Department of Gastroenterology, Affiliated Hospital of Weifang Medical University, Weifang, P.R. China.
Eur Rev Med Pharmacol Sci. 2019 Jul;23(14):6170-6178. doi: 10.26355/eurrev_201907_18430.
Cardia cancer is a common type of gastric cancer. Most clinical prevention and prognosis focus on surgical resection, but the efficacy is not satisfactory. Studying the molecular mechanism of pathogenesis of cardia cancer helps us intervene in prognosis and treatment.
a total of 134 normal cases related to cardia cancer and 62 cases of cardia cancer samples from the Gene Expression Omnibus (GEO) database were collected. A series of bioinformatics analyses, including differential gene analysis, co-expression analysis, enrichment analysis, regulator prediction, and (Protein-protein interaction) PPI analysis validation were performed.
Differential analysis highlighted 10882 differential genes (p<0.05). Weighted gene co-expression network analysis indicated 6 functional disorder modules. TMOD1, JAM2, SPARC, ST18, NOS1 were key genes of each module. Enrichment analysis showed the dysfunctional module genes were mainly related to the proteinaceous extracellular matrix and neuroactive ligand-receptor interaction. Pivotal analysis of ncRNA demonstrated miR-17-5p significantly regulates modular genes including m1, m3, and m5. Target genes were backtracked according to the key regulators. Then, the Module_target gene_ncRNA interaction network diagram was constructed. The network shows m1 has the strongest regulation effect in the network. PPI showed that the core gene TMOD1 (Tropomodulin1) of m1 was at TOP10 in the algorithm. In other words, PPI indicated the importance of TMOD1 in the interaction network.
We believe that targeted regulation of miR-17-5p on TMOD1 gene affects the neuroactive ligand-receptor interaction pathway, and it promotes proliferation and apoptosis of cardia cancer cells.
贲门癌是一种常见的胃癌类型。大多数临床预防和预后都集中在手术切除上，但疗效并不理想。研究贲门癌发病机制的分子机制有助于我们干预预后和治疗。
共收集了 134 例贲门癌相关的正常病例和 62 例贲门癌组织样本，来源于基因表达综合数据库（GEO）。对其进行了一系列的生物信息学分析，包括差异基因分析、共表达分析、富集分析、调控预测和（蛋白质-蛋白质相互作用）PPI 分析验证。
差异分析显示了 10882 个差异基因（p<0.05）。加权基因共表达网络分析表明存在 6 个功能失调模块。TMOD1、JAM2、SPARC、ST18、NOS1 是每个模块的关键基因。富集分析显示，功能失调模块基因主要与蛋白质细胞外基质和神经活性配体-受体相互作用有关。ncRNA 的关键分析表明，miR-17-5p 显著调节模块基因，包括 m1、m3 和 m5。根据关键调控因子对靶基因进行回溯。然后构建了模块-靶基因-ncRNA 相互作用网络图。该网络显示 m1 具有网络中最强的调节作用。PPI 表明 m1 中核心基因 TMOD1（Tropomodulin1）在算法中排名前十。换句话说，PPI 表明 TMOD1 在相互作用网络中的重要性。
我们认为，miR-17-5p 对 TMOD1 基因的靶向调节影响神经活性配体-受体相互作用途径，促进贲门癌细胞的增殖和凋亡。
