The Experts below are selected from a list of 244170 Experts worldwide ranked by ideXlab platform
Man Ryul Lee - One of the best experts on this subject based on the ideXlab platform.
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mir 31 sdha axis regulates reprogramming efficiency through mitochondrial metabolism
Stem cell reports, 2016Co-Authors: Man Ryul Lee, Charlie Mantel, Sang A. Lee, Sung-hwan Moon, Hal E. BroxmeyerAbstract:Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (Mir-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. Mir-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless Mir-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the Mir-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.
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Mir-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism.
Stem cell reports, 2016Co-Authors: Man Ryul Lee, Charlie Mantel, Sang A. Lee, Sung-hwan Moon, Hal E. BroxmeyerAbstract:Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (Mir-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. Mir-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless Mir-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the Mir-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.
Hal E. Broxmeyer - One of the best experts on this subject based on the ideXlab platform.
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mir 31 sdha axis regulates reprogramming efficiency through mitochondrial metabolism
Stem cell reports, 2016Co-Authors: Man Ryul Lee, Charlie Mantel, Sang A. Lee, Sung-hwan Moon, Hal E. BroxmeyerAbstract:Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (Mir-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. Mir-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless Mir-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the Mir-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.
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Mir-31/SDHA Axis Regulates Reprogramming Efficiency through Mitochondrial Metabolism.
Stem cell reports, 2016Co-Authors: Man Ryul Lee, Charlie Mantel, Sang A. Lee, Sung-hwan Moon, Hal E. BroxmeyerAbstract:Metabolism is remodeled when somatic cells are reprogrammed into induced pluripotent stem cells (iPSCs), but the majority of iPSCs are not fully reprogrammed. In a shift essential for reprogramming, iPSCs use less mitochondrial respiration but increased anaerobic glycolysis for bioenergetics. We found that microRNA 31 (Mir-31) suppressed succinate dehydrogenase complex subunit A (SDHA) expression, vital for mitochondrial electron transport chain (ETC) complex II. Mir-31 overexpression in partially reprogrammed iPSCs lowered SDHA expression levels and oxygen consumption rates to that of fully reprogrammed iPSCs, but did not increase the proportion of fully reprogrammed TRA1-60(+) cells in colonies unless Mir-31 was co-transduced with Yamanaka factors, which resulted in a 2.7-fold increase in full reprogramming. Thus switching from mitochondrial respiration to glycolytic metabolism through regulation of the Mir-31/SDHA axis is critical for lowering the reprogramming threshold. This is supportive of multi-stage reprogramming whereby metabolic remodeling is fundamental.
Wolfgang Kummer - One of the best experts on this subject based on the ideXlab platform.
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Muscarinic acetylcholine receptor subtypes expressed by mouse bladder afferent neurons.
Neuroscience, 2010Co-Authors: R. Nandigama, Tamara Papadakis, Ulrich Schwantes, Thomas Bschleipfer, Michael Bonitz, Wolfgang KummerAbstract:Abstract Cell bodies of afferent neurons located in lumbosacral dorsal root ganglia (DRG) provide Aδ- and C-fibres to the urinary bladder, reporting bladder wall tension, volume and noxious stimuli. Recent studies suggested an involvement of muscarinic acetylcholine receptors (mAChRs) not only in detrusor contractility but also in modulating afferent function, and this has been linked to the beneficial effects of muscarinic antagonists in the treatment of overactive bladder. Here, we aimed to determine the inventory of mAChR subtypes expressed by bladder afferent neurons in the mouse. Bladder afferent neurons were identified by retrograde neuronal tracing using Fast Blue (FB) or 1, 1′-dioctadecyl-3, 3, 3′, 3′-tetramethylindocarbocyanine perchlorhydrate (DiI) injection into the detrusor muscle. DRG L6-S1 were recognized as the major location of bladder afferent perikarya with an additional smaller peak at L1/L2. Retrogradely labelled bladder afferents located in DRG L4-S2 were subjected to immunohistochemistry or to laser-assisted microdissection with subsequent RT-PCR to study expression of mAChRs subtypes M1R–M5R. Immunolabelling for mAChR subtype M2R, validated on DRG from M2R gene-deficient mice, demonstrated this subtype on 35% of FB-labelled bladder afferents. RT-PCR demonstrated expression of subtypes M2R, M3R and M4R, but not of M1R and M5R, in pooled samples (30 section profiles each) of laser microdissected DiI-labelled bladder afferent cell bodies. In conclusion, bladder afferent neurons express different subtypes of mAChRs (M2R, M3R and M4R). Thus, processing of sensory information from the bladder appears to be under direct cholinergic control.
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Muscarinic acetylcholine receptor subtypes expressed by mouse bladder afferent neurons.
