Network Approaches to Study Endogenous RNA Competition and Its Impact on Tissue-Specific microRNA Functions

Marques, Tânia Monteiro; Gama‐Carvalho, Margarida

doi:10.3390/biom12020332

Cited by 10 publications

(8 citation statements)

References 74 publications

(88 reference statements)

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“…So called miRNA sponge activity is the most commonly described circRNA mechanism of action. This mechanism supports the endogenous RNA hypothesis, whereby specific RNA transcripts, such as circRNAs, can affect the abundance of other RNA molecules by limiting the availability of a common miRNA 54 . In other words, circRNAs inhibit miRNAs to positively regulate the expression of miRNA target genes 16 .…”

Section: Circular Rna Functionssupporting

confidence: 77%

Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

Mazziotta,

Badiale,

Cervellera

et al. 2024

Theranostics

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Human osteogenic differentiation is a complex and well-orchestrated process which involves a plethora of molecular players and cellular processes. A growing number of studies have underlined that circular RNAs (circRNAs) play an important regulatory role during human osteogenic differentiation. CircRNAs are single-stranded, covalently closed non-coding RNA molecules that are acquiring increased attention as epigenetic regulators of gene expression. Given their intrinsic high conformational stability, abundance, and specificity, circRNAs can undertake various biological activities in order to regulate multiple cellular processes, including osteogenic differentiation. The most recent evidence indicates that circRNAs control human osteogenesis by preventing the inhibitory activity of miRNAs on their downstream target genes, using a competitive endogenous RNA mechanism. The aim of this review is to draw attention to the currently known regulatory mechanisms of circRNAs during human osteogenic differentiation. Specifically, we provide an understanding of recent advances in research conducted on various human mesenchymal stem cell types that underlined the importance of circRNAs in regulating osteogenesis. A comprehensive understanding of the underlying regulatory mechanisms of circRNA in osteogenesis will improve knowledge on the molecular processes of bone growth, resulting in the potential development of novel preclinical and clinical studies and the discovery of novel diagnostic and therapeutic tools for bone disorders.

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Section: Circular Rna Functionssupporting

confidence: 77%

Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

Mazziotta,

Badiale,

Cervellera

et al. 2024

Theranostics

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“…miR‐129‐5p overexpression (oe) shelters from LPS‐induced podocyte apoptosis, inflammatory response, and acute kidney injury in in vivo and in vitro models of sepsis 13 . Moreover, lncRNAs that function as competitive endogenous RNAs (ceRNAs) can exert regulatory interactions on miRNAs 14 . It is identified and demonstrated that miR‐129‐5p can directly regulate MALAT1 and miR‐129‐5p mimics have the ability to restrain the development of colon cancer cells 15 .…”

Section: Introductionmentioning

confidence: 99%

“…13 Moreover, lncRNAs that function as competitive endogenous RNAs (ceRNAs) can exert regulatory interactions on miRNAs. 14 It is identified and demonstrated that miR-129-5p can directly regulate MA-LAT1 and miR-129-5p mimics have the ability to restrain the development of colon cancer cells. 15 LncRNA MALAT1 might play an important role in sustaining the potential osteoblast differentiation of bone mesenchymal stem cells through sponging miR-129-5p.…”

Section: Introductionmentioning

confidence: 99%

Long noncoding RNA MALAT1 inhibition attenuates sepsis‐induced acute lung injury through modulating the miR‐129‐5p/PAX6/ZEB2 axis

