不同海拔地区藏族胃癌患者miRNA的初步筛选

目的 筛选不同海拔地区生活的藏族患者的胃癌组织微小RNA(miRNA)差异表达,探讨高原地区外环境缺氧是否参与调控肿瘤的发生、侵袭和转移等.方法 选择5对不同海拔地区生活的藏族胃癌患者作为研究对象(其中海拔﹥3500 m者5例,海拔﹤2450 m者5例),对胃癌组织及其配对癌旁组织进行miRNA芯片检测,分析差异miRNA,查询差异miRNA-靶基因,预测的靶基因应用DAVID数据库进行功能富集分析(GO分析)和pathway富集分析.结果 在5对不同海拔地区生活的藏族胃癌患者的胃癌组织及其配对癌旁组织中找出16个差异表达的miRNA,在海拔﹥3500 m组均上调,仅有hsa-miR-1260b、hsa-miR-130b-3p、hsa-miR-3648、hsa-miR-4284预测到验证的靶基因,其中hsa-miR-1260b预测118个,hsa-miR-130b-3p预测151个.这些靶基因富集在细胞增殖、基因表达调控、转录调控、细胞周期、细胞内信号传导等生物学过程和功能上;pathway富集到癌症通路上.结论 在高原藏族胃癌患者的肿瘤生长、侵袭、转移及肿瘤耐药等过程中,hsa-miR-1260b、hsa-miR-130b-3p可能发挥着重要的作用.

Preliminary screening of microRNA(miRNA)in Tibetan gastric cancer patients at different altitudes

Objective To investigate the differential expression of miRNA in gastric cancer tissues of Tibetans living in different altitudes,and to explore whether the high-altitude hypoxic environment is involved with the development,in-vasion,and metastasis of gastric cancer.Method 5 pairs of Tibetan gastric cancer patients(5 living above 3500 meters from sea level and 5 living below 2450 meters)were included in this study,and their gastric cancer tissues and matched adjacent normal tissues were sampled for miRNA microarray assay to detect differentially expressed miRNA.Predicted target genes of the differentially expressed miRNA subsequently underwent Gene Ontology(GO)analysis and pathway enrichment analysis using the DAVID database. Result 16 miRNA were found to be differentially expressed between gastric cancer tissues and adjacent normal tissues of these 5 pairs of subjects living at various altitudes,and all of them were upregulated in patients living above 3500 meters,and the predicted genes of only hsa-miR-1260b,hsa-miR-130b-3p,hsa-miR-3648,hsa-miR-4284 were verified,wherein,118 genes were predicted to be regulated by hsa-miR-1260b, and 151 by hsa-miR-130b-3p.These target genes were enriched in cell proliferation,gene expression regulation,transcrip-tional regulation,cell cycle,and intracellular signaling;pathway analysis showed enrichment in the cancer pathways.Con-clusion hsa-miR-1260b and hsa-miR-130b-3p may play an important role in the growth,invasion,metastasis,and drug resistance of gastric cancer in Tibetans,and further verification is required.