Differential regulation of MCM7 and its intronic miRNA cluster miR-106b-25 during megakaryopoiesis induced polyploidy

Haldar, Srijan; Roy, Anita; Banerjee, Subrata

doi:10.4161/rna.36136

Cited by 12 publications

(16 citation statements)

References 32 publications

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“…This is also supported by our observations ( Fig. S8c ), as well as recent reports 38 – 40 , indicating an un-coupling of expression of the MCM7 gene (host gene for the miR-106b-25 cluster) with the differential expression of members of the miR-106b-25 cluster. Recently, miR25/93 has emerged as an important onco-miRNA during tumorigenesis 41 , and here we further reveal its function in inducing immunosuppressive phenotypes.…”

Section: Discussionsupporting

confidence: 93%

miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS

et al. 2017

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The mechanisms by which hypoxic tumors evade immunological pressure and anti-tumor immunity remain elusive. Here, we report that two hypoxia-responsive microRNAs, miR25 and miR93, are important for establishing an immunosuppressive tumor microenvironment by down-regulating expression of the DNA-sensor cGAS. Mechanistically, miR25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS upon hypoxia. This allows hypoxic tumor cells to escape immunological responses induced by damage-associated molecular pattern molecules (DAMPs), specifically the release of mtDNA. Moreover, restoring cGAS expression results in an anti-tumor immune response. Clinically, decreased levels of cGAS are associated with poor prognosis for patients with breast cancer harboring high levels of miR25/93. Together, these data suggest that inactivation of the cGAS pathway plays a critical role in tumor progression, and reveals a direct link between hypoxia-responsive miRNAs and adaptive immune responses to the hypoxic tumor microenvironment, thus unveiling potential new therapeutic strategies.

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Section: Discussionsupporting

confidence: 93%

miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS

et al. 2017

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“…MCM4 also had an identified seed match with hsa-miR-130b-3p. The miR-106b~25 cluster resides in the intron of MCM7 and these are co-transcribed [ 16 ]; however, we did not detect these expected expression associations. CDC6 is part of the pre-replicative complex and its presence facilitates MCM protein loading onto chromosomes [ 3 ].…”

Section: Discussioncontrasting

confidence: 69%

miRNA involvement in cell cycle regulation in colorectal cancer cases

et al. 2018

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Uncontrolled cell replication is a key component of carcinogenesis. MicroRNAs (miRNAs) regulate genes involved in checkpoints, DNA repair, and genes encoding for key proteins regulating the cell cycle. We investigated how miRNAs and mRNAs in colorectal cancer subjects interact to regulate the cell cycle.Using RNA-Seq data from 217 individuals, we analyzed differential expression (carcinoma minus normal mucosa) of 123 genes within the cell cycle pathway with differential miRNA expression, adjusting for age and sex. Multiple comparison adjustments for gene/miRNA associations were made at the gene level using an FDR <0.05. Differentially expressed miRNAs and mRNAs were tested for associations with colorectal cancer survival. MRNA and miRNA sequences were compared to identify seed region matches to support biological interpretation of the observed associations.Sixty-seven mRNAs were dysregulated with a fold change (FC) <0.67 or >1.50. Thirty-two mRNAs were associated with 48 miRNAs; 102 of 290 total associations had identified seed matches; of these, ten had negative beta coefficients. Hsa-miR-15a-5p and hsa-miR-20b-5p were associated with colorectal cancer survival with an FDR <0.05 (HR 0.86 95% CI 0.79, 0.94; HR 0.83 95% CI 0.75, 0.91 respectively).Our findings suggest that miRNAs impact mRNA translation at multiple levels within the cell cycle.

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“…Cdc6 binds to the replication origins first so that MCM proteins can bind [75]. Polyploid megakaryocytes show pronounced down regulation of MCM7 which goes through nonsense mediated decay (NMD) while its intronic miRNAs miR-106b-25 cluster is up-regulated [76]. Our results showed the up-regulated Cdc 6 with down-regulated MCM7 in the P. tricornutum cells in the grazing group indicate active replication of DNA response to the presence of grazing signals.…”

Section: Discussionmentioning

confidence: 63%

Transcriptome, Biochemical and Growth Responses of the Marine Phytoplankter Phaeodactylum Tricornutum Bohlin (Bacillariophyta) to Copepod Grazer Presence

Ismar

2018

Cell Physiol Biochem

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Background/Aims: As a model organism for a pleiomorphic marine planktonic primary producer, Phaeodactylum tricornutum has been studied on a molecular level under diverse cultural conditions. But little is known about its morphological, nutritional or transcriptomic responses under grazing stress. Methods: To assess microalgal molecular and cellular responses to grazer presence, we conducted transcriptome profiling in combination with growth rate, biovolume, fatty acid content, carbon and nitrogen content measurements in the model diatom Phaeodactylum tricornutum. RNA-sequencing was used to evaluate the transcriptomic response to grazing stress for P. tricornutum strain CCAP 1055/1. Results: Among the differentially expressed genes, we found down-regulation of genes involved in pathogen resistance, and in fatty acid biosynthesis pathways, while mitosis-involved genes were up-regulated. Experimentally testing morphological and biochemical responses in five strains of the species, we detected strain-specific significant effects of simulated grazing pressure in altered growth rates, biovolume and nutritional composition. Conclusion: Our research reveals the associated molecular and cellular responses to grazing effects in P. tricornutum and extends the understanding of co-evolutionary roles in regulating grazing defence between P. tricornutum and its grazer.

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Differential regulation of MCM7 and its intronic miRNA cluster miR-106b-25 during megakaryopoiesis induced polyploidy

Cited by 12 publications

References 32 publications

miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS

miR-25/93 mediates hypoxia-induced immunosuppression by repressing cGAS

miRNA involvement in cell cycle regulation in colorectal cancer cases

Transcriptome, Biochemical and Growth Responses of the Marine Phytoplankter Phaeodactylum Tricornutum Bohlin (Bacillariophyta) to Copepod Grazer Presence

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