Neuroscience, 2010Co-Authors: R. Nandigama, Tamara Papadakis, Ulrich Schwantes, Thomas Bschleipfer, Michael Bonitz, Wolfgang KummerAbstract:Cell bodies of afferent neurons located in lumbosacral dorsal root ganglia (DRG) provide Adelta- and C-fibres to the urinary bladder, reporting bladder wall tension, volume and noxious stimuli. Recent studies suggested an involvement of muscarinic acetylcholine receptors (mAChRs) not only in detrusor contractility but also in modulating afferent function, and this has been linked to the beneficial effects of muscarinic antagonists in the treatment of overactive bladder. Here, we aimed to determine the inventory of mAChR subtypes expressed by bladder afferent neurons in the mouse. Bladder afferent neurons were identified by retrograde neuronal tracing using Fast Blue (FB) or 1, 1'-dioctadecyl-3, 3, 3', 3'-tetramethylindocarbocyanine perchlorhydrate (DiI) injection into the detrusor muscle. DRG L6-S1 were recognized as the major location of bladder afferent perikarya with an additional smaller peak at L1/L2. Retrogradely labelled bladder afferents located in DRG L4-S2 were subjected to immunohistochemistry or to laser-assisted microdissection with subsequent RT-PCR to study expression of mAChRs subtypes M1R-M5R. Immunolabelling for mAChR subtype M2R, validated on DRG from M2R gene-deficient mice, demonstrated this subtype on 35% of FB-labelled bladder afferents. RT-PCR demonstrated expression of subtypes M2R, M3R and M4R, but not of M1R and M5R, in pooled samples (30 section profiles each) of laser microdissected DiI-labelled bladder afferent cell bodies. In conclusion, bladder afferent neurons express different subtypes of mAChRs (M2R, M3R and M4R). Thus, processing of sensory information from the bladder appears to be under direct cholinergic control.
Yinlong Zhao - One of the best experts on this subject based on the ideXlab platform.
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down regulation of microrna 31 5p inhibits proliferation and invasion of osteosarcoma cells through wnt β catenin signaling pathway by enhancing axin1
Experimental and Molecular Pathology, 2019Co-Authors: Xue Chen, Lili Zhong, Wenping Liu, Yinlong ZhaoAbstract:Abstract Objectives Recently, the role of microRNA-31-5p (Mir-31-5p) in gene expression regulation has been reported in various cancers. Studies have shown that Wnt/β-catenin signaling pathway is involved in the proliferation and invasion of osteosarcoma (OS) cells. Therefore, this study aims to probe into the regulatory role of Mir-31-5p targeting AXIN1 in OS cells through Wnt/β-catenin signaling pathway. Methods Firstly, microarray expression profiles were used to screen differentially expressed miRNAs associated with OS. Next, OS and normal fibrous connective tissues as well as OS cell lines were obtained for investigating the role of Mir-31-5p on OS. Then, the putative binding sites between Mir-31-5p and AXIN1 were predicted and verified. The regulatory effects of Mir-31-5p on proliferation and invasion as well as tumorigenic potential of OS cells targeting AXIN1 were also analyzed. Besides, the relationship between Mir-31-5p and Wnt/β-catenin signaling pathway was assessed by immunofluorescence staining. Results The microarray dataset GSE63939 showed that Mir-31-5p and AXIN1 were involved in OS. Mir-31-5p expression increased while the expression of AXIN1 decreased in OS tissues and cells. AXIN1 was identified as a target gene of Mir-31-5p, intense expression of which inhibited the transcription of AXIN1. Down-regulated Mir-31-5p suppressed proliferation, invasion and tumorigenicity of OS cells through promoting AXIN1. Decreased Mir-31-5p activated Wnt/β-catenin signaling pathway, as reflected by increased β-catenin translocation into nuclei, through up-regulating the transcription of AXIN1. Conclusions All in all, repression of Mir-31-5p targets AXIN1 to activate the Wnt/β-catenin signaling pathway, thus suppressing proliferation, invasion and tumorigenicity of OS cells.
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Down-regulation of microRNA-31-5p inhibits proliferation and invasion of osteosarcoma cells through Wnt/β-catenin signaling pathway by enhancing AXIN1.
