miR-711 upregulation induces neuronal cell death after traumatic brain injury

Sabirzhanov, Boris; Stoica, Bogdan A.; Zhao, Zhihong; Loane, David J.; Wu, Junfang; Dorsey, Susan G.; Faden, Alan I.

doi:10.1038/cdd.2015.132

Cited by 67 publications

(59 citation statements)

References 59 publications

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“…Consequently, the pro-apoptotic actions of p53 in neurons are considered to derive from transcriptional activation of PUMA (Engel et al, 2010), in accord with the over expression of PUMA alone in the absence of other insults being able to induce neuronal apoptosis (Cregan et al, 2004). In the present study, in accord with prior reports in TBI models (Plesnila et al, 2007; Sabirzhanov et al, 2016; Yang et al, 2015), PUMA was found up regulated in neurons and followed p53 expression. PFT-α (O) and PFT-α effectively suppressed this TBI-induced neuronal PUMA mRNA expression (Fig.…”

Section: Discussionsupporting

confidence: 93%

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

Yang

Greig

Huang

et al. 2016

Neurobiology of Disease

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Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Neuronal apoptosis in the hippocampus has been detected after TBI. The hippocampal dysfunction may result in cognitive deficits in learning, memory, and spatial information processing. Our previous studies demonstrated that a p53 inhibitor, pifithrin-α oxygen analogue (PFT-α (O)), significantly reduced cortical cell death, which is substantial following controlled cortical impact (CCI) TBI, and improved neurological functional outcomes via anti-apoptotic mechanisms. In the present study, we examined the effect of PFT-α (O) on CCI TBI-induced hippocampal cellular pathophysiology in light of this brain region’s role in memory. To investigate whether p53-dependent apoptosis plays a role in hippocampal neuronal loss and associated cognitive deficits and to define underlying mechanisms, SD rats were subjected to experimental CCI TBI followed by the administration of PFT-α or PFT-α (O) (2 mg/kg, i.v.) or vehicle at 5 h after TBI. Magnetic resonance imaging (MRI) scans were acquired at 24 h and 7 days post-injury to assess evolving structural hippocampal damage. Fluoro-Jade C was used to stain hippocampal sub-regions, including CA1 and dentate gyrus (DG), for cellular degeneration. Neurological functions, including motor and recognition memory, were assessed by behavioral tests at 7 days post injury. p53, p53 upregulated modulator of apoptosis (PUMA), 4-hydroxynonenal (4-HNE), cyclooxygenase-IV (COX IV), annexin V and NeuN were visualized by double immunofluorescence staining with cell-specific markers. Levels of mRNA encoding for caspase-3, p53, PUMA, Bcl-2, Bcl-2-associated X protein (BAX) and superoxide dismutase (SOD) were measured by RT-qPCR. Our results showed that post-injury administration of PFT-α and, particularly, PFT-α (O) at 5 h dramatically reduced injury volumes in the ipsilateral hippocampus, improved motor outcomes, and ameliorated cognitive deficits at 7 days after TBI, as evaluated by novel object recognition and open-field test. PFT-α and especially PFT-α (O) significantly reduced the number of FJC-positive cells in hippocampus CA1 and DG subregions, versus vehicle treatment, and significantly decreased caspase-3 and PUMA mRNA expression. PFT-α (O), but not PFT-α, treatment significantly lowered p53 and elevated SOD2 mRNA expression. Double immunofluorescence staining demonstrated that PFT-α (O) treatment decreased p53, annexin V and 4-HNE positive neurons in the hippocampal CA1 region. Furthermore, PUMA co-localization with the mitochondrial maker COX IV, and the upregulation of PUMA were inhibited by PFT-α (O) after TBI. Our data suggest that PFT-α and especially PFT-α (O) significantly reduce hippocampal neuronal degeneration, and ameliorate neurological and cognitive deficits in vivo via antiapoptotic and antioxidative properties.

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Section: Discussionsupporting

confidence: 93%

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

Yang

Greig

Huang

et al. 2016

Neurobiology of Disease

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“…To the best of our knowledge, there have been no studies that have investigated the role of miR-711 in human cancer. However, previous studies have investigated the role of miR-711 in organ injury and have reported miR-711 upregulation leading to various effects, including inhibition of collagen-1 expression in myocardial infarction and induction of neuronal cell death following traumatic brain injury (31). The present study reports that miR-711 is aberrantly overexpressed in breast cancer tissues; this is similar to results observed in cutaneous T-cell lymphoma, in which miR-711 is overexpressed (32).…”

Section: Discussionsupporting

confidence: 79%

MicroRNA-711 is a prognostic factor for poor overall survival and has an oncogenic role in breast cancer

