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首页> 外文期刊>Molecular and Cellular Biochemistry: An International Journal for Chemical Biology >Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1-VEGF signaling pathway
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Role of miRNA-210, miRNA-21 and miRNA-126 as diagnostic biomarkers in colorectal carcinoma: impact of HIF-1-VEGF signaling pathway

机译：miRNA-210，miRNA-21和miRNA-126作为结直肠癌诊断生物标志物的作用：HIF-1-VEGF信号通路的影响

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Colorectal cancer (CRC) is a major cause of death worldwide. Novel non-invasive, high diagnostic value screening test is urgently needed to improve survival rate, treatment and prognosis. Stable, small, circulating microRNA (miRNA) offers unique opportunities for the early diagnosis of several diseases. It acts as tumor oncogenes or suppressors and involve in cell death, survival, and metastasis. Communication between miRNA and carcinogenesis is critical but it still not clear and needs further investigation. The aim of our study is to evaluate the role of miR-210, miR-21, miR-126, as non-invasive diagnostic biomarkers for screening, early detection of CRC, studying their correlation with prognostic variables, and clarifying the roles of miRNAs on HIF-1-VEGF signaling pathway. The expression of miR-210, miR-21 and miR-126 was performed using qRT-PCR in adenocarcinoma (no=35), adenomas (no=51), and neoplasm free controls (no=101). Serum levels of VEGF and HIF-1 was determined by ELISA Kit. The results show that the expression of miR-210, miR-21, VEGF, HIF-1 was significantly up-regulated while that miRNA-126 was down-regulated in both adenocarcinoma and adenomas compared with controls (p<0.001 for each). No significant difference was noted comparing patients with adenocarcinoma and adenomas. The three miRNAs correlated with VEGF, HIF-. The miR-210 and miR-21 associated with TNM classification and clinical staging of adenocarcinoma (p<0.001) and they show high diagnostic value with sensitivity and specificity 88.6%, 90.1% and 91.4%, 95.0% respectively. Our study revealed that circulating miR-210, miR-21 were up-regulated while miR-126 was down-regulated in CRC and adenomas patients, they all correlated with TNM staging and they had high diagnostic value. HIF-1 VEGF signaling pathways regulated by miRNAs played a role in colon cancer initiation. To the best of our knowledge, this is the first study of this miRNAs panel in CRC in our community. These data suggested that these biomarkers could be a potential novel, non-invasive marker for early diagnosis, screening and predicting prognosis of CRC. Understanding the molecular functions by which miRNAs affect cancer and understanding its roles in modulating the signaling output of VEGF might be fruitful in reducing the incidence and slowing the progression of this dark malignancy.
机译：结肠直肠癌（CRC）是全世界死亡的主要原因。迫切需要新型无侵入性，高诊断值筛查试验，以提高存活率，治疗和预后。稳定，小，循环的microRNA（miRNA）为早期诊断出几种疾病提供独特的机会。它充当肿瘤癌肠或抑制剂，涉及细胞死亡，存活和转移。 miRNA和致癌物之间的沟通至关重要，但它仍然不清楚并需要进一步调查。我们的研究目的是评估miR-210，miR-21，miR-126的作用，作为筛选，早期检测CRC的非侵入性诊断生物标志物，研究其与预后变量的相关性，并阐明miRNA的作用关于HIF-1-VEGF信号通路。使用QRT-PCR在腺癌（NO = 35），腺瘤（NO = 51）和肿瘤自由对照（NO = 101）中进行MIR-210，miR-21和miR-126的表达。通过ELISA试剂盒测定VEGF和HIF-1的血清水平。结果表明，MiR-210，miR-21，VEGF，HIF-1的表达显着上调，而MiRNA-126与对照相比，miRNA-126在腺癌和腺瘤两者中受到了下调（每次P <0.001）。对腺癌和腺瘤的患者进行了注意的患者没有显着差异。三个miRNA与VEGF，HIF-相关。与TNM分类和腺癌的临床分期相关的miR-210和miR-21（P <0.001），它们显示出高敏感性和特异性的高诊断值88.6％，90.1％和91.4％，95.0％。我们的研究表明，循环miR-​​210，miR-21上调，而MiR-126在CRC和Adenomas患者中抑制，它们与TNM分期相关，它们具有高诊断价值。 MiRNA调节的HIF-1 VEGF信号传导途径在结肠癌启动中起作用。据我们所知，这是我们社区CRC中这个MiRNA小组的第一次研究。这些数据表明，这些生物标志物可以是早期诊断，筛查和预测CRC预后的潜在新颖的非侵入性标志物。了解MiRNA对癌症产生癌症并理解调制VEGF的信号输出的作用的分子函数可能富有成效，降低了这种黑恶性肿瘤的进展。

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