Experimental and molecular pathology, 2019Co-Authors: Chen Xue, Lili Zhong, Liu Wenping, Yinlong ZhaoAbstract:Abstract Objectives Recently, the role of microRNA-31-5p (Mir-31-5p) in gene expression regulation has been reported in various cancers. Studies have shown that Wnt/β-catenin signaling pathway is involved in the proliferation and invasion of osteosarcoma (OS) cells. Therefore, this study aims to probe into the regulatory role of Mir-31-5p targeting AXIN1 in OS cells through Wnt/β-catenin signaling pathway. Methods Firstly, microarray expression profiles were used to screen differentially expressed miRNAs associated with OS. Next, OS and normal fibrous connective tissues as well as OS cell lines were obtained for investigating the role of Mir-31-5p on OS. Then, the putative binding sites between Mir-31-5p and AXIN1 were predicted and verified. The regulatory effects of Mir-31-5p on proliferation and invasion as well as tumorigenic potential of OS cells targeting AXIN1 were also analyzed. Besides, the relationship between Mir-31-5p and Wnt/β-catenin signaling pathway was assessed by immunofluorescence staining. Results The microarray dataset GSE63939 showed that Mir-31-5p and AXIN1 were involved in OS. Mir-31-5p expression increased while the expression of AXIN1 decreased in OS tissues and cells. AXIN1 was identified as a target gene of Mir-31-5p, intense expression of which inhibited the transcription of AXIN1. Down-regulated Mir-31-5p suppressed proliferation, invasion and tumorigenicity of OS cells through promoting AXIN1. Decreased Mir-31-5p activated Wnt/β-catenin signaling pathway, as reflected by increased β-catenin translocation into nuclei, through up-regulating the transcription of AXIN1. Conclusions All in all, repression of Mir-31-5p targets AXIN1 to activate the Wnt/β-catenin signaling pathway, thus suppressing proliferation, invasion and tumorigenicity of OS cells.
Shu Chun Lin - One of the best experts on this subject based on the ideXlab platform.
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MicroRNA Mir-31 targets SIRT3 to disrupt mitochondrial activity and increase oxidative stress in oral carcinoma
Cancer letters, 2019Co-Authors: Yu-yu Kao, Kuo-wei Chang, Chung-ji Liu, Chung-hsien Chou, Li-yin Yeh, Yi-fen Chen, Chun-yu Fan Chiang, Shu Chun LinAbstract:MicroRNA Mir-31 is implicated in the neoplastic process of various malignancies including oral squamous cell carcinoma (OSCC). Silent information regulator 3 (Sirtuin3 or SIRT3) is a NAD-dependent deacetylase that regulates metabolic process. Suppressor role of SIRT3 has been found in neoplasms. This study investigates the disruptions of Mir-31-SIRT3 cascade to explore their potential association with metabolic change in OSCC. We identified that Mir-31 directly targeted SIRT3 in OSCC cells, and a reverse correlation between Mir-31 expression and SIRT3 expression was noted in OSCC tumors. SIRT3 expression attenuated the Mir-31 enhanced tumor cell migration and invasion. It also reduced the tumorigenic potential of FaDu cell line. Mir-31-SIRT3 impaired the mitochondrial membrane potential and structural integrity. The dis-regulation of this axis also contributed to the genesis of oxidative stress. In addition, Mir-31 switched tumor cells from aerobic metabolism to glycolytic metabolism. This study provides novel evidences demonstrating the presence of Mir-31-mediated post-transcriptional regulation of SIRT3 in OSCC. The disruption of Mir-31-SIRT3 cascade and the consequential metabolic aberrances are involved in OSCC progression.
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Mir-31 is upregulated in oral premalignant epithelium and contributes to the immortalization of normal oral keratinocytes
Carcinogenesis, 2014Co-Authors: Pei-shih Hung, Shou-yen Kao, Kuo-wei Chang, Chung-ji Liu, Cheng-chieh Yang, Ting-yun Huang, Shu Chun LinAbstract:Abstract Oral squamous cell carcinoma (OSCC) is a prevalent malignancy worldwide. MicroRNAs are short non-coding RNAs that regulate gene expression and are crucial for tumorigenesis. Previously, we have identified that Mir-31 is frequently upregulated in OSCC and that this Mir-31 increase, together with downstream effector modulation, enhances oral carcinogenesis. We have identified higher levels of Mir-31 expression in oral potential malignant disorder (OPMD) tissues compared with normal oral mucosa. Exogenous Mir-31 and human telomerase reverse transcriptase (hTERT) expression were introduced into cultured normal oral keratinocytes (NOKs), which led to the immortalization; these lines were designated M31OK1 and M31OK3. These immortalized lines maintained the capability to undergo squamous differentiation. In addition, migration by both cell lines was attenuated by hTERT and Mir-31 knockdown. M31OK1 carries a p53 gene mutation at codon 273. A serum-tolerant subline, M31OK1-D, exhibits potent anchorage-independent growth that is attenuated by knockdown of both hTERT and Mir-31. Mir-31-targeted factors inhibiting HIF (FIH), which upregulated vascular endothelial growth factor (VEGF), was found crucial for oral tumorigenesis. The proliferation, migration and epithelial-mesenchymal transition of M31OK1-D are associated with downregulation of FIH and upregulation of VEGF, which require Mir-31 expression. High Mir-31 expression is correlated with higher VEGF expression and lower E-cadherin expression in OPMD tissue. It can be concluded that Mir-31 collaborates with hTERT to immortalize NOKs and that this may contribute to early stage oral carcinogenesis. The targeting of downstream factors by Mir-31 may further advance the neoplastic progression of immortalized NOKs, allowing them to become malignant.