Zhang

et al. 2016

Oncology Letters

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Abstract. MicroRNAs are important in cancer development and progression. In the present study, the clinical significance and function of microRNA-711 (miR-711) expression in breast cancer were investigated. The expression level of miR-711 was analyzed in breast cancer tissue samples using reverse transcription-quantitative polymerase chain reaction. Cell proliferation, colony formation, apoptosis and Transwell assays were performed in breast cancer cell lines transfected with miR-711 mimics or inhibitors, or control sequence. miR-711 was found to be upregulated in 30 formalin-fixed paraffin-embedded breast cancer tissue samples compared with paired non-cancerous breast tissues (P<0.05). Furthermore, a higher miR-711 expression was demonstrated to be associated with poor overall and disease-free survival times in 161 breast cancer patients, and miR-711 was identified as an independent prognostic factor using multivariate Cox regression analysis. In vitro, overexpression of miR-711 resulted in a significant increase in proliferation, colony formation, migration and invasion of breast cancer cells. By contrast, downregulating miR-711 inhibited cell proliferation, colony formation, migration and invasion and enhanced the rate of apoptosis of breast cancer cells. To the best of our knowledge, the present study is the first to demonstrate that miR-711 is an independent prognostic factor and serves an important oncogenic function in breast cancer, suggesting that miR-711 is a potential biomarker of prognosis and a molecular therapeutic target in breast cancer. IntroductionBreast cancer is the most common cancer and the leading cause of cancer-associated mortality in women worldwide (1). Breast cancer mortality rates have decreased in North America and several European countries over the past 25 years, principally due to earlier detection and improved treatments (2,3). However, in numerous African and Asian countries, the incidence and mortality rates have increased (4). Therefore, mortality from breast cancer remains a significant health issue globally. In general, the primary risk factors for breast cancer in women are old age (>50 years) and circulating estrogen (5). There are two strategies for enhancing the survival of breast cancer patients: Early detection and appropriate treatment. Primary treatments include surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapy. Studies have shown that the integrated use of a variety of treatments is advantageous to the prognosis of breast cancer patients (6). At present, formulation of a treatment plan, including surgery and adjuvant therapy, is primarily based on clinical stage and the presence of several limited biomarkers, including estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 (6). However, the tumor-node-metastasis staging system and these biomarkers do not meet the requirements for personalized therapy and/or precise therapy. Identifying biomarkers for precisely predicting prognosis or for future targeted thera...

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“…Possible targets of miR-2137 include solute carrier family 12 member 5, pleckstrin and Sec7 domain containing protein that are involved in chloride homeostasis in neurons and development and maintenance of dendritic spines (Meissner et al, 2015; Funk et al, 2008; Choi et al, 2006). Sabirzhanov et al (2016) showed that miR-711 upregulated after TBI in mouse cortex silences pro-survival Akt leading to neuronal death and administration of miR-711 hairpin inhibitor into injured cortex decreased the post-injury lesion volume, neuronal loss and behavioral deficits. TBI was also shown to downregulate miR-23a and miR-27a in mouse cortex following moderate CCI injury leading to an increase in their targets Noxa, Puma and Bax (Sabirzhanov et al, 2014).…”

Section: Non-coding Rnas and Tbimentioning

confidence: 99%

Non-coding RNAs and neuroprotection after acute CNS injuries

Chandran

Mehta

2017

Neurochemistry International

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Accumulating evidence indicates that various classes of non-coding RNAs (ncRNAs) including microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs) and long non-coding RNAs (lncRNAs) play important roles in normal state as well as the diseases of the CNS. Interestingly, ncRNAs have been shown to interact with messenger RNA, DNA and proteins, and these interactions could induce epigenetic modifications and control transcription and translation, thereby adding a new layer of genomic regulation. The ncRNA expression profiles are known to be altered after acute CNS injuries including stroke, traumatic brain injury and spinal cord injury that are major contributors of morbidity and mortality worldwide. Hence, a better understanding of the functional significance of ncRNAs following CNS injuries could help in developing potential therapeutic strategies to minimize the neuronal damage in those conditions. The potential of ncRNAs in blood and CSF as biomarkers for diagnosis and/or prognosis of acute CNS injuries has also gained importance in the recent years. This review highlighted the current progress in the understanding of the role of ncRNAs in initiation and progression of secondary neuronal damage and their application as biomarkers after acute CNS injuries.

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miR-711 upregulation induces neuronal cell death after traumatic brain injury

Cited by 67 publications

References 59 publications

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

Post-traumatic administration of the p53 inactivator pifithrin-α oxygen analogue reduces hippocampal neuronal loss and improves cognitive deficits after experimental traumatic brain injury

MicroRNA-711 is a prognostic factor for poor overall survival and has an oncogenic role in breast cancer

Non-coding RNAs and neuroprotection after acute CNS injuries

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