Zhu Mingzhe, Dang Yanqi, Yang Zhenhua, Liu Yang, Zhang Li, Xu Yangxian, Zhou Wenjun, Ji Guang
Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China; School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Institute of Digestive Diseases, Longhua Hospital, China-Canada Center of Research for Digestive Diseases (ccCRDD), Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
Mol Ther Nucleic Acids. 2020 Jun 5;20:25-33. doi: 10.1016/j.omtn.2020.01.031. Epub 2020 Feb 4.
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.
用于预测结直肠腺瘤向癌症转变的特定分子生物标志物已被确定，然而，与环状RNA（circRNA）相关的特征仍有待阐明。我们进行了高通量RNA测序，以确定环状RNA、微小RNA（miRNA）和信使RNA（mRNA）在人类结直肠癌（CRC）、腺瘤及邻近正常组织中的表达谱。我们鉴定出84种环状RNA、41种miRNA和398种mRNA，它们在CRC和腺瘤组织中与正常组织相比普遍存在差异表达。基因本体论（GO）、京都基因与基因组百科全书（KEGG）通路及蛋白质-蛋白质相互作用（PPI）分析确定了许多与癌症相关的枢纽基因，这些基因可能成为CRC潜在的治疗靶点。构建了竞争性内源RNA（ceRNA）网络，包括三种环状RNA、三种miRNA和28种mRNA，表明它们在癌症进展中的潜在作用。通过癌症基因组图谱（TCGA）数据库和实时PCR实验对代表性差异表达RNA进行了验证。受试者工作特征（ROC）曲线分析确定了三种环状RNA（hsa_circ_0049487、hsa_circ_0066875和hsa_circ_0007444）作为预测结肠腺瘤向癌症转变的可能新型生物标志物。总体而言，我们的研究结果可能为阐明癌前腺瘤向癌症转变的机制提供新的视角，并识别出与环状RNA相关的特定特征，这些特征可能应用于CRC的早期诊断及作为潜在治疗靶点。
