Circular RNAs Acting as miRNAs’ Sponges and Their Roles in Stem Cells

Abstract

Circular RNAs (circRNAs), a novel type of endogenous RNAs, have become a subject of intensive research. It has been found that circRNAs are important players in cell differentiation and tissue homeostasis, as well as disease development. Moreover, the expression of circRNAs is usually not correlated with their parental gene expression, indicating that they are not only a steady-state by-product of mRNA splicing but a product of variable splicing under novel regulation. Sequence conservation analysis has also demonstrated that circRNAs have important non-coding functions. CircRNAs exist as a covalently closed loop form in mammalian cells, where they regulate cellular transcription and translation processes. CircRNAs are built from pre-messenger RNAs, and their biogenesis involves back-splicing, which is catalyzed by spliceosomes. The splicing reaction gives rise to three different types of intronic, exotic and exon–intron circular RNAs. Due to higher nuclease stability and longer half lives in cells, circRNAs are more stable than linear RNAs and have enormous clinical advantage for use as diagnostic and therapeutic biomarkers for disease. In recent years, it has been reported that circRNAs in stem cells play a crucial role in stem cell function. In this article, we reviewed the general feature of circRNAs and the distinct roles of circRNAs in stem cell biology, including regulation of stem cell self-renewal and differentiation. CircRNAs have shown unique expression profiles during differentiation of stem cells and could serve as promising biomarkers of these cells. As circRNAs play pivotal roles in stem cell regulation as well as the development and progression of various diseases, we also discuss opportunities and challenges of circRNA-based treatment strategies in future effective therapies for promising clinical applications.

Mesenchymal stem cells’ “garbage bags” at work: Treating radial nerve injury with mesenchymal stem cell-derived exosomes

“…Furthermore, MSC exosomes have demonstrated benefits in brain injury, accelerating recovery through neurosynaptic remodeling, neurogenesis, and angiogenesis[ 74 ]. Besides miRNAs, circRNAs are resistant to degradation, act as miRNA sponges in neural apoptosis, angiogenesis, and synaptic plasticity modulation, and hold immense promise for neuroregeneration[ 75 ]. MSC-derived exosomal lncRNAs have been reported to enhance neuronal survival and promote axonal regeneration after nerve injury.…”

circRNA-sponging: a pipeline for extensive analysis of circRNA expression and their role in miRNA sponging

“…An interesting question is hence, if TarPmiR is able to differentiate between circRNAs that are active miRNA sponges and those that have other functions. Previous research has defined three types of circular RNAs based on structural features -exonic circular (ecirc) RNAs, circular intronic RNA (ciRNA), and exon-intron circRNA (EIciRNA) [47][48][49]. It has been suggested that ecircRNAs function predominantly through a miRNA sponging effect in the cytoplasm whereas other circular RNA forms (e.g.…”

Circular RNA expression profiles and functional predication after restraint stress in the amygdala of rats

“…These attributes of circRNAs imply that they have unique biological functions rather than being a by-product of pre-mRNA processing. Over the last decade, many researchers have revealed that circRNAs can function as microRNA sponges, interact with RNA-binding proteins (RBPs), modulate alternative splicing and transcription, and even translate into polypeptides ( Patop et al, 2019 ; Huang et al, 2020 ; Xiao et al, 2022 ). Accumulating evidence indicates that circRNAs are involved in neurological disorders, including ischemic brain injury, Alzheimer’s disease, and PTSD ( Mo et al, 2020 ; Su et al, 2021 ; Du et al, 2022 ).…”