Circular RNAs as microRNA sponges: evidence and controversies

2021 ◽  
Author(s):  
Morten T. Jarlstad Olesen ◽  
Lasse S. Kristensen
Keyword(s):  
Gene Regulation ◽  
Target Genes ◽  
Research Field ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Additional Layer ◽  
Complex Process ◽  
Non Coding Rnas ◽  
New Research ◽  
Microrna Sponges

Abstract Gene expression in eukaryotic cells is a complex process encompassing several layers of regulation at the transcriptional and post-transcriptional levels. At the post-transcriptional level, microRNAs (miRs) are key regulatory molecules that function by binding directly to mRNAs. This generally leads to less efficient translation of the target mRNAs. More recently, an additional layer of gene regulation has been discovered, as other molecules, including circular RNAs (circRNAs), may bind to miRs and thereby function as sponges or decoys resulting in increased expression of the corresponding miR target genes. The circRNAs constitute a large class of mainly non-coding RNAs, which have been extensively studied in recent years, in particular in the cancer research field where many circRNAs have been proposed to function as miR sponges. Here, we briefly describe miR-mediated gene regulation and the extra layer of regulation that is imposed by the circRNAs. We describe techniques and methodologies that are commonly used to investigate potential miR sponging properties of circRNAs and discuss major pitfalls and controversies within this relatively new research field.

scholarly journals Advances in the Identification of Circular RNAs and Research Into circRNAs in Human Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Shihu Jiao ◽  
Song Wu ◽  
Shan Huang ◽  
Mingyang Liu ◽  
Bo Gao
Keyword(s):  
Neurological Disorders ◽  
Closed Loop ◽  
Significant Proportion ◽  
Human Diseases ◽  
Circular Rnas ◽  
The Status ◽  
Research Questions ◽  
Non Coding Rnas ◽  
Microrna Sponges

Circular RNAs (circRNAs) are a class of endogenous non-coding RNAs (ncRNAs) with a closed-loop structure that are mainly produced by variable processing of precursor mRNAs (pre-mRNAs). They are widely present in all eukaryotes and are very stable. Currently, circRNA studies have become a hotspot in RNA research. It has been reported that circRNAs constitute a significant proportion of transcript expression, and some are significantly more abundantly expressed than other transcripts. CircRNAs have regulatory roles in gene expression and critical biological functions in the development of organisms, such as acting as microRNA sponges or as endogenous RNAs and biomarkers. As such, they may have useful functions in the diagnosis and treatment of diseases. CircRNAs have been found to play an important role in the development of several diseases, including atherosclerosis, neurological disorders, diabetes, and cancer. In this paper, we review the status of circRNA research, describe circRNA-related databases and the identification of circRNAs, discuss the role of circRNAs in human diseases such as colon cancer, atherosclerosis, and gastric cancer, and identify remaining research questions related to circRNAs.

Response to “No evidence of functional co-adaptation between clustered microRNAs”

2018 ◽  
Author(s):  
Yirong Wang ◽  
Hong Zhang ◽  
Jian Lu
Keyword(s):  
Target Genes ◽  
Long Term Evolution ◽  
Significant Feature ◽  
Transcriptional Level ◽  
Model Based ◽  
Term Evolution ◽  
Non Coding Rnas ◽  
Genomic Locations ◽  
Adaptation Model

AbstractmicroRNAs (miRNAs) are a class of endogenously expressed small non-coding RNAs that regulate target genes at the post-transcriptional level. One significant feature of miRNA is that their genomic locations are often clustered together in the genome. In a previous study (Wang, et al. 2016), we proposed a “functional co-adaptation” model to explain how clustering helps new miRNAs survive and develop functions during long-term evolution. In a manuscript recently posted at bioRxiv (doi:10.1101/274811), Marco claimed that he re-analyzed our data and came to a different conclusion. However, we found his analyses were conducted in an inappropriate approach. He also claimed that the absence of substitution in highly conserved miRNAs does not support the “functional co-adaption” model based on the misunderstanding of our model. In summary, the analyses and claims of Marco, which are flawed, do not refute our model.

