Genes of the microRNA biogenesis pathway are deregulated in
colorectal cancer

VYCHYTILOVÁ, Petra, Alena KOVAŘÍKOVÁ, Marek SVOBODA, Rostislav VYZULA and Ondřej SLABÝ. Genes of the microRNA biogenesis pathway are deregulated in colorectal cancer. In The Non-Coding Genome, Heidelberg, Germany. 2013.

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TY  - CONF
ID  - 1128506
AU  - Vychytilová, Petra - Kovaříková, Alena - Svoboda, Marek - Vyzula, Rostislav - Slabý, Ondřej
PY  - 2013
TI  - Genes of the microRNA biogenesis pathway are deregulated in colorectal cancer
KW  - colorectal cancer
KW  - miRNA biogenesis
KW  - biomarkers
KW  - therapeutic targets
N2  - MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides long that regulate gene expression on post-transcriptional level. Therefore, their production and maturation have to be strictly regulated. Their biogenesis starts with the transcription, which is followed by several steps that lead to processing of primary transcripts to mature miRNAs. Each step of this pathway is sophistically regulated and any disruption of control mechanisms may leads to the cancer occurrence. The aim of this study was to analyse the expression of the crucial genes involved in the biogenesis of miRNAs in colorectal cancer (CRC). Expression of 19 selected genes (EIF2C1-4, GEMIN4, DDX20, TARBP2, DICER1, XPO5, DROSHA, DGCR8, POLR2A, DDX5, DDX17, ADAR, ADARB1, TNRC6A, LIN28A/B) has been analysed in tumour tissues of 120 clinically characterized patients with CRC and in 120 parallel healthy tissues by qRT-PCR. Using Wilcoxon test, genes with different expression between tumour tissue and healthy tissue have been identified. Subsequently, Kruskal-Wallis test has been used to find any correlation with the clinical-pathological features of the patients. We have found significantly higher expression of POLRIIA, ADAR, ADARB1, DGCR8, DDX5, DDX17, DROSHA, XPO5, EIF2C1-C4, TARBP2, TNRC6A, GEMIN3, DDX20 and DICER1 (P < 0.0001) and significantly lower expression of LIN28A in tumour tissue of CRC patients. Moreover, negative correlation between the expression of AGO3 and clinical stage of patients (P = 0.0017) and grade (P = 0.0151) and positive correlation between the expression of DICER1 (P = 0.0230) and DROSHA (P = 0.0212) and grade of patients has been observed. Our results show that changes in the expression of genes associated with biogenesis of miRNAs may be associated not only with the origin, but also to progression of CRC and therefore, these molecules could serve as potential new biomarkers or therapeutic targets.
ER  -

Basic information
Original name	Genes of the microRNA biogenesis pathway are deregulated in colorectal cancer
Authors	VYCHYTILOVÁ, Petra (203 Czech Republic, belonging to the institution), Alena KOVAŘÍKOVÁ (203 Czech Republic, belonging to the institution), Marek SVOBODA (203 Czech Republic), Rostislav VYZULA (203 Czech Republic) and Ondřej SLABÝ (203 Czech Republic, guarantor, belonging to the institution).
Edition	The Non-Coding Genome, Heidelberg, Germany, 2013.

Other information
Original language	English
Type of outcome	Conference abstract
Field of Study	30200 3.2 Clinical medicine
Country of publisher	Germany
Confidentiality degree	is not subject to a state or trade secret
RIV identification code	RIV/00216224:14740/13:00065633
Organization unit	Central European Institute of Technology
Keywords in English	colorectal cancer; miRNA biogenesis; biomarkers; therapeutic targets
Tags	International impact, Reviewed
Changed by	Changed by: Mgr. Petra Vychytilová, Ph.D., učo 211789. Changed: 22/1/2014 12:09.

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs 18-25 nucleotides long that regulate gene expression on post-transcriptional level. Therefore, their production and maturation have to be strictly regulated. Their biogenesis starts with the transcription, which is followed by several steps that lead to processing of primary transcripts to mature miRNAs. Each step of this pathway is sophistically regulated and any disruption of control mechanisms may leads to the cancer occurrence. The aim of this study was to analyse the expression of the crucial genes involved in the biogenesis of miRNAs in colorectal cancer (CRC). Expression of 19 selected genes (EIF2C1-4, GEMIN4, DDX20, TARBP2, DICER1, XPO5, DROSHA, DGCR8, POLR2A, DDX5, DDX17, ADAR, ADARB1, TNRC6A, LIN28A/B) has been analysed in tumour tissues of 120 clinically characterized patients with CRC and in 120 parallel healthy tissues by qRT-PCR. Using Wilcoxon test, genes with different expression between tumour tissue and healthy tissue have been identified. Subsequently, Kruskal-Wallis test has been used to find any correlation with the clinical-pathological features of the patients. We have found significantly higher expression of POLRIIA, ADAR, ADARB1, DGCR8, DDX5, DDX17, DROSHA, XPO5, EIF2C1-C4, TARBP2, TNRC6A, GEMIN3, DDX20 and DICER1 (P < 0.0001) and significantly lower expression of LIN28A in tumour tissue of CRC patients. Moreover, negative correlation between the expression of AGO3 and clinical stage of patients (P = 0.0017) and grade (P = 0.0151) and positive correlation between the expression of DICER1 (P = 0.0230) and DROSHA (P = 0.0212) and grade of patients has been observed. Our results show that changes in the expression of genes associated with biogenesis of miRNAs may be associated not only with the origin, but also to progression of CRC and therefore, these molecules could serve as potential new biomarkers or therapeutic targets.

Links
NT13549, research and development project	Name: Vytvoření diagnostické sady cirkulujících mikroRNA pro neinvazivní časnou diagnostiku a sledování pacientů s kolorektálním karcinomem

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Genes of the microRNA biogenesis pathway are deregulated in colorectal cancer

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