Search

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The molecular mechanisms determining HCM phenotypes are incompletely understood. Myocardial biopsies were obtained from a group of patients with obstructive HCM (n = 23) selected for surgical myectomy and from 9 unused donor hearts (controls). A subset of tissue-abundant myectomy samples from HCM (n = 10) and controls (n = 6) was submitted to laser-capture microdissection to isolate cardiomyocytes. We investigated the relationship among clinical phenotype, cardiac myosin proteins (MyHC6, MyHC7, and MyHC7b) measured by optimized label-free mass spectrometry, the relative genes (MYH7, MYH7B and MYLC2), and the MyomiR network (myosin-encoded microRNA (miRs) and long-noncoding RNAs (Mhrt)) measured using RNA sequencing and RT-qPCR. MyHC6 was lower in HCM vs. controls, whilst MyHC7, MyHC7b, and MyLC2 were comparable. MYH7, MYH7B, and MYLC2 were higher in HCM whilst MYH6, miR-208a, miR-208b, miR-499 were comparable in HCM and controls. These results are compatible with defective transcription by active genes in HCM. Mhrt and two miR-499-target genes, SOX6 and PTBP3, were upregulated in HCM. The presence of HCM-associated mutations correlated with PTBP3 in myectomies and with SOX6 in cardiomyocytes. Additionally, iPSC-derived cardiomyocytes, transiently transfected with either miR-208a or miR-499, demonstrated a time-dependent relationship between MyomiRs and myosin genes. The transfection end-stage pattern was at least in part similar to findings in HCM myectomies. These data support uncoupling between myosin protein/genes and a modulatory role for the myosin/MyomiR network in the HCM myocardium, possibly contributing to phenotypic diversity and providing putative therapeutic targets. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiomyopathy. The molecular mechanisms determining HCM phenotypes are incompletely understood. Myocardial biopsies were obtained from a group of patients with obstructive HCM (n = 23) selected for surgical myectomy and from 9 unused donor hearts (controls). A subset of tissue-abundant myectomy samples from HCM (n = 10) and controls (n = 6) was submitted to laser-capture microdissection to isolate cardiomyocytes. We investigated the relationship among clinical phenotype, cardiac myosin proteins (MyHC6, MyHC7, and MyHC7b) measured by optimized label-free mass spectrometry, the relative genes (MYH7, MYH7B and MYLC2), and the MyomiR network (myosin-encoded microRNA (miRs) and long-noncoding RNAs (Mhrt)) measured using RNA sequencing and RT-qPCR. MyHC6 was lower in HCM vs. controls, whilst MyHC7, MyHC7b, and MyLC2 were comparable. MYH7, MYH7B, and MYLC2 were higher in HCM whilst MYH6, miR-208a, miR-208b, miR-499 were comparable in HCM and controls. These results are compatible with defective transcription by active genes in HCM. Mhrt and two miR-499-target genes, SOX6 and PTBP3, were upregulated in HCM. The presence of HCM-associated mutations correlated with PTBP3 in myectomies and with SOX6 in cardiomyocytes. Additionally, iPSC-derived cardiomyocytes, transiently transfected with either miR-208a or miR-499, demonstrated a time-dependent relationship between MyomiRs and myosin genes. The transfection end-stage pattern was at least in part similar to findings in HCM myectomies. These data support uncoupling between myosin protein/genes and a modulatory role for the myosin/MyomiR network in the HCM myocardium, possibly contributing to phenotypic diversity and providing putative therapeutic targets.

In many plant species, flower stigma secretions are important in early stages of sexual reproduction. Previous chemical analysis and proteomic characterization of these exudates provided insights into their biological function. Nevertheless, the presence of nucleic acids in the stigma exudates has not been previously reported. Here, we studied the stigma exudates of Pyrus communis , Pyrus pyrifolia , and Pyrus syriaca and showed them to harbor extracellular RNAs of various sizes. RNA sequencing revealed, for the first time, the presence of known Rosaceae mature microRNAs (miRs), also abundant in the stigma source tissue. Predicted targets of the exudate miRs in the Arabidopsis thaliana genome include genes involved in various biological processes. Several of these genes are pollen transcribed, suggesting possible involvement of exudate miRs in transcriptional regulation of the pollen. Moreover, extracellular miRs can potentially act across kingdoms and target genes of stigma interacting organisms/microorganisms, thus opening novel applicative avenues in Horticulture., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

Neurocysticercosis (NCC), a major cause of neurological morbidity worldwide, is caused by the larvae of Taenia solium. Cestodes secrete molecules that block the Th1 response of their hosts and induce a Th2 response permissive to their establishment. Mature microRNAs (miRs) are small noncoding RNAs that regulate gene expression and participate in immunological processes. To determine the participation of Taenia miRs in the immune response against cysticercosis, we constructed small RNA (sRNA) libraries from larvae of Taenia solium and Taenia crassiceps. A total of 12074504 and 11779456 sequencing reads for T. solium and T. crassiceps, respectively, were mapped to the genomes of T. solium and other helminths. Both larvae shared similar miRNome, and miR-10-5p was the most abundant in both species, followed by let-7-5p in T. solium and miR-4989-3p in T. crassiceps, whereas among the genus-specific miRs, miR-001-3p was the most abundant in both, followed by miR-002-3p in T. solium and miR-003a-3p in T. crassiceps. The sequences of these miRs were identical in both. Structure and target prediction analyses revealed that these pre-miRs formed a hairpin and had more than one target involved in immunoregulation. Culture of macrophages, RT-PCR and ELISA assays showed that cells internalized miR-10-5p and let-7-5p into the cytoplasm and the miRs strongly decreased interleukin 16 (Il6) expression, tumor necrosis factor (TNF) and IL-12 secretion, and moderately decreased nitric oxide synthase inducible (Nos2) and Il1b expression (pro-inflammatory cytokines) in M(IFN-γ) macrophages and expression of Tgf1b, and the secretion of IL-10 (anti-inflammatory cytokines) in M(IL-4) macrophages. These findings could help us understand the role of miRs in the host-Taenia relationship., (© 2019 The Author(s).)

Oxidative stress is an important underlying cause of many disease processes and may arise due to either increasing free radical generation or decreasing antioxidant defense systems. MicroRNAs (miRs) are 22-nucleotide non-coding RNAs that may regulate many intracellular processes; and, more recently, they have been implicated in the pathways for free radical generation leading to oxidative stress. However, conversely, there is evidence that miRs may have an antioxidant effect, thus miR expression may be critical for the maintenance of the normal redox state and cell homeostasis. This review addresses these discrepant and opposing miR actions on how they may modify and regulate the oxidative balance., (© 2018 Wiley Periodicals, Inc.)