مقالات پذیرفته شده در سومین کنگره بین المللی زیست پزشکی
Circular RNA: Features,Functions and their correlation with diseases especially cancer
Circular RNA: Features,Functions and their correlation with diseases especially cancer
Sima Emadi Allahyari,1Mohammadreza Nooridaloii,2,*
1. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences 2. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences
Introduction: In early 2012, the world of science saw a fascinating discovery called circular RNA as a transcription product of thousands of genes in mice and humans. These circular RNAs have recently been grouped as the encoding RNA in an independent group that their remarkable difference with other RNAs is that these RNAs are not linear, in which two ends connect with a covalent connection creating a loop-shaped structure. These molecules play a role in regulating the expression of genes in mammals, and also, unlike other RNAs, they are very stable. These RNAs are created quite differently by means of a mechanism called back splicing. In this mechanism, in a molecule of RNA, exons or lariat- shaped introns are bonded at two ends of '3 and '5 with a covalent bond, creating circular structures that, unlike other common RNAs in the cytoplasm, are very stable. The circular RNAs act as mRNA sponge and form a set of RNA and protein that engage in transcription regulation by binding to RNA-related proteins. This suggests that these RNAs regulate gene expression at the transcriptional level and then they react by miRNAs. In fact, those circular RNAs that play a role in regulating the function of miRNAs also play a role in the onset and progression of the cancer. In tumor tissues, circular RNAs are reduced in comparison with normal tissues, and this may be for reasons like error occurs in the back splicing mechanism, degradation by unregulated miRNAs or increased cell proliferation. Recently circular RNAs have been identified in exosomic studies and in the movement of chromosomes in cancers, and there is found that the incorrect and abnormal attachment of these types of RNAs is related to drug resistance. Although it is thought that circular RNAs are non-coding, some of them are translated into functional proteins. So far, there are many unknowns about circular RNAs and the mechanism for regulating the expression of genes by them, but there is a lot of evidence to convince us that they will soon be used as biomarkers to diagnose diseases and therapeutic targets for cancers.
Methods: We reviewed 77 articles published between 1990 to 2017 that focusing on diseases such as heart diseases, diabetes and Alzheimer diseases also cancers such as colorectal cancer, stomach cancer and hepato cellular carcinoma.
Results: While the number of circRNAs with identified roles is increasing, there are still thousands of circRNAs for which the functions stay unidentified. It is possible that the majority of circRNAs have a single as yet unknown role or performance together to aid one unified role. Still, it is possible that a large portion of expressed circRNAs are non-functional and just ‘noisy’ by-products of splicing; circRNAs seem to be regulated and preserved, but may simply piggyback on the regulatory factors involved in linear mRNA splicing, which could have conserved binding patterns. Since the expression of a circRNA is connected to the expression of its host gene, it is challenging to investigation these functional questions using standard methods. A profounder understanding of circRNA biogenesis may permit us to specifically knock out circRNAs using genome-editing tools. This would open the door to testing for functional consequences of circRNA expression.
Nevertheless of their specific functional roles, circRNAs run fodder for many basic cell biological questions regarding their biogenesis, nuclear export and decay, and they may even prove useful as biomarkers of cellular states owing to their stability and dynamic expression.
Conclusion: Extensive research deepens our understanding of complex network of the circular RNA in the presence or absence of cancer and the early information shows their role in initiation, progression, and therapeutic resistance. The fact that there are specific circular RNAs in some specific diseases is proven and their regulatory functions will be considered as the prognostic and diagnostic biomarkers for application in the future therapeutic purposes. High sensitivity and specificity biomarkers have been used by many clinicians to diagnose disease, identify the high-risk populations, expand the targeted therapies, and evaluate response to the treatment. Most blood-based and body fluid biopsy analyzes are of interest due to the non-invasive or less invasive nature. Blood-based analysis allows the researcher to see response to treatment, resistance to treatment, or detect the real-time early recurrence. Although the number of circular RNAs with the known functions is increasing, there are thousands types of which with the unknown functions. The majority of circular RNAs may have a single known function or may play a single role together. It is possible that a large fraction of the circular RNAs, that are expressed but are not functional, are the byproducts of splicing. Knockout of the circular RNAs with the specific genomic editing tools may lead to understanding of their function. It is hoped that advances in the molecular and biochemical biotechnology, along with identifying studies in the functional, physiological, and histological details, will expand the circular RNA-based therapeutic approaches in the near future, and provide the basis for the successful and safe clinical functions.