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MicroRNA 生物发生途径基因在结直肠癌中失调。

MicroRNA Biogenesis Pathway Genes Are Deregulated in Colorectal Cancer.

机构信息

Central European Institute of Technology, Masaryk University, Kamenice 753/5, 62500 Brno, Czech Republic.

Department of Surgery, University Hospital Brno, Jihlavska 340/20, 62500 Brno, Czech Republic.

出版信息

Int J Mol Sci. 2019 Sep 10;20(18):4460. doi: 10.3390/ijms20184460.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs that post-transcriptionally regulate gene expression. Each step of their production and maturation has to be strictly regulated, as any disruption of control mechanisms may lead to cancer. Thus, we have measured the expression of 19 genes involved in miRNAs biogenesis pathway in tumor tissues of 239 colorectal cancer (CRC) patients, 17 CRC patients with liver metastases and 239 adjacent tissues using real-time PCR. Subsequently, the expression of analyzed genes was correlated with the clinical-pathological features as well as with the survival of patients. In total, significant over-expression of all analyzed genes was observed in tumor tissues as well as in liver metastases except for LIN28A/B. Furthermore, it was shown that the deregulated levels of some of the analyzed genes significantly correlate with tumor stage, grade, location, size and lymph node positivity. Finally, high levels of DROSHA and TARBP2 were associated with shorter disease-free survival, while the over-expression of XPO5, TNRC6A and DDX17 was detected in tissues of patients with shorter overall survival and poor prognosis. Our data indicate that changed levels of miRNA biogenesis genes may contribute to origin as well as progression of CRC; thus, these molecules could serve as potential therapeutic targets.

摘要

微小 RNA(miRNAs)是一种小型非编码 RNA,可对基因表达进行转录后调控。它们的生成和成熟过程中的每一步都必须受到严格调控,因为任何控制机制的破坏都可能导致癌症。因此,我们使用实时 PCR 测量了 239 例结直肠癌(CRC)患者、17 例肝转移 CRC 患者和 239 例相邻组织中 19 个参与 miRNA 生物发生途径的基因的表达。随后,分析基因的表达与临床病理特征以及患者的生存相关联。总的来说,在肿瘤组织和肝转移中观察到所有分析基因的显著过度表达,除了 LIN28A/B。此外,研究表明,一些分析基因的失调水平与肿瘤分期、分级、位置、大小和淋巴结阳性显著相关。最后,DROSHA 和 TARBP2 的高水平与无病生存时间缩短相关,而 XPO5、TNRC6A 和 DDX17 的过表达则在总生存时间较短和预后不良的患者组织中被检测到。我们的数据表明,miRNA 生物发生基因的水平变化可能有助于 CRC 的起源和进展;因此,这些分子可以作为潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2ff8/6770105/db6ecc95e26f/ijms-20-04460-g001.jpg

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