MIMT1和LINC01550是在结直肠癌中下调的未知lncrna

IF 1.8 4区 医学 Q3 PATHOLOGY International Journal of Experimental Pathology Pub Date : 2023-02-02 DOI:10.1111/iep.12467
Faramarz Vejdandoust, Rahmaneh Moosavi, Nasrin Fattahi Dolatabadi, Atefeh Zamani, Hossein Tabatabaeian
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引用次数: 0

摘要

对结直肠癌分子基础的不完全了解,以及随后在早期诊断和有效治疗方面的限制,导致这种形式的恶性肿瘤成为全球癌症相关死亡的第二大常见原因。随着高通量分析技术的进步和诸如癌症基因组图谱计划(TCGA)等公共数据集的可用性,广泛的编码转录本已被分析,其潜在的作用模式已被绘制出来。然而,我们对非编码RNA失调的理解仍然存在巨大的差距。为此,我们使用生物信息学方法来筛选和评估结直肠癌中尚未被分析的长链非编码rna (lncRNAs)。我们分析了TCGA RNA-seq数据,并使用qPCR技术验证了表达模式。通过对内部临床样本的分析,real-time PCR方法发现,与配对的邻近正常组织相比,入选的lncRNAs MER1 Repeat Containing imprinting Transcript 1 (MIMT1)和Non-Protein Coding RNA 1550 (LINC01550)在结直肠癌肿瘤中表达下调。从机制上看,计算机实验结果表明,LINC01550可以形成一个复杂的竞争性内源性RNA (ceRNA)网络,导致结肠直肠癌相关基因的后续调控,如CUGBP ELAV -Like Family Member (CELF2)、polyy嘧啶束结合蛋白1 (PTBP1)和ELAV -Like RNA结合蛋白1 (ELAV1)。这项工作的发现表明,MIMT1和LINC01550可能是新的肿瘤抑制基因,可以进一步研究以评估它们在调节癌症信号通路中的作用。
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MIMT1 and LINC01550 are uncharted lncRNAs down-regulated in colorectal cancer

Incomplete knowledge of the molecular basis of colorectal cancer, with subsequent limitations in early diagnosis and effective treatment, has contributed to this form of malignancy becoming the second most common cause of cancer-related death worldwide. With the advances in high-throughput profiling techniques and the availability of public data sets such as The Cancer Genome Atlas Program (TCGA), a broad range of coding transcripts have been profiled and their underlying modes of action have been mapped. However, there is still a huge gap in our understanding of noncoding RNA dysregulation. To this end, we used a bioinformatics approach to shortlist and evaluate yet-to be-profiled long noncoding RNAs (lncRNAs) in colorectal cancer. We analysed the TCGA RNA-seq data and followed this by validating the expression patterns using a qPCR technique. Analysing in-house clinical samples, the real-time PCR method revealed that the shortlisted lncRNAs, that is MER1 Repeat Containing Imprinted Transcript 1 (MIMT1) and Non-Protein Coding RNA 1550 (LINC01550), were down-regulated in colorectal cancer tumours compared with the paired adjacent normal tissues. Mechanistically, the in silico results suggest that LINC01550 could form a complex competitive endogenous RNA (ceRNA) network leading to the subsequent regulation of colorectal cancer-related genes, such as CUGBP Elav-Like Family Member (CELF2), Polypyrimidine Tract Binding Protein 1 (PTBP1) and ELAV Like RNA Binding Protein 1 (ELAV1). The findings of this work indicate that MIMT1 and LINC01550 could be novel tumour suppressor genes that can be studied further to assess their roles in regulating the cancer signalling pathway(s).

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来源期刊
CiteScore
4.50
自引率
3.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: Experimental Pathology encompasses the use of multidisciplinary scientific techniques to investigate the pathogenesis and progression of pathologic processes. The International Journal of Experimental Pathology - IJEP - publishes papers which afford new and imaginative insights into the basic mechanisms underlying human disease, including in vitro work, animal models, and clinical research. Aiming to report on work that addresses the common theme of mechanism at a cellular and molecular level, IJEP publishes both original experimental investigations and review articles. Recent themes for review series have covered topics as diverse as "Viruses and Cancer", "Granulomatous Diseases", "Stem cells" and "Cardiovascular Pathology".
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