Evidence map›Paper›PMID 34463266›Full record

ArticleBiomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2021

Gene-specific MicroRNA antagonism protects against HIV Tat and TGF-β-mediated suppression of CFTR mRNA and function.

R K Dutta, S Chinnapaiyan, M J Santiago, I Rahman, H J Unwalla

Open access · goldAbstract read
In one paragraph

Article in Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.9field-weighted citation impact, top 13% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 27 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

R K DuttaDepartment of Immunology and Nanomedicine, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
S ChinnapaiyanDepartment of Immunology and Nanomedicine, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
M J SantiagoDepartment of Immunology and Nanomedicine, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA.
I RahmanUniversity of Rochester Medical Center, Departments of Environmental Medicine and Pulmonary Medicine, Rochester, NY 14642, USA.
H J UnwallaDepartment of Immunology and Nanomedicine, Institute of Neuroimmune Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, FL, USA. Electronic address: hunwalla@fiu.edu.
Florida International University · USUniversity of Rochester Medical Center · US

Funding

Mechanisms of Defective Mitophagy and cellular Senescence in HIV-associated COPDR01HL147715 · NHLBI · FLORIDA INTERNATIONAL UNIVERSITY · PI IRFAN RAHMAN, HOSHANG JEHANGIR UNWALLA · 2019 to 2026
$2.6M
Transdisciplinary Training in Biomolecular and Biomedical SciencesT32GM132054 · NIGMS · FLORIDA INTERNATIONAL UNIVERSITY · PI DEGENNARO, MATTHEW, TSE-DINH, YUK-CHING · 2019 to 2023
$1.6M
Tracheobronchial mucociliary dysfunction in HIV patientsR21HL128141 · NHLBI · FLORIDA INTERNATIONAL UNIVERSITY · PI UNWALLA, HOSHANG JEHANGIR · 2016 to 2017
$410k
NHLBI NIH HHS R01 HL147715NHLBI NIH HHS R21 HL128141NIGMS NIH HHS T32 GM132054
6 · The paper itself

Abstract

backgroundMicroRNAs play an important role in health and disease. TGF-β signaling, upregulated by HIV Tat, and in chronic airway diseases and smokers upregulates miR-145-5p to suppress cystic fibrosis transmembrane conductance regulator (CFTR). CFTR suppression in chronic airway diseases like Cystic Fibrosis, COPD and smokers has been associated with suppressed MCC and recurrent lung infections and inflammation. This can explain the emergence of recurrent lung infections and inflammation in people living with HIV.

methodsTat-induced aberrant microRNAome was identified by miRNA expression analysis. microRNA mimics and antagomirs were used to validate the identified miRNAs involved in Tat mediated CFTR mRNA suppression. CRISPR-based editing of the miRNA target sites in CFTR 3'UTR was used to determine rescue of CFTR mRNA and function in airway epithelial cell lines and in primary human bronchial epithelial cells exposed to TGF-β and Tat.

findingsHIV Tat upregulates miR-145-5p and miR-509-3p. The two miRNAs demonstrate co-operative effects in suppressing CFTR. CRISPR-based editing of the miRNA target site preserves CFTR mRNA and function in airway epithelial cells

interpretationGiven the important roles of TGF-β signaling and the multitude of genes regulated by miRNAs, we demonstrate that CRISPR-based gene-specific microRNA antagonism approach can preserve CFTR mRNA and function in the context of HIV Tat and TGF-β signaling without suppressing expression of other genes regulated by miR-145-5p.

Indexed as

3' Untranslated RegionsBronchiCell LineCells, CulturedCRISPR-Cas SystemsCystic Fibrosis Transmembrane Conductance RegulatorEpithelial CellsGene EditingHumansMicroRNAsRNA, MessengerSignal Transductiontat Gene Products, Human Immunodeficiency VirusTransforming Growth Factor betaUp-Regulation3' Untranslated RegionsCFTR protein, humanCystic Fibrosis Transmembrane Conductance RegulatorMicroRNAsMIRN145 microRNA, humanMIRN509 microRNA, humanRNA, Messengertat Gene Products, Human Immunodeficiency VirusTransforming Growth Factor betaCRISPRGene therapyHIVMicroRNA

Identifiers

PMID34463266
PMCPMC9100877
OpenAlexW3197566026

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.