Changes in miRNA in the lung and whole blood after whole thorax irradiation in rats

Gao, Feng; Liu, Pengyuan; Narayanan, Jayashree; Yang, Ming; Fish, Brian L.; Liu, Yong; Liang, Mingyu; Jacobs, Elizabeth R.; Medhora, Meetha

doi:10.1038/srep44132

Cited by 32 publications

(26 citation statements)

References 56 publications

(84 reference statements)

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“…PDE5-I impacts the enzyme globally, including in the lung where PDE5 expression is prominent (33). To test if its effects on miR expression were organ independent, we examined lungs from normal and PO mice, assaying those known to be highly expressed in lung (34,35). All were confirmed as being reduced in PO+PDE5-I myocardium by qPCR and/or miR-seq, yet none were altered in lungs by PDE5-I under either condition ( Figure 5B and Supplemental Figure 4).…”

Section: Resultsmentioning

confidence: 99%

Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease

Kokkonen-Simon¹,

Saberi²,

Nakamura³

et al. 2018

JCI Insight

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MicroRNAs (miRs) posttranscriptionally regulate mRNA and its translation into protein, and are considered master controllers of genes modulating normal physiology and disease. There is growing interest in how miRs change with drug treatment, and leveraging this for precision guided therapy. Here we contrast 2 closely related therapies, inhibitors of phosphodiesterase type 5 or type 9 (PDE5-I, PDE9-I), given to mice subjected to sustained cardiac pressure overload (PO). Both inhibitors augment cyclic guanosine monophosphate (cGMP) to activate protein kinase G, with PDE5-I regulating nitric oxide (NO) and PDE9-I natriuretic peptide-dependent signaling. While both produced strong phenotypic improvement of PO pathobiology, they surprisingly showed binary differences in miR profiles; PDE5-I broadly reduces more than 120 miRs, including nearly half those increased by PO, whereas PDE9-I has minimal impact on any miR (P < 0.0001). The disparity evolves after pre-miR processing and is organ specific. Lastly, even enhancing NO-coupled cGMP by different methods leads to altered miR regulation. Thus, seemingly similar therapeutic interventions can be barcoded by profound differences in miR signatures, and reversing disease-associated miR changes is not required for therapy success.

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Section: Resultsmentioning

confidence: 99%

Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease

Kokkonen-Simon¹,

Saberi²,

Nakamura³

et al. 2018

JCI Insight

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“…Curating microRNAs as radiation markers has been gaining significant traction in recent years 13,[34][35][36] . The small endogenous RNA theoretically modulates up to 30% of the entire human genome and thereby regulates a wide variety of cellular and molecular functions.…”

Section: Discussionmentioning

confidence: 99%

microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation

Chakraborty

Gautam

Holmes-Hampton

et al. 2020

Sci Rep

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Lethal total body irradiation (TBI) triggers multifactorial health issues in a potentially short time frame. Hence, early signatures of TBI would be of great clinical value. Our study aimed to interrogate microRnA (miRNA) and metabolites, two biomolecules available in blood serum, in order to comprehend the immediate impacts of TBI. Mice were exposed to a lethal dose (9.75 Gy) of Cobalt-60 gamma radiation and euthanized at four time points, namely, days 1, 3, 7 and 9 post-TBI. Serum miRNA libraries were sequenced using the Illumina small RNA sequencing protocol, and metabolites were screened using a mass spectrometer. The degree of early impacts of irradiation was underscored by the large number of miRNAs and metabolites that became significantly expressed during the Early phase (day 0 and 1 post-TBI). Radiation-induced inflammatory markers for bone marrow aplasia and pro-sepsis markers showed early elevation with longitudinal increment. Functional analysis integrating miRNA-proteinmetabolites revealed inflammation as the overarching host response to lethal TBI. Early activation of the network linked to the synthesis of reactive oxygen species was associated with the escalated regulation of the fatty acid metabolism network. In conclusion, we assembled a list of time-informed critical markers and mechanisms of significant translational potential in the context of a radiation exposure event.

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“…A previous study has indicated that the expression of miR-144-5p, miR-144-3p, miR-142-5p, and miR-19a-3p in whole blood extends the lifespan of rats for 2 weeks after radiation [ 13 ]. However, little is known about the role of miR-144-5p in modifying the radiosensitivity of lung cancer cells.…”

Section: Introductionmentioning

confidence: 99%

miR-144-5p Enhances the Radiosensitivity of Non-Small-Cell Lung Cancer Cells via Targeting ATF2

Song

Peng

Hua

et al. 2018

BioMed Research International

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MicroRNAs (miRNAs or miRs) regulate gene expression at the posttranscriptional level and are involved in many biological processes such as cell proliferation and migration, stem cell differentiation, inflammation, and apoptosis. In particular, miR-144-3p is downregulated in various cancers, and its overexpression inhibits the proliferation and metastasis of cancer cells. However, the role of miR-144-5p in non-small-cell lung cancer (NSCLC), especially radiosensitivity, is unknown. In this study, we found that miR-144-5p was downregulated in NSCLC clinical specimens as well as NSCLC cell lines exposed to radiation. Enhanced expression of miR-144-5p promoted the radiosensitivity of NSCLC cells in vitro and A549 cell mouse xenografts in vivo. Furthermore, we identified activating transcription factor 2 (ATF2) as the direct and functional target of miR-144-5p using integrated bioinformatics analysis and a luciferase reporter assay. In addition, restoration of ATF2 expression inhibited miR-144-5p-induced NSCLC cell sensitivity to radiation in vitro and in vivo. Our findings suggest that deregulation of the miR-144-5p/ATF2 axis plays an important role in NSCLC cell radiosensitivity, thus representing a new potential therapeutic target for NSCLC.

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Changes in miRNA in the lung and whole blood after whole thorax irradiation in rats

Cited by 32 publications

References 56 publications

Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease

Marked disparity of microRNA modulation by cGMP-selective PDE5 versus PDE9 inhibitors in heart disease

microRNA and Metabolite Signatures Linked to Early Consequences of Lethal Radiation

miR-144-5p Enhances the Radiosensitivity of Non-Small-Cell Lung Cancer Cells via Targeting ATF2

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