Liu

Xiao

Lin

2023

Microbiology and Immunology

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This research aimed to investigate the role of the long noncoding RNA metastasisassociated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-129-5p (miR-129-5p)/paired box gene 6 (PAX6) axis in sepsis-induced acute lung injury (ALI). MLE-12 cells and C57BL/6 mice were induced by LPS to establish lung injury in in vitro and in vivo models. Cell viability and apoptosis were measured by cell counting kit-8 assay and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining, respectively. Levels of inflammatory cytokines in cell supernatants and bronchoalveolar lavage fluid (BALF) were detected by ELISA. Lung injury was evaluated by lung wet weight-to-dry weight ratio and hematoxylin-eosin staining. MALAT1, PAX6, and zinc finger E-box-binding homeobox 2 (ZEB2) expression was elevated and miR-129-5p expression was reduced in the serum of patients with sepsis-induced ALI, LPS-induced MLE-12 cells, and lung tissues of ALI mice. MALAT1 interference delayed the LPS-induced cell proliferation decrease, apoptosis increase, and inflammatory factor increase. miR-129-5p inhibition could reverse the delaying effect of MALAT1 interference on LPS-induced lung cell injury. PAX6 overexpression (oe) reversed the inhibitory effect of miR-129-5p oe on LPSinduced lung cell injury. Downregulating MALAT1 reduced pulmonary edema, inflammatory cytokine levels, lung injury, and apoptosis in ALI mice. Moreover, miR-129-5p suppression or PAX6 oe reversed the delaying effect of MALAT1 interference on sepsis-induced ALI. MALAT1 aggravates sepsis-induced ALI via the miR-129-5p/PAX6/ZEB2 axis.

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“…However, simplistic approaches do not have the capacity to understand the intricated regulation mechanisms among these ncRNAs. Computational methods are crucial for integrating data as complex as the ncRNA interaction networks, whose crosstalk defines gene expression under determinate conditions (Marques and Gama-Carvalho, 2022). In this study, we obtained the ceRNA network and 22 lncRNA/miRNA/mRNA axes, which potentially control the response of astrocytes against high PA concentrations by mixing transcriptomic data and an in silico approach.…”

Section: Discussionmentioning

confidence: 99%

Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity

Gil-Jaramillo,

Aristizábal-Pachón,

Luque Aleman

et al. 2023

Front. Neurosci.

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Neurodegenerative diseases (NDs) are characterized by a progressive deterioration of neuronal function, leading to motor and cognitive damage in patients. Astrocytes are essential for maintaining brain homeostasis, and their functional impairment is increasingly recognized as central to the etiology of various NDs. Such impairment can be induced by toxic insults with palmitic acid (PA), a common fatty acid, that disrupts autophagy, increases reactive oxygen species, and triggers inflammation. Although the effects of PA on astrocytes have been addressed, most aspects of the dynamics of this fatty acid remain unknown. Additionally, there is still no model that satisfactorily explains how astroglia goes from being neuroprotective to neurotoxic. Current incomplete knowledge needs to be improved by the growing field of non-coding RNAs (ncRNAs), which is proven to be related to NDs, where the complexity of the interactions among these molecules and how they control other RNA expressions need to be addressed. In the present study, we present an extensive competing endogenous RNA (ceRNA) network using transcriptomic data from normal human astrocyte (NHA) cells exposed to PA lipotoxic conditions and experimentally validated data on ncRNA interaction. The obtained network contains 7 lncRNA transcripts, 38 miRNAs, and 239 mRNAs that showed enrichment in ND-related processes, such as fatty acid metabolism and biosynthesis, FoxO and TGF-β signaling pathways, prion diseases, apoptosis, and immune-related pathways. In addition, the transcriptomic profile was used to propose 22 potential key controllers lncRNA/miRNA/mRNA axes in ND mechanisms. The relevance of five of these axes was corroborated by the miRNA expression data obtained in other studies. MEG3 (ENST00000398461)/hsa-let-7d-5p/ATF6B axis showed importance in Parkinson’s and late Alzheimer’s diseases, while AC092687.3/hsa-let-7e-5p/[SREBF2, FNIP1, PMAIP1] and SDCBP2-AS1 (ENST00000446423)/hsa-miR-101-3p/MAPK6 axes are probably related to Alzheimer’s disease development and pathology. The presented network and axes will help to understand the PA-induced mechanisms in astrocytes, leading to protection or injury in the CNS under lipotoxic conditions as part of the intricated cellular regulation influencing the pathology of different NDs. Furthermore, the five corroborated axes could be considered study targets for new pharmacologic treatments or as possible diagnostic molecules, contributing to improving the quality of life of millions worldwide.

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Network Approaches to Study Endogenous RNA Competition and Its Impact on Tissue-Specific microRNA Functions

Cited by 10 publications

References 74 publications

Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

Long noncoding RNA MALAT1 inhibition attenuates sepsis‐induced acute lung injury through modulating the miR‐129‐5p/PAX6/ZEB2 axis

Competing endogenous RNAs in human astrocytes: crosstalk and interacting networks in response to lipotoxicity

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