MicroRNA in Gastric Cancer Development: Mechanisms and Biomarkers.

Fatimat Kipkeeva,Kristina Grishina,Maxim Nikulin,Alexandra Korotaeva,Alexander Karpukhin,Tatyana Muzaffarova,Pavel Apanovich,Danzan Mansorunov

doi:10.3390/diagnostics10110891

Fatimat Kipkeeva, Kristina Grishina + Show 6 more

Open Access

https://doi.org/10.3390/diagnostics10110891

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Journal: Diagnostics	Publication Date: Oct 31, 2020
Citations: 22	License type: CC BY 4.0

Affiliation: Research Centre for Medical Genetics

Abstract

Gastric cancer (GC) is one of the most common and difficult diseases to treat. The study of signaling pathway regulation by microRNA provides information on the mechanisms of GC development and is the basis for biomarker creation. In this study, a circuit of microRNA interactions with signaling pathways was constructed. The microRNAs, associated with metastasis and chemoresistance, are described. In most cases, microRNAs in GC regulate the Wnt/β-catenin, PI3K/AKT/mTOR, RAS/RAF/ERK/MAPK, NF-kB, TGF-β, and JAK/STAT pathways. Part of the microRNA acts on several target genes that function in different pathways. This often leads to an intensification of the induced processes. MicroRNAs have also been described that have the opposite effect on different pathways, causing different functional consequences. By acting on several target genes, or genes associated with several pathways, microRNAs can function in a signaling network. MicroRNAs associated with metastasis most often interact with the Wnt/β-catenin pathway. MicroRNAs affecting chemoresistance, in most cases, affect the regulators of apoptosis and are associated with the PI3K/AKT/mTOR pathway. The characteristics of microRNAs proposed as candidates for GC biomarkers were analyzed. The currently developed diagnostic and prognostic panels of microRNAs are also considered.

Highlights

Gastric cancer (GC) is the fourth most morbid and second most fatal cancer in the world and is a serious clinical problem due to late detection, resistance to chemotherapy, and poor prognosis [1]
This review considers the functioning of microRNA in the format of a signaling network: the effect of microRNA on several target genes, as well as on genes associated with several pathways
This review presents microRNAs involved in the pathogenesis of GC, and their relationship with signaling pathways was traced

Summary

Introduction

GC is the fourth most morbid and second most fatal cancer in the world and is a serious clinical problem due to late detection, resistance to chemotherapy, and poor prognosis [1]. New targets for the development of effective approaches to the treatment of GC, as well as informative diagnostic and prognostic biomarkers, are being actively pursued In this regard, microRNAs are of great interest. The interaction of microRNAs with signaling pathways has a number of features, which consist of different forms of regulation and are associated with the possibility of simultaneous action on several pathways These features can lead to various functional and clinical consequences that do not follow directly from the action of microRNA on a specific gene. The possibility of microRNA action on several genes, as well as the possibility of genes functioning in several pathways and crosstalk between paths, have not been considered These features are directly related to the choice of microRNAs for analysis as biomarkers or therapeutic targets.

Features of the microRNA Interaction with Signaling Pathways in GC

MicroRNAs and signaling pathways regulated by

MicroRNAs Associated with the Development of GC Chemoresistance and Signaling

MicroRNA as GC Prognostic and Diagnostic Markers

Findings

Conclusions