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Comprehensive RNA Sequencing in Adenoma-Cancer Transition Identified Predictive Biomarkers and Therapeutic Targets of Human CRC.
Molecular Therapy - Nucleic Acids ( IF 6.5 ) Pub Date : 2020-02-04 , DOI: 10.1016/j.omtn.2020.01.031
Mingzhe Zhu 1 , Yanqi Dang 2 , Zhenhua Yang 3 , Yang Liu 4 , Li Zhang 2 , Yangxian Xu 4 , Wenjun Zhou 2 , Guang Ji 2
Affiliation  

Specific molecular biomarkers for predicting the transition from colorectal adenoma to cancer have been identified, however, circular RNA (circRNA)-related signatures remain to be clarified. We carried out high-throughput RNA sequencing to determine the expression profiles of circRNAs, microRNAs (miRNAs), and mRNAs in human colorectal cancer (CRC), adenoma, and adjacent normal tissues. We identified 84 circRNAs, 41 miRNAs, and 398 mRNAs that were commonly differentially expressed in CRC and adenoma tissues compared with normal tissues. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and protein-protein interaction (PPI) analyses identified numerous cancer-related hub genes that might serve as potential therapeutic targets in CRC. Competing endogenous RNA (ceRNA) networks, including three circRNAs, three miRNAs, and 28 mRNAs were constructed, suggesting their potential role in cancer progression. Representative differentially expressed RNAs were validated by the Cancer Genome Atlas (TCGA) database and real-time PCR experiments. Receiver operating characteristic (ROC) curve analysis identified three circRNAs (hsa_circ_0049487, hsa_circ_0066875, and hsa_circ_0007444) as possible novel biomarkers predicting the transition from colonic adenoma to cancer. Overall, our findings may provide novel perspectives to clarify the mechanisms of the transition from premalignant adenoma to cancer and identify specific circRNA-related signatures with possible applications for the early diagnosis of and as potential therapeutic targets in CRC.



中文翻译:

腺瘤-癌变过程中的综合RNA测序确定了人类CRC的预测生物标记物和治疗靶标。

已经确定了预测大肠腺瘤向癌症转变的特定分子生物标记,但是,与环状RNA(circRNA)相关的标记尚待阐明。我们进行了高通量的RNA测序,以确定circRNA,microRNA(miRNA)和mRNA在人大肠癌(CRC),腺瘤和邻近正常组织中的表达情况。我们鉴定出与正常组织相比,在CRC和腺瘤组织中通常差异表达的84个circRNA,41个miRNA和398个mRNA。基因本体论(GO),京都基因与基因组百科全书(KEGG)途径以及蛋白质-蛋白质相互作用(PPI)分析确定了许多与癌症相关的中枢基因,这些基因可能成为CRC的潜在治疗靶标。竞争性内源RNA(ceRNA)网络,包括三个circRNA,三个miRNA,并构建了28个mRNA,表明它们在癌症进展中的潜在作用。代表性差异表达的RNA已通过癌症基因组图谱(TCGA)数据库和实时PCR实验验证。接收者操作特征(ROC)曲线分析确定了三种circRNA(hsa_circ_0049487,hsa_circ_0066875和hsa_circ_0007444),它们可能是预测从结肠腺瘤向癌症过渡的新型生物标记。总体而言,我们的发现可能提供新颖的观点,以阐明从恶变前腺瘤向癌症转变的机制,并鉴定与circRNA相关的特定信号,并可能用于CRC的早期诊断和潜在治疗靶点。代表性差异表达的RNA已通过癌症基因组图谱(TCGA)数据库和实时PCR实验验证。接收者操作特征(ROC)曲线分析确定了三种circRNA(hsa_circ_0049487,hsa_circ_0066875和hsa_circ_0007444),它们可能是预测从结肠腺瘤向癌症过渡的新型生物标记。总体而言,我们的发现可能提供新颖的观点,以阐明从恶变前腺瘤向癌症转变的机制,并鉴定与circRNA相关的特定信号,并可能用于CRC的早期诊断和潜在治疗靶点。代表性差异表达的RNA已通过癌症基因组图谱(TCGA)数据库和实时PCR实验验证。接收者操作特征(ROC)曲线分析确定了三种circRNA(hsa_circ_0049487,hsa_circ_0066875和hsa_circ_0007444),它们可能是预测从结肠腺瘤向癌症过渡的新型生物标记。总体而言,我们的发现可能提供新颖的观点,以阐明从恶变前腺瘤向癌症转变的机制,并鉴定与circRNA相关的特定信号,并可能用于CRC的早期诊断和潜在治疗靶点。和hsa_circ_0007444)作为可能的新生物标记来预测从结肠腺瘤向癌症的转变。总体而言,我们的发现可能提供新颖的观点,以阐明从恶变前腺瘤向癌症转变的机制,并鉴定与circRNA相关的特定信号,并可能用于CRC的早期诊断和潜在治疗靶点。和hsa_circ_0007444)作为可能的新生物标记来预测从结肠腺瘤向癌症的转变。总体而言,我们的发现可能提供新颖的观点,以阐明从恶变前腺瘤向癌症转变的机制,并鉴定与circRNA相关的特定信号,并可能用于CRC的早期诊断和潜在治疗靶点。

更新日期:2020-02-04
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