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miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation

1
Department of Animal Physiology and Ethology, Faculty of Natural Sciences, Comenius University in Bratislava, 842 15 Bratislava, Slovakia
2
First Surgery Department, University Hospital, Comenius University in Bratislava, 811 07 Bratislava, Slovakia
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4633; https://doi.org/10.3390/ijms21134633
Received: 8 May 2020 / Revised: 24 June 2020 / Accepted: 27 June 2020 / Published: 29 June 2020
(This article belongs to the Section Molecular Genetics and Genomics)
Regulation of microRNA (miRNA) expression has been extensively studied with respect to colorectal cancer (CRC), since CRC is one of the leading causes of cancer mortality worldwide. Transcriptional control of miRNAs creating clusters can be, to some extent, estimated from cluster position on a chromosome. Levels of miRNAs are also controlled by miRNAs “sponging” by long non-coding RNAs (ncRNAs). Both types of miRNA regulation strongly influence their function. We focused on clusters of miRNAs found to be down-regulated in CRC, containing miR-1, let-7, miR-15, miR-16, miR-99, miR-100, miR-125, miR-133, miR-143, miR-145, miR-192, miR-194, miR-195, miR-206, miR-215, miR-302, miR-367 and miR-497 and analysed their genome position, regulation and functions. Only evidence provided with the use of CRC in vivo and/or in vitro models was taken into consideration. Comprehensive research revealed that down-regulated miRNA clusters in CRC are mostly located in a gene intron and, in a majority of cases, miRNA clusters possess cluster-specific transcriptional regulation. For all selected clusters, regulation mediated by long ncRNA was experimentally demonstrated in CRC, at least in one cluster member. Oncostatic functions were predominantly linked with the reviewed miRNAs, and their high expression was usually associated with better survival. These findings implicate the potential of down-regulated clusters in CRC to become promising multi-targets for therapeutic manipulation. View Full-Text
Keywords: proliferation; apoptosis; chemoresistance; survival; long ncRNA; methylation; angiogenesis; cell adhesion proliferation; apoptosis; chemoresistance; survival; long ncRNA; methylation; angiogenesis; cell adhesion
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Pidíkova, P.; Reis, R.; Herichova, I. miRNA Clusters with Down-Regulated Expression in Human Colorectal Cancer and Their Regulation. Int. J. Mol. Sci. 2020, 21, 4633.

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