Discovery of Novel miRNAs in Colorectal Cancer: Potential Biological Roles and Clinical Utility

IF 3.6 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY Non-Coding RNA Pub Date : 2023-10-26 DOI:10.3390/ncrna9060065
Iael Weissberg Minutentag, Ana Laura Seneda, Mateus C. Barros-Filhos, Márcio de Carvalho, Vanessa G. P. Souza, Claudia N. Hasimoto, Marcelo P. T. Moraes, Fabio A. Marchi, Wan L. Lam, Patricia P. Reis, Sandra A. Drigo
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Abstract

Deregulated miRNAs are associated with colorectal cancer (CRC), with alterations depending on the tumor location. Novel tissue-specific miRNAs have been identified in different tumors and are associated with cancer. We used miRMaster to identify novel miRNAs in CRC from the TCGA and GEO data (discovery and validation groups). We used TCGA data from five tissues to analyze miRNA tissue specificity. miRDB was used to predict miRNA targets, and the UCSC Xena Browser was used to evaluate target expression. After successive analyses, we identified 15 novel miRNAs with the same expression patterns in CRC in both the discovery and validation groups. Four molecules (nov-miR-13844-5p, nov-miR-7154-5p, nov-miR-5035-3p, and nov-miR-590-5p) were differentially expressed in proximal and distal CRC. The nov-miR-3345-5p and nov-miR-13172-3p, which are upregulated in tumors, are only expressed in colorectal tissues. These molecules have been linked to a worse prognosis in right-sided colon and rectal carcinomas. An analysis revealed an association between eight novel miRNAs and 81 targets, mostly cancer-related genes, with varying expression based on tumor location. These findings provide new miRNAs with potential biological relevance, molecular biomarkers, and therapeutic targets for CRC treatment.
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结直肠癌中新型mirna的发现:潜在的生物学作用和临床应用
失调的mirna与结直肠癌(CRC)相关,其改变取决于肿瘤的位置。新的组织特异性mirna已经在不同的肿瘤中被发现,并与癌症相关。我们使用miRMaster从TCGA和GEO数据中识别CRC中的新mirna(发现组和验证组)。我们使用来自5个组织的TCGA数据来分析miRNA的组织特异性。使用miRDB预测miRNA靶点,使用UCSC Xena Browser评估靶点表达。经过连续分析,我们在发现组和验证组中确定了15个在CRC中具有相同表达模式的新型mirna。四种分子(nov-miR-13844-5p、nov-miR-7154-5p、nov-miR-5035-3p和nov-miR-590-5p)在CRC近端和远端差异表达。在肿瘤中上调的nov-miR-3345-5p和nov-miR-13172-3p仅在结直肠组织中表达。这些分子与右侧结肠癌和直肠癌的预后不良有关。一项分析显示,8种新型mirna与81个靶点(主要是癌症相关基因)之间存在关联,这些靶点的表达基于肿瘤位置的不同。这些发现为结直肠癌的治疗提供了具有潜在生物学相关性、分子生物标志物和治疗靶点的新mirna。
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来源期刊
Non-Coding RNA
Non-Coding RNA Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
6.70
自引率
4.70%
发文量
74
审稿时长
10 weeks
期刊介绍: Functional studies dealing with identification, structure-function relationships or biological activity of: small regulatory RNAs (miRNAs, siRNAs and piRNAs) associated with the RNA interference pathway small nuclear RNAs, small nucleolar and tRNAs derived small RNAs other types of small RNAs, such as those associated with splice junctions and transcription start sites long non-coding RNAs, including antisense RNAs, long ''intergenic'' RNAs, intronic RNAs and ''enhancer'' RNAs other classes of RNAs such as vault RNAs, scaRNAs, circular RNAs, 7SL RNAs, telomeric and centromeric RNAs regulatory functions of mRNAs and UTR-derived RNAs catalytic and allosteric (riboswitch) RNAs viral, transposon and repeat-derived RNAs bacterial regulatory RNAs, including CRISPR RNAS Analysis of RNA processing, RNA binding proteins, RNA signaling and RNA interaction pathways: DICER AGO, PIWI and PIWI-like proteins other classes of RNA binding and RNA transport proteins RNA interactions with chromatin-modifying complexes RNA interactions with DNA and other RNAs the role of RNA in the formation and function of specialized subnuclear organelles and other aspects of cell biology intercellular and intergenerational RNA signaling RNA processing structure-function relationships in RNA complexes RNA analyses, informatics, tools and technologies: transcriptomic analyses and technologies development of tools and technologies for RNA biology and therapeutics Translational studies involving long and short non-coding RNAs: identification of biomarkers development of new therapies involving microRNAs and other ncRNAs clinical studies involving microRNAs and other ncRNAs.
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