关键词: circRNA biomarker circRNA-miRNA-gene interaction circular RNA computational approach gastric cancer

来  源:   DOI:10.3389/fmolb.2022.857320   PDF(Pubmed)

Abstract:
Gastric cancer (GC) is one of the most common malignant tumors and ranks third in cancer mortality globally. Although, a lot of advancements have been made in diagnosis and treatment of gastric cancer, there is still lack of ideal biomarker for the diagnosis and treatment of gastric cancer. Due to the poor prognosis, the survival rate is not improved much. Circular RNAs (circRNAs) are single-stranded RNAs with a covalently closed loop structure that don\'t have the 5\'-3\' polarity and a 3\' polyA tail. Because of their circular structure, circRNAs are more stable than linear RNAs. Previous studies have found that circRNAs are involved in several biological processes like cell cycle, proliferation, apoptosis, autophagy, migration and invasion in different cancers, and participate in some molecular mechanisms including sponging microRNAs (miRNAs), protein translation and binding to RNA-binding proteins. Several studies have reported that circRNAs play crucial role in the occurrence and development of different types of cancers. Although, some studies have reported several circRNAs in gastric cancer, more studies are needed in searching new biomarkers for gastric cancer diagnosis and treatment. Here, we investigated potential circRNA biomarkers for GC using next-generation sequencing (NGS) data collected from 5 paired GC samples. A total of 45,783 circRNAs were identified in all samples and among them 478 were differentially expressed (DE). The gene ontology (GO) analysis of the host genes of the DE circRNAs showed that some genes were enriched in several important biological processes, molecular functions and cellular components. The Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed that some host genes were enriched in several GC related pathways. The circRNA-miRNA-gene interaction network analysis showed that two circRNAs circCEACAM5 and circCOL1A1 were interacted with gastric cancer related miRNAs, and their host genes were also the important therapeutic and prognostic biomarkers for GC. The experimental results also validated that these two circRNAs were DE in GC compared to adjacent normal tissues. Overall, our findings suggest that these two circRNAs circCEACAM5 and circCOL1A1 might be the potential biomarkers for the diagnosis and treatment of GC.
摘要:
胃癌(GC)是最常见的恶性肿瘤之一,在全球癌症死亡率中排名第三。虽然,在胃癌的诊断和治疗方面取得了很多进步,目前仍缺乏理想的胃癌诊断和治疗的生物标志物。由于预后不良,存活率没有多大提高。环状RNA(circularRNAs)是具有共价闭环结构的单链RNA,不具有5'-3'极性和3'polyA尾巴。由于它们的圆形结构,circRNAs比线性RNAs更稳定。以前的研究发现circRNAs参与了几个生物过程,如细胞周期,扩散,凋亡,自噬,不同癌症的迁移和侵袭,并参与一些分子机制,包括海绵微小RNA(miRNA),蛋白质翻译和与RNA结合蛋白的结合。一些研究报道circRNAs在不同类型癌症的发生和发展中起着至关重要的作用。虽然,一些研究报道了几种circRNAs在胃癌中,在寻找胃癌诊断和治疗的新生物标志物方面还需要更多的研究。这里,我们使用从5个成对的GC样本中收集的下一代测序(NGS)数据,调查了GC的潜在circRNA生物标志物.在所有样品中鉴定了总共45,783个circRNAs,其中478个差异表达(DE)。对DEcircRNAs的宿主基因进行的基因本体论(GO)分析表明,一些基因在几个重要的生物过程中被富集,分子功能和细胞成分。京都基因和基因组百科全书(KEGG)途径分析显示,一些宿主基因富集在几种GC相关途径中。circRNA-miRNA-基因相互作用网络分析显示两个circCEACAM5和circCOL1A1与胃癌相关的miRNAs相互作用,它们的宿主基因也是GC的重要治疗和预后生物标志物。实验结果还验证了与邻近正常组织相比,这两种circRNAs在GC中是DE。总的来说,我们的研究结果表明,这两个circRNAcirCEACAM5和circCOL1A1可能是诊断和治疗GC的潜在生物标志物。
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