Study on the Function of miRNA-155 Target Using Bioinformatics Methods

2013 ◽  
Vol 709 ◽  
pp. 858-861
Author(s):  
De Ming Han ◽  
Zi Jun Shen ◽  
Li Hui Zhao
Keyword(s):  
Protein Expression ◽  
Mirna Target ◽  
Target Gene ◽  
Target Genes ◽  
Gene Prediction ◽  
Diagnosis And Treatment ◽  
Transcriptional Level ◽  
Mirna Target Gene ◽  
Non Coding Rnas

MicroRNAs are small non-coding RNAs that act at the post-transcriptional level, regulating protein expression by repressing translation or destabilizing mRNA target. We searched information about miR-155 in miRBase. Target genes of miR-155 are predicted by four miRNA target gene prediction softwares. The result shows that miR-155 was involved in proliferation, differentiation and apoptosis. These results can contribute to further study on the role of microRNA in diagnosis and treatment of cancer.

scholarly journals Reproductive phasiRNAs regulate reprogramming of gene expression and meiotic progression in rice

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yu-Chan Zhang ◽  
Meng-Qi Lei ◽  
Yan-Fei Zhou ◽  
Yu-Wei Yang ◽  
Jian-Ping Lian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Regulation ◽  
Target Genes ◽  
Single Gene ◽  
Crop Improvement ◽  
Rapid Change ◽  
Crop Breeding ◽  
Future Studies ◽  
Meiotic Progression ◽  
Complex Process

AbstractPlant spermatogenesis is a complex process that directly affects crop breeding. A rapid change in gene abundance occurs at early meiosis prophase, when gene regulation is selective. However, how these genes are regulated remains unknown. Here, we show that rice reproductive phasiRNAs are essential for the elimination of a specific set of RNAs during meiotic prophase I. These phasiRNAs cleave target mRNAs in a regulatory manner such that one phasiRNA can target more than one gene, and/or a single gene can be targeted by more than one phasiRNA to efficiently silence target genes. Our investigation of phasiRNA-knockdown and PHAS-edited transgenic plants demonstrates that phasiRNAs and their nucleotide variations are required for meiosis progression and fertility. This study highlights the importance of reproductive phasiRNAs for the reprogramming of gene expression during meiotic progression and establishes a basis for future studies on the roles of phasiRNAs with a goal of crop improvement.

The mRNA and lncRNA landscape of the non-pregnant endometrium during the oestrus cycle in dairy goat

2019 ◽  
Vol 59 (10) ◽  
pp. 1803 ◽  
Author(s):  
Xiaorui Liu ◽  
Lei Zhang ◽  
Jiuzeng Cui ◽  
Sicheng Che ◽  
Yuexia Liu ◽  
...  
Keyword(s):  
Target Genes ◽  
Embryo Implantation ◽  
Differentially Expressed ◽  
Dairy Goat ◽  
Dairy Goats ◽  
Global Trends ◽  
Oestrus Cycle ◽  
Complex Process ◽  
Non Coding Rnas ◽  
Cyclic Changes

Cyclic changes in the endometrium are essential for embryo implantation in mammals; many studies report that such changes constitute a complex process involving numerous molecular mediators. In the present study, goat endometria at oestrus Day 5 and oestrus Day 15 were selected to systematically analyse the transcriptome using strand-specific Ribo-Zero RNA sequencing. Over 120 million high-quality paired-end reads were generated and 440400 transcripts were identified in the endometrial tissue of dairy goats. In total, 489 differentially expressed mRNAs and 854 differentially expressed long non-coding RNAs were identified when comparing the endometrium at goat endometria at oestrus Day 5 and oestrus Day 15. Neurotensin was found to play a potentially important role in the non-pregnant goat endometrium during the oestrus cycle. Furthermore, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses of the cis-target genes of the differentially expressed long non-coding RNAs showed that GO:0005198 (structural molecule activity) and ko04510 (focal adhesion) might be involved in cyclic endometrial changes. Taken together, the resulting transcriptomic profiles elucidate global trends in mRNA and lncRNA expression in non-pregnant endometria during the oestrus cycle in dairy goats.

