RNA sequencing reveals an additional Crz1-binding motif in promoters of its target genes in the human fungal pathogen Candida albicans

Xu, Huihui; Fang, Tianshu; Omran, Raha Parvizi; Whiteway, Malcolm; Jiang, Lijing

doi:10.1186/s12964-019-0473-9

Cited by 135 publications

(127 citation statements)

References 61 publications

(100 reference statements)

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“…Regardless of the patterns of Dp or Dr changes, this elevated FA in the grey matter post-TBI has been associated with astrogliosis [ 25 , 27 ] or microstructural remodelling in a rat model of open-head injury [ 95 ]. Of particular interest is the association of DTI/NODDI changes and astrocyte activity, since astrocytes have dual roles in neuronal plasticity and reconstruction after traumatic brain injury [ 96 , 97 ].…”

Section: Discussionmentioning

confidence: 99%

A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging

Nasrallah

2021

acta neuropathol commun

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Concussion or mild traumatic brain injury is the most common form of traumatic brain injury with potentially long-term consequences. Current objective diagnosis and treatment options are limited to clinical assessment, cognitive rest, and symptom management, which raises the real danger of concussed patients being released back into activities where subsequent and cumulative injuries may cause disproportionate damages. This study conducted a cross-sectional multi-modal examination investigation of the temporal changes in behavioural and brain changes in a mouse model of concussion using magnetic resonance imaging. Sham and concussed mice were assessed at day 2, day 7, and day 14 post-sham or injury procedures following a single concussion event for motor deficits, psychological symptoms with open field assessment, T2-weighted structural imaging, diffusion tensor imaging (DTI), neurite orientation density dispersion imaging (NODDI), stimulus-evoked and resting-state functional magnetic resonance imaging (fMRI). Overall, a mismatch in the temporal onsets and durations of the behavioural symptoms and structural/functional changes in the brain was seen. Deficits in behaviour persisted until day 7 post-concussion but recovered at day 14 post-concussion. DTI and NODDI changes were most extensive at day 7 and persisted in some regions at day 14 post-concussion. A persistent increase in connectivity was seen at day 2 and day 14 on rsfMRI. Stimulus-invoked fMRI detected increased cortical activation at day 7 and 14 post-concussion. Our results demonstrate the capabilities of advanced MRI in detecting the effects of a single concussive impact in the brain, and highlight a mismatch in the onset and temporal evolution of behaviour, structure, and function after a concussion. These results have significant translational impact in developing methods for the detection of human concussion and the time course of brain recovery.

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Section: Discussionmentioning

confidence: 99%

A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging

Nasrallah

2021

acta neuropathol commun

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“…Further studies are required to warrant any conclusion. Moreover, recent report demonstrates that microRNA-941 protects endometrial cells from oxygen and glucose deprivation-re-oxygenation by activation of Nrf2 signalling through targeting Keap1, a Nrf2 suppressor protein 79 . Nrf2 overexpression promotes cancer progression and drug resistance in various cancers by activating several oncogenes such as matrix metallopeptidase 9, B-cell lymphoma 2, tumour necrosis factor α, and vascular endothelial growth factor A 80 – 82 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-941 regulates the proliferation of breast cancer cells by altering histone H3 Ser 10 phosphorylation

Surapaneni

Bhat

Tikoo

2020

Sci Rep

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Breast cancer including triple negative breast cancer (TNBC) represents an important clinical challenge, as these tumours often develop resistance to conventional chemotherapeutics. MicroRNAs play a crucial role in cell-cycle regulation, differentiation, apoptosis, and migration. Herein, we performed Affymetrix Gene Chip miRNA 4.0 microarray and observed differential regulation of miRNAs (75 upregulated and 199 downregulated) in metastatic MDA-MB-231 cells as compared to immortalized human non-tumorigenic breast epithelial (MCF-10A) cells. MicroRNA-941 was significantly upregulated in MDA-MB-231 cells (almost nine-fold increase) in comparison to MCF-10A cells. Transfection of MiRNA-941 inhibitor significantly decreased the proliferation and migration of MDA-MB-231 cells by altering the expressions of p21, Cyclin D1, PP2B-B1, E-cadherin and MMP-13. Interestingly, we provide first evidence that inhibiting miR-941 prevents cell proliferation and phosphorylation of histone H3 at Ser10 residue. Xenograft model of breast cancer was developed by subcutaneous injection of MDA-MB-231 cells into the mammary fat pad of female athymic nude mice (Crl:NU-Foxn1nu). The tumours were allowed to grow to around 60 mm3, thereafter which we divided the animals into seven groups (n = 5). Notably, intratumoral injection of miR-941 inhibitor significantly abolished the tumour growth in MDA-MB-231 xenograft model. 5-Fluorouracil (10 mg/kg, i.p.) was used as positive control in our study. To the best of our knowledge, we report for the first time that targeting miR-941 improves the sensitivity of MDA-MB-231 cells to 5-fluorouracil. This can be of profound clinical significance, as it provides novel therapeutic approach for treating variety of cancers (overexpressing miRNA-941) in general and breast cancers in particular.

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“…Defects in calcium homeostasis would lead to the retention of cytoplasmic calcium, which in turn activates calcineurin phosphatase activity [ 27 ]. The activated calcineurin will dephosphorylate zinc finger transcription factor Crz1, promoting nuclear translocation and induction of genes involved in azole resistance in Candida albicans [ 31 ]. Although the relationship between the calcineurin–Crz1 pathway and azole resistance has been determined, it is still unclear whether there is a direct relationship between the calcium signaling pathway and mitochondrial function.…”

Section: Role Of Fungal Mitochondria In Azole Resistancementioning

confidence: 99%

Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development

Song

Zhou

Zhang³

et al. 2020

Microorganisms

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In recent years, the role of mitochondria in pathogenic fungi in terms of azole resistance and fungal pathogenicity has been a rapidly developing field. In this review, we describe the molecular mechanisms by which mitochondria are involved in regulating azole resistance and fungal pathogenicity. Mitochondrial function is involved in the regulation of drug efflux pumps at the transcriptional and posttranslational levels. On the one hand, defects in mitochondrial function can serve as the signal leading to activation of calcium signaling and the pleiotropic drug resistance pathway and, therefore, can globally upregulate the expression of drug efflux pump genes, leading to azole drug resistance. On the other hand, mitochondria also contribute to azole resistance through modulation of drug efflux pump localization and activity. Mitochondria further contribute to azole resistance through participating in iron homeostasis and lipid biosynthesis. Additionally, mitochondrial dynamics play an important role in azole resistance. Meanwhile, mitochondrial morphology is important for fungal virulence, playing roles in growth in stressful conditions in a host. Furthermore, there is a close link between mitochondrial respiration and fungal virulence, and mitochondrial respiration plays an important role in morphogenetic transition, hypoxia adaptation, and cell wall biosynthesis. Finally, we discuss the possibility for targeting mitochondrial factors for the development of antifungal therapies.

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RNA sequencing reveals an additional Crz1-binding motif in promoters of its target genes in the human fungal pathogen Candida albicans

Cited by 135 publications

References 61 publications

A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging

A roadmap of brain recovery in a mouse model of concussion: insights from neuroimaging

MicroRNA-941 regulates the proliferation of breast cancer cells by altering histone H3 Ser 10 phosphorylation

Mitochondria-Mediated Azole Drug Resistance and Fungal Pathogenicity: Opportunities for Therapeutic Development

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