MicroRNAs Regulating Cytoskeleton Dynamics, Endocytosis, and Cell Motility—A Link Between Neurodegeneration and Cancer?

Gerasymchuk, Dmytro; Anastasiia, Hubiernatorova; Domanskyi, Andrii

doi:10.3389/fneur.2020.549006

Cited by 6 publications

(3 citation statements)

References 193 publications

(167 reference statements)

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“…Cells undergoing EMT lose their epithelial morphology to assume fibroblast-like structures and form protrusive and invasive structures that guide ECM remodeling, cell extravasation and organ colonization. The modulation of cell motility genes and miRNAs is a common trait of cancer dissemination [ 102 ]. Studies on HNSCC have revealed reduced levels of miR-198, able to target Daphnetin 1 (DAPH1), a protein that promotes directional migration by sequestering Arpin, a competitive inhibitor of the Actin-related proteins (Arp2/3) complex.…”

Section: Mirnas As Relevant Regulators Of Adhesion/migration/invasion...mentioning

confidence: 99%

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

Quirico

Orso

Cucinelli

et al. 2022

Cell. Mol. Life Sci.

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MicroRNAs (miRNAs) are small, non-coding RNAs about 22 nucleotides in length that regulate the expression of target genes post-transcriptionally, and are highly involved in cancer progression. They are able to impact a variety of cell processes such as proliferation, apoptosis and differentiation and can consequently control tumor initiation, tumor progression and metastasis formation. miRNAs can regulate, at the same time, metabolic gene expression which, in turn, influences relevant traits of malignancy such as cell adhesion, migration and invasion. Since the interaction between metabolism and adhesion or cell movement has not, to date, been well understood, in this review, we will specifically focus on miRNA alterations that can interfere with some metabolic processes leading to the modulation of cancer cell movement. In addition, we will analyze the signaling pathways connecting metabolism and adhesion/migration, alterations that often affect cancer cell dissemination and metastasis formation.

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Section: Mirnas As Relevant Regulators Of Adhesion/migration/invasion...mentioning

confidence: 99%

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

Quirico

Orso

Cucinelli

et al. 2022

Cell. Mol. Life Sci.

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“…miRNAs are generally transcribed by either RNA polymerase II or III, giving actin a role in their transcription due to its importance for the function of these polymerases [88, 90, 159, 160]. Several miRNAs have been shown to affect actin binding protein expression, which in turn can affect the cellular actin structures produced [161][162][163]. miRNAs, like mRNAs, can be exported to recipient cells where they can affect cell phenotype.…”

Section: Actin In Mrna Translation Suppression and Degradationmentioning

confidence: 99%

Actin dynamics in protein homeostasis

Williams

Rousseau

2022

Bioscience Reports

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Cell homeostasis is maintained in all organisms by the constant adjustment of cell constituents and organisation to account for environmental context. Fine-tuning of the optimal balance of proteins for the conditions, or protein homeostasis, is critical to maintaining cell homeostasis. Actin, a major constituent of the cytoskeleton, forms many different structures which are acutely sensitive to the cell environment. Furthermore, actin structures interact with and are critically important for the function and regulation of multiple factors involved with mRNA and protein production, protein regulation, and protein degradation. Altogether, actin is a key, if often overlooked, regulator of protein homeostasis across eukaryotes. In this review, we highlight these roles and how they are altered following cell stress, from mRNA transcription to protein degradation.

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“…miRNAs regulate gene expression usually by destabilizing target mRNAs or inhibiting their translation, which is commonly achieved by binding to 6–8 nt long seed region on 3′ untranslated regions (3′UTRs) of the target [ 6 ]. miRNAs have been shown to participate in multiple physiological processes, such as cell proliferation and differentiation, response to oxidative stress, endocytosis and cell motility [ 7 , 8 , 9 ]. Disruption in miRNA biogenesis is extensively studied in various pathological conditions, including neurodegenerative disorders [ 9 , 10 , 11 , 12 , 13 ], diabetes [ 14 ] and liver diseases [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Human-Specific Regulation of Neurotrophic Factors MANF and CDNF by microRNAs

Konovalova

Gerasymchuk

Arroyo

et al. 2021

IJMS

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Mesencephalic astrocyte derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) are novel evolutionary conserved trophic factors, which exhibit cytoprotective activity via negative regulation of unfolded protein response (UPR) and inflammation. Despite multiple reports demonstrating detrimental effect of MANF/CDNF downregulation, little is known about the control of their expression. miRNAs—small non-coding RNAs—are important regulators of gene expression. Their dysregulation was demonstrated in multiple pathological processes and their ability to modulate levels of other neurotrophic factors, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), was previously reported. Here, for the first time we demonstrated direct regulation of MANF and CDNF by miRNAs. Using bioinformatic tools, reporter assay and analysis of endogenous MANF and CDNF, we identified that miR-144 controls MANF expression, and miR-134 and miR-141 downregulate CDNF levels. We also demonstrated that this effect is human-specific and is executed via predicted binding sites of corresponding miRNAs. Finally, we found that miR-382 suppressed hCDNF expression indirectly. In conclusion, we demonstrate for the first time direct regulation of MANF and CDNF expression by specific miRNAs, despite the fact their binding sites are not strongly evolutionary conserved. Furthermore, we demonstrate a functional effect of miR-144 mediated regulation of MANF on ER stress response markers. These findings emphasize that (1) prediction of miRNA targets based on evolutionary conservation may miss biologically meaningful regulatory pairs; and (2) interpretation of miRNA regulatory effects in animal models should be cautiously validated.

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MicroRNAs Regulating Cytoskeleton Dynamics, Endocytosis, and Cell Motility—A Link Between Neurodegeneration and Cancer?

Cited by 6 publications

References 193 publications

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

miRNA-guided reprogramming of glucose and glutamine metabolism and its impact on cell adhesion/migration during solid tumor progression

Actin dynamics in protein homeostasis

Human-Specific Regulation of Neurotrophic Factors MANF and CDNF by microRNAs

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