MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease

Nouws, Jessica; Wan, Feng; Finnemore, Eric; Roque, Willy; Kim, Sojin; Bazán, Isabel; Li, Chuanxing; Sköld, C. Magnus; Dai, Qile; Yan, Xiting; Chioccioli, Maurizio; Neumeister, Veronique; Britto, Clemente J.; Sweasy, Joann B.; Bindra, Ranjit S.; Wheelock, Åsa M.; Kaminski, Naftali; Lee, Patricia; Sauler, Maor

doi:10.1172/jci.insight.134218

Cited by 21 publications

(13 citation statements)

References 50 publications

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“…Second, while we focused on BCL-2 family proteins, miR-24-3p has also been shown to target mRNAs of other pro-apoptotic proteins such as FAF1 (FASassociated factor 1) and the senescence-associated protein p16 [31,32]. Furthermore, miR-24-3p has been shown to regulate the apoptosis-inducing DNA damage response and extrinsic apoptosis pathway [25], both of which could also mediate the impaired healing after loss or inhibition of miR-24-3p [33,34]. Finally, the presence/absence and function of miR-24 in immune cells also needs to be clarified in order to fully understand our results.…”

Section: Downregulation Of Bim Reduces the Induction Of Apoptosis Caused By Mir-24-3p Inhibitionmentioning

confidence: 99%

Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation

et al. 2021

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While apoptosis plays a significant role in intestinal homeostasis, it can also be pathogenic if overactive during recovery from inflammation. We recently reported that microRNA-24-3p (miR-24-3p) is elevated in the colonic epithelium of ulcerative colitis patients during active inflammation, and that it reduced apoptosis in vitro. However, its function during intestinal restitution following inflammation had not been examined. In this study, we tested the influence of miR-24-3p on mucosal repair by studying recovery from colitis in both novel miR-24-3p knockout and miR-24-3p-inhibited mice. We observed that knockout mice and mice treated with a miR-24-3p inhibitor had significantly worsened recovery based on weight loss, colon length, and double-blinded histological scoring. In vivo and in vitro analysis of miR-24-3p inhibition in colonic epithelial cells revealed that inhibition promotes apoptosis and increases levels of the pro-apoptotic protein BIM. Further experiments determined that silencing of BIM reversed the pro-apoptotic effects of miR-24-3p inhibition. Taken together, these data suggest that miR-24-3p restrains intestinal epithelial cell apoptosis by targeting BIM, and its loss of function is detrimental to epithelial restitution following intestinal inflammation.

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Section: Downregulation Of Bim Reduces the Induction Of Apoptosis Caused By Mir-24-3p Inhibitionmentioning

confidence: 99%

Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation

et al. 2021

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“…When DNA repair fails, the genomic integrity of the cell is disrupted and this can lead to cancer. Recent studies have suggested that microRNAs take a one of the important part in the regulation of the DNA repair network (Figure 1) [108][109][110].…”

Section: Micrornas and Dna Repair In Lung Cancermentioning

confidence: 99%

“…It was shown miR-24-3p plays a role as regulator of the cellular response to DNA damage in pathogenesis of Chronic Obstructive Pulmonary Disease (COPD) which is considered one of the risk factors for lung cancer. Nouws et al have shown that miR-24-3p suppressed homology-directed DNA repair by inhibition of BRCA1 expression in the cells of parenchymal lung tissue [109].…”

Section: Micrornas and Dna Repair In Lung Cancermentioning

confidence: 99%

Role of microRNAs in Lung Carcinogenesis Induced by Asbestos

Bersimbaev

Bulgakova

Aripova

et al. 2021

JPM

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MicroRNAs are a class of small noncoding endogenous RNAs 19–25 nucleotides long, which play an important role in the post-transcriptional regulation of gene expression by targeting mRNA targets with subsequent repression of translation. MicroRNAs are involved in the pathogenesis of numerous diseases, including cancer. Lung cancer is the leading cause of cancer death in the world. Lung cancer is usually associated with tobacco smoking. However, about 25% of lung cancer cases occur in people who have never smoked. According to the International Agency for Research on Cancer, asbestos has been classified as one of the cancerogenic factors for lung cancer. The mechanism of malignant transformation under the influence of asbestos is associated with the genotoxic effect of reactive oxygen species, which initiate the processes of DNA damage in the cell. However, epigenetic mechanisms such as changes in the microRNA expression profile may also be implicated in the pathogenesis of asbestos-induced lung cancer. Numerous studies have shown that microRNAs can serve as a biomarker of the effects of various adverse environmental factors on the human body. This review examines the role of microRNAs, the expression profile of which changes upon exposure to asbestos, in key processes of carcinogenesis, such as proliferation, cell survival, metastasis, neo-angiogenesis, and immune response avoidance.

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“…Cells were re-transfected after 72 hours and used for experimentation 24-48 hours after the second transfection, and after being incubated with 0% or 8% CSE for 20 hours. For CSE, mainstream smoke from one 3RF4 research cigarette (University of Kentucky, Lexington, Kentucky) was suctioned through 10 mL of cell culture media and filtered using a 0.22 μm filter (MilliporeSigma) as previously described, with the obtained filtrate considered 100% CSE 69 . Flow cytometry for Annexin V and propidium iodide was performed per the manufacturer's protocol (BD Biosciences, 556547) using a Cytoflex LX flow cytometer and data was analyzed using Flow Jo 10.6 software.…”

Section: Rna Sequencing Of Isolated At2 Cellsmentioning

confidence: 99%

Cell-Specific Transcriptome of the COPD Alveolar Niche

Sauler

McDonough

Adams

et al. 2021

Preprint

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Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide. To identify cell-specific mechanisms underlying COPD pathobiology, we analysed single-cell RNA sequencing (scRNAseq) profiles of explanted lung tissue from subjects with advanced COPD or control lungs. Findings were validated with scRNAseq of lungs from mice exposed to 10 months of cigarette smoke (CS), isolated human alveolar epithelial cells, and immunostaining of human lung tissue samples. We identified a subpopulation of alveolar epithelial type II cells with transcriptional evidence for aberrant cellular metabolism and reduced cellular stress tolerance, exemplified by decreased expression of the stress-response gene NUPR1. Network analyses identified an important role for inflamed capillary endothelial cells in COPD, particularly through CXCL-motif chemokine signalling. Finally, we detected a metallothionein expressing macrophage subpopulation unique to COPD. Collectively, these findings highlight cell-specific mechanisms involved in the pathobiology of advanced COPD.

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MicroRNA miR-24-3p reduces DNA damage responses, apoptosis, and susceptibility to chronic obstructive pulmonary disease

Cited by 21 publications

References 50 publications

Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation

Loss of miR-24-3p promotes epithelial cell apoptosis and impairs the recovery from intestinal inflammation

Role of microRNAs in Lung Carcinogenesis Induced by Asbestos

Cell-Specific Transcriptome of the COPD Alveolar Niche

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