scholarly journals Circular RNAs: Their Role in the Pathogenesis and Orchestration of Breast Cancer

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiao He ◽  
Tao Xu ◽  
Weijie Hu ◽  
Yufang Tan ◽  
Dawei Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Target Gene ◽  
Evolutionary Conservation ◽  
Therapeutic Strategies ◽  
Circular Rnas ◽  
Therapeutic Resistance ◽  
Transcriptional Level ◽  
Metastatic Progression ◽  
Single Chain ◽  
Non Coding Rnas

As one of the most frequently occurring malignancies in women, breast cancer (BC) is still an enormous threat to women all over the world. The high mortality rates in BC patients are associated with BC recurrence, metastatic progression to distant organs, and therapeutic resistance. Circular RNAs (circRNAs), belonging to the non-coding RNAs (ncRNAs), are connected end to end to form covalently closed single-chain circular molecules. CircRNAs are widely found in different species and a variety of human cells, with the features of diversity, evolutionary conservation, stability, and specificity. CircRNAs are emerging important participators in multiple diseases, including cardiovascular disease, inflammation, and cancer. Recent studies have shown that circRNAs are involved in BC progress by regulating gene expression at the transcriptional or post-transcriptional level via binding to miRNAs then inhibiting their function, suggesting that circRNAs may be potential targets for early diagnosis, treatment, and prognosis of BC. Herein, in this article, we have reviewed and summarized the current studies about the biogenesis, features, and functions of circRNAs. More importantly, we emphatically elucidate the pivotal functions and mechanisms of circRNAs in BC growth, metastasis, diagnosis, and drug resistance. Deciphering the complex networks, especially the circRNA-miRNA target gene axis, will endow huge potentials in developing therapeutic strategies for combating BC.

scholarly journals Direct Interaction of miRNA and circRNA with the Oncosuppressor p53: An Intriguing Perspective in Cancer Research

Cancers ◽  
2021 ◽  
Vol 13 (23) ◽  
pp. 6108
Author(s):  
Anna Rita Bizzarri ◽  
Salvatore Cannistraro
Keyword(s):  
Ubiquitin Ligase ◽  
Regulatory Networks ◽  
Direct Interaction ◽  
Circular Rnas ◽  
Transcriptional Level ◽  
Functional Inhibition ◽  
High Structural Stability ◽  
Non Coding Rnas ◽  
Novel Therapeutic Strategies ◽  
Transcription Factor P53

MicroRNAs (miRNAs) are linear single-stranded non-coding RNAs oligonucleotides, widely distributed in cells, playing a key role as regulators of gene expression at post-transcriptional level. Circular RNAs (circRNAs) are single-stranded RNA oligonucleotides forming a covalently closed continuous loop, which confers them a high structural stability and which may code for proteins or act as gene regulators. Abnormal levels or dysregulation of miRNA or circRNA are linked to several cancerous pathologies, so that they are receiving a large attention as diagnostic and prognostic tools. Some miRNAs and circRNAs are strongly involved in the regulatory networks of the transcription factor p53, which plays a pivotal role as tumor suppressor. Overexpression of miRNAs and/or circRNAs, as registered in a number of cancers, is associated to a concomitant inhibition of the p53 onco-suppressive function. Among other mechanisms, it was recently suggested that a functional inhibition of p53 could arise from a direct interaction between p53 and oncogenic miRNAs or circRNAs; a mechanism that might be reminiscent of the p53 inhibition by some E3 ubiquitin ligase such as MDM2 and COP1. Such evidence might deserve important implications for restoring the p53 anticancer functionality, and pave the way to intriguing perspectives for novel therapeutic strategies. In the present paper, the experimental evidence of the interaction between p53 and miRNAs and/or circRNAs is reviewed and discussed in connection with the development of new anticancer approaches.

scholarly journals Cancer-Associated circRNA–miRNA–mRNA Regulatory Networks: A Meta-Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Shaheerah Khan ◽  
Atimukta Jha ◽  
Amaresh C. Panda ◽  
Anshuman Dixit
Keyword(s):  
Regulatory Networks ◽  
Target Genes ◽  
Rna Binding ◽  
Meta Analysis ◽  
Study Data ◽  
Circular Rnas ◽  
Rna Molecules ◽  
Sequencing Technologies ◽  
Non Coding Rnas

