机制相关的基因，并将其作为理想生物标志物用于临床诊断，具有重要的研究价值。最近研究发现，长链非编码RNA（lncRNA）作为竞争性内源RNA（ceRNA）在胃癌发生发展过程中起着重要的调控作用。我们前期通过基因芯片筛选出胃癌中高表达的lncRNA CCAL；生物信息学预测其为miR-149-5p的靶基因，MAPK为miR-149-5p的靶蛋白；预实验已证实CCAL、miR-149-5p、MAPK三者表达具有相关性；推测CCAL可作为ceRNA调控miR-149-5p的功能，活化MAPK促进胃癌进展。本课题拟运用荧光素酶试验、RNA拉下试验等技术在细胞及动物水平探讨基于ceRNA模式的CCAL-miR-149-5p-MAPK调控网络在胃癌的发生、发展中的作用机制；同时探讨血浆CCAL作为胃癌潜在诊断标志物的临床应用价值。本研究可为胃癌发病机制研究及临床诊疗提供新思路和新靶标。

胃癌是中国最常见的肿瘤之一，发病率在恶性肿瘤中排名第四。探寻与胃癌发病机制相关的基因，并将其作为理想生物标志物用于临床诊断，具有重要的研究价值。近年来应用于临床的无创、简便、灵敏的检测方法检测血清或血浆肿瘤标志物受到越来越多的重视。长链非编码RNA（lncRNA）可作为竞争性内源RNA（ceRNA）发挥重要的转录后调控作用，调节胃癌发生发展过程。本课题筛选出胃组织中高表达的lncRNA CCAL；生物信息学预测并验证其为miR-149-5p的靶基因，发挥内源性miR-149-5p 海绵的功能，体内外功能实验证实其可调控胃癌细胞增殖、凋亡、侵袭、转移等恶性生物学行为。RT-PCR检测CCAL在胃癌组织及血浆中表达水平，CCAL在胃癌患者组织及血浆中明显增高，与临床TNM分期及Lauren 分型显著相关，与胃癌患者的年龄、性别、肿瘤大小、分化程度、淋巴结转移无显著相关。建立了血浆CCAL诊断胃癌的ROC曲线，显示较高的灵敏度和特异度，提示血浆CCAL作为胃癌潜在诊断标志物具有较好的临床应用价值。