PDF(Pubmed)
Abstract：
Gastric cancer (GC) is one of the most prominent malignancies that originate in the epithelial cells of the gastric mucosa and is one of the main causes of cancer-related mortality worldwide. New circulating biomarkers of exosomal RNA might have great potential for non-invasive early prognosis of GC. Sijunzi Decoction (SJZD) is a typical representative formula of the method of benefiting Qi and strengthening the spleen in Traditional Chinese Medicine (TCM). However, the effects and mechanism of SJZD in treating GC remain unclear. This study looked for biomarkers of exosomal RNA for early prognosis of GC, and explored the mechanism of SJZD in treating GC. A gastric cancer model with spleen deficiency syndrome was established in nude mice, and the curative effects of SJZD were investigated. Differentially expressed miRNAs in plasma and saliva exosomes were sequenced and analyzed. Potential target genes of these miRNAs were predicted and applied for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway enrichment annotation. Overlapping miRNAs in saliva and plasma samples were analyzed, and qRT-PCR was performed for verification. miR-151a-3p was selected, and qRT-PCR further determined that miR-151a-3p was downregulated in saliva and plasma exosomes from the SJZD group. The intersected miR-151a-3p target genes were predicted and enriched in the extrinsic apoptotic signaling pathways. SJZD significantly ameliorates gastric cancer with spleen deficiency syndrome in mouse models, and exosomal miRNAs, particularly miR-151-3p, might be modulated by SJZD in plasma and saliva. The exosomal miR-151-3p in saliva may serve as a non-invasive potential marker for gastric cancer diagnosis and prognosis.
摘要：
胃癌（GC）是起源于胃粘膜上皮细胞的最突出的恶性肿瘤之一，是全球癌症相关死亡的主要原因之一。新的外泌体RNA循环生物标志物可能对GC的非侵入性早期预后具有巨大潜力。四君子汤(SJZD)是中医益气健脾法的典型代表方。然而,SJZD治疗GC的作用和机制尚不清楚。本研究寻找外泌体RNA的生物标志物对GC的早期预后，并探讨了SJZD治疗GC的机理。建立胃癌裸鼠脾虚证模型,并对SJZD的疗效进行了研究。对血浆和唾液外泌体中差异表达的miRNA进行测序和分析。这些miRNA的潜在靶基因被预测并应用于基因本体论(GO)和京都基因和基因组百科全书(KEGG)信号通路富集注释。分析了唾液和血浆样品中重叠的miRNA,和qRT-PCR进行验证。选择miR-151a-3p，qRT-PCR进一步确定miR-151a-3p在SJZD组的唾液和血浆外泌体中下调。预测交叉的miR-151a-3p靶基因并富集在外源性凋亡信号通路中。SJZD在小鼠模型中显著改善胃癌脾虚证,和外泌体miRNA，特别是miR-151-3p，可能由血浆和唾液中的SJZD调节。唾液中的外泌体miR-151-3p可作为胃癌诊断和预后的非侵入性潜在标志物。