Recent advances in sequencing technologies and the discovery of non-coding RNAs (ncRNAs) have provided new insights in the molecular pathogenesis of cancers. Several studies have implicated the role of ncRNAs, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and recently discovered circular RNAs (circRNAs) in tumorigenesis and metastasis. Unlike linear RNAs, circRNAs are highly stable and closed-loop RNA molecules. It has been established that circRNAs regulate gene expression by controlling the functions of miRNAs and RNA-binding protein (RBP) or by translating into proteins. The circRNA–miRNA–mRNA regulatory axis is associated with human diseases, such as cancers, Alzheimer’s disease, and diabetes. In this study, we explored the interaction among circRNAs, miRNAs, and their target genes in various cancers using state-of-the-art bioinformatics tools. We identified differentially expressed circRNAs, miRNAs, and mRNAs on multiple cancers from publicly available data. Furthermore, we identified many crucial drivers and tumor suppressor genes in the circRNA–miRNA–mRNA regulatory axis in various cancers. Together, this study data provide a deeper understanding of the circRNA–miRNA–mRNA regulatory mechanisms in cancers.

scholarly journals Emerging Role of MiR-192-5p in Human Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Fu-jia Ren ◽  
Yao Yao ◽  
Xiao-yu Cai ◽  
Guo-ying Fang
Keyword(s):  
Target Genes ◽  
Noncoding Rnas ◽  
Human Diseases ◽  
Circular Rnas ◽  
Biological Processes ◽  
Transcriptional Expression ◽  
Diagnosis And Prognosis ◽  
Infection Disease ◽  
Non Coding Rnas

MicroRNAs (miRNAs) are a type of small non-coding RNAs that play an essential role in numerous biological processes by regulating the post-transcriptional expression of target genes. Recent studies have demonstrated that miR-192-5p, a member of the miR-192 family, partakes in several human diseases, especially various cancers, including cancers of the lung, liver, and breast. Importantly, the levels of miR-192-5p are abundant in biofluids, including the serum and urine, and the exosomal levels of miR-192-5p in circulation can aid in the diagnosis and prognosis of various diseases, such as chronic hepatitis B (CHB) infection disease. Notably, recent studies suggest that miR-192-5p is regulated by long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs). However, there are no comprehensive overviews on the role of miR-192-5p in human diseases. This review discusses the significant studies on the role of miR-192-5p in various human diseases, with special emphasis on the diseases of the respiratory and digestive systems.

scholarly journals Circular RNAs: An emerging type of RNA in cancer

2017 ◽  
Vol 30 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Li-Dan Hou ◽  
Jing Zhang
Keyword(s):  
Rna Splicing ◽  
Protein Complexes ◽  
Predictive Biomarkers ◽  
Circular Rnas ◽  
Splice Donor ◽  
Associated Proteins ◽  
Non Coding Rnas ◽  
Rna Protein Complexes ◽  
Microrna Sponges ◽  
New Strategies

Circular RNAs (circRNAs), a novel type of widespread and diverse endogenous non-coding RNAs (ncRNAs), which are different from the linear RNAs, form a covalently closed continuous loop without 5’ or 3’ polarities. The majority of circRNAs are abundant, conserved and stable across different species, and exhibit tissue/developmental-stage-specific characteristics. They are generated primarily through a type of alternative RNA splicing called “back-splicing,” in which a downstream splice donor is joined to an upstream splice acceptor through splice skipping or direct splice. Recent studies have discovered circRNAs function as microRNA sponges, binding with RNA-associated proteins to form RNA–protein complexes and then regulating gene transcription and translation into polypeptides. Emerging evidence indicates that circRNAs play important roles in the regulation of the development and progression of multiple cancers by serving as potential diagnostic and predictive biomarkers involved in tumor growth and invasion and providing new strategies for cancer diagnosis and targeted therapy. In this review, we briefly delineate the diversity and characteristics of circRNAs and discuss the highlights of the biogenesis of circRNAs and their potential functions in tumor.

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