Abstract

Simple SummaryAs miRNAs show the capacity to be used as CRC biomarkers, we analysed experimentally validated data about frequently up-regulated miRNA clusters in CRC tissue. We identified 15 clusters that showed increased expression in CRC: miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224. Cluster positions in the genome are intronic or intergenic. Most clusters are regulated by several transcription factors, and by long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. The members of the selected clusters target 181 genes. Their functions and corresponding pathways were revealed with the use of Panther analysis. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.Colorectal cancer (CRC) is one of the most common malignancies in Europe and North America. Early diagnosis is a key feature of efficient CRC treatment. As miRNAs can be used as CRC biomarkers, the aim of the present study was to analyse experimentally validated data on frequently up-regulated miRNA clusters in CRC tissue and investigate their members with respect to clinicopathological characteristics of patients. Based on available data, 15 up-regulated clusters, miR-106a/363, miR-106b/93/25, miR-17/92a-1, miR-181a-1/181b-1, miR-181a-2/181b-2, miR-181c/181d, miR-183/96/182, miR-191/425, miR-200c/141, miR-203a/203b, miR-222/221, mir-23a/27a/24-2, mir-29b-1/29a, mir-301b/130b and mir-452/224, were selected. The positions of such clusters in the genome can be intronic or intergenic. Most clusters are regulated by several transcription factors, and miRNAs are also sponged by specific long non-coding RNAs. In some cases, co-expression of miRNA with other cluster members or host gene has been proven. miRNA expression patterns in cancer tissue, blood and faeces were compared. Based on experimental evidence, 181 target genes of selected clusters were identified. Panther analysis was used to reveal the functions of the target genes and their corresponding pathways. Clusters miR-17/92a-1, miR-106a/363, miR-106b/93/25 and miR-183/96/182 showed the strongest association with metastasis occurrence and poor patient survival, implicating them as the most promising targets of translational research.

Highlights

  • IntroductionThe present systematic review is focused on clusters of micro RNAs (miRNAs) with up-regulated expression in colorectal cancer (CRC) tissue showing potential for use as biomarkers

  • This article is an open access articleThe present systematic review is focused on clusters of micro RNAs with up-regulated expression in colorectal cancer (CRC) tissue showing potential for use as biomarkers

  • Our analysis revealed 34 long non-coding RNAs (lncRNA) validated as sponges for micro RNAs (miRNAs) from selected clusters in CRC cell lines (Table 2)

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Summary

Introduction

The present systematic review is focused on clusters of micro RNAs (miRNAs) with up-regulated expression in colorectal cancer (CRC) tissue showing potential for use as biomarkers. The highest CRC incidence rate has been revealed in Europe distributed under the terms and conditions of the Creative Commons. The incidence of CRC has increased mainly in the younger population (up to 55 years) in last two decades [1]. MiRNAs are a class of small non-coding RNAs with a length of approximately. Several miRNAs are already used in clinics as a diagnostic tool and/or in cancer treatment [4]. Biosynthesis of miRNAs consists of two processing steps. The primary miRNA transcript (pri-miRNA) is processed in the nucleus by the protein complex microprocessor containing the enzyme Drosha and the cofactor DGCR8 to generate a precursor miRNA (pre-miRNA). The second processing step, executed by the enzyme

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