Understanding the Modus Operandi of MicroRNA Regulatory Clusters

Oliveira, Arthur C.; Bovolenta, Luiz Augusto; Alves, Larissa da Silva Ferreira; Figueiredo, LF Poli de; Ribeiro, Amanda O.; Campos, Vinícius Farias; Lemke, Ney; Pinhal, Danillo

doi:10.3390/cells8091103

Cited by 14 publications

(4 citation statements)

References 59 publications

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“…Different studies, however, show that miRNAs regulation involves a more complex post-transcriptional control, both repressing and activating gene expression. Groups of miRNAs can induce regulation of specific biological processes, coordinately acting on pathways of functionally related genes ( Oliveira et al, 2019 ). Employing our bioinformatics analyses and available clinical data, we hypothesize a mechanism used by SARS-CoV-2 to infect cells.…”

Section: Introductionmentioning

confidence: 99%

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

et al. 2020

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Over 313,000 SARS-CoV-2 positive cases have been confirmed in Italy as of 30 September 2020, and the number of deaths exceeding thirty-five thousand makes Italy among the list of most significantly affected countries in the world. Such an enormous occurrence of infections and death raises the urgent demand for effective available treatments. Discovering the cellular/molecular mechanisms of SARS-CoV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and how to plan any therapeutic approach. In this regard, we performed an in silico analysis to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. Consequently, we investigated the signalling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets, and functions. Our bioinformatics analysis predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with histone deacetylate (HDAC) pathway. Notably, our results identified ACE/ACE2-ATR1-Cholesterol-HDAC axis signals that also matched with some available clinical data. We hypothesize that the current and EMA-approved, SARS-CoV-2 off-label HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. Moreover, a ranked list of compounds is provided for further evaluation for safety, efficacy, and effectiveness.

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Section: Introductionmentioning

confidence: 99%

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

et al. 2020

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“…However, it has been reported that miRNAs regulation involves a more complex post-transcriptional control, both repressing and activating gene expression. Groups of miRNAs can induce regulation of speci c biological processes, coordinately acting on pathways of functionally related genes 12 . Employing our bioinformatics analyses and available clinical data, we hypothesize a mechanism used by SARS-CoV-2 to infect cells.…”

Section: Introductionmentioning

confidence: 99%

Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment

Teodori

Sestili

Madiai

et al. 2020

Preprint

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Over 180.000 SARS-COV-2 positive cases have been confirmed in Italy as April 20, with the number of deaths exceeding 23 thousand, making Italy the second Country for world COVID-19 deaths. Such enormous occurrence of infected and dead people raises the urgent demand of effective fast available treatments to control and diminish this pandemic. Discovering the cellular/molecular mechanisms of SARS-COV-2 pathogenicity is of paramount importance to understand how the infection becomes a disease and for therapeutically approaching it. From literature data, through a bioinformatics approach, an in silico analysis was performed, to predict the putative virus targets and evidence the already available therapeutics. Literature experimental results identified angiotensin-converting enzyme ACE and Spike proteins particularly involved in COVID-19. We thus investigate on the signaling pathways modulated by the two proteins through query miRNet, the platform linking miRNAs, targets and functions. We predicted microRNAs (miRs), miR-335-5p and miR-26b-5p, as being modulated by Spike and ACE together with deacetylate histones pathway HDAC. Our results matched with the available clinical data. We hypothesize the current and EMA-approved, SARS-COV-2 off-label, HDAC inhibitors (HDACis) drugs may be repurposed to limit or block host-virus interactions. A ranked list of compounds is given that can be tested.

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“…It is supposed that the target site spacing can influence cooperative repression. Although a great number of genes can be influenced by a single miR, in general, miRs act according to the cellular program in a specific cell type and target only a subset of transcripts [ 2 ]. However, the regulation of these processes is still poorly understood.…”

Section: Introductionmentioning

confidence: 99%

MiR-7 in Cancer Development

2021

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MicroRNAs (miRNAs) are short non-coding RNA involved in the regulation of specific mRNA translation. They participate in cellular signaling circuits and can act as oncogenes in tumor development, so-called oncomirs, as well as tumor suppressors. miR-7 is an ancient miRNA involved in the fine-tuning of several signaling pathways, acting mainly as tumor suppressor. Through downregulation of PI3K and MAPK pathways, its dominant role is the suppression of proliferation and survival, stimulation of apoptosis and inhibition of migration. Besides these functions, it has numerous additional roles in the differentiation process of different cell types, protection from stress and chromatin remodulation. One of the most investigated tissues is the brain, where its downregulation is linked with glioblastoma cell proliferation. Its deregulation is found also in other tumor types, such as in liver, lung and pancreas. In some types of lung and oral carcinoma, it can act as oncomir. miR-7 roles in cell fate determination and maintenance of cell homeostasis are still to be discovered, as well as the possibilities of its use as a specific biotherapeutic.

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Understanding the Modus Operandi of MicroRNA Regulatory Clusters

Cited by 14 publications

References 59 publications

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

MicroRNAs Bioinformatics Analyses Identifying HDAC Pathway as a Putative Target for Existing Anti‐COVID‐19 Therapeutics

Pathways and microRNAs bioinformatics analyses identifying possible existing therapeutics for COVID-19 treatment

MiR-7 in Cancer Development

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