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Passenger strand miRNA Mir-31* regulates the phenotypes of oral cancer cells by targeting RhoA.
Oral oncology, 2012Co-Authors: Kuo-wei Chang, Shou-yen Kao, Meng-miao Tsai, Chung-ji Liu, Mann-tin Lui, Shu Chun LinAbstract:Summary Objectives MicroRNAs (miRNAs) are endogenous small non-coding RNAs that negatively regular target gene expression by RNA interference. The processing of the pre-miRNA hairpin generates a miRNA duplex, which consists of a miRNA (guide strand) and a miRNA∗ (passenger strand). Mir-31 is an oncogenic miRNA and is up-regulated in oral squamous cell carcinoma (OSCC). Mir-31∗ shows a high level of conservation across species and, based on this, this study hypothesized that Mir-31∗ is a functional miRNA. Materials and Methods The expression of Mir-31 and Mir-31∗ in OSCC tissues and oral cells were analyzed. Functional studies were performed on OSCC cells. Results Mir-31∗ is up-regulated in OSCC tissues, but its expression is less abundant than Mir-31. Mir-31∗ decreases the proliferation and migration of both SAS and Fadu cells. Furthermore, Mir-31∗ targets the 3′UTR of RhoA and is able to down-regulate RhoA expression. Knockdown of RhoA expression is known to decrease the proliferation and migration of OSCC cells. However, up-regulation of both Mir-31 and Mir-31∗ by delivery of pre-Mir-31 does still enhance OSCC oncogenicity. Conclusion Mir-31∗ is a functional miRNA involving in regulating RhoA, and the activity of Mir-31∗’s activity seems to counteract the functions of Mir-31 during OSCC tumorigenesis.
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Exploiting salivary Mir-31 as a clinical biomarker of oral squamous cell carcinoma.
Head & neck, 2011Co-Authors: Chung-ji Liu, Shu Chun Lin, Cheng-chieh Yang, Hui-wen Cheng, Kuo-wei ChangAbstract:Background Oral carcinoma is an important malignancy throughout the world. MicroRNAs (miRNAs) are endogenously expressed, non-coding RNAs that regulate post-transcriptional levels of targeted mRNAs. MiRNA-31(Mir-31) is significantly upregulated in oral carcinoma tissues and plays oncogenic roles in oral carcinogenesis. Methods We analyzed the levels of Mir-31 in saliva of patients with oral carcinoma (n = 45), oral verrucous leukoplakia (n = 10), and control healthy individuals (n = 24) by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results Salivary Mir-31 was significantly increased in patients with oral carcinoma at all clinical stages, including very small tumors. However, our preliminary analysis showed no increase of salivary Mir-31in patients with oral verrucous leukoplakia relative to controls. The Mir-31 was more abundant in saliva than in plasma, suggesting salivary Mir-31 was a more sensitive marker for oral malignancy. After excision of oral carcinoma, salivary Mir-31 was remarkably reduced, indicating that most of the upregulated salivary Mir-31 came from tumor tissues. Conclusion Our results point to a potential application of salivary Mir-31 as a biomarker for early detection and postoperative follow-up of oral carcinoma. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
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Increase of microRNA Mir-31 level in plasma could be a potential marker of oral cancer.
Oral diseases, 2010Co-Authors: Chia-yuan Liu, Shou-yen Kao, Meng-miao Tsai, Kuo-wei Chang, Shu Chun LinAbstract:Oral Diseases (2010) 16, 360–364 Backgrounds: Oral squamous cell carcinoma (OSCC) is a worldwide disease. MicroRNAs are endogenously expressed non-coding RNAs that have important biological and pathological functions. Mir-31 was found markedly up-regulated in OSCC and several other malignancies. However, Mir-31 expression was also down-regulated in the metastasis process of breast carcinoma. Materials and methods: Using quantitative RT-PCR analysis, we identified plasma Mir-31 in OSCC patients (n = 43) and case controlled individuals (n = 21). Nine OSCC patients saliva were also analyzed. The Mann–Whitney test and Wilcoxon matched pairs test were used to compare the differences among the various clinical variants. Results: Mir-31 in plasma was significantly elevated in OSCC patients relative to age and sex-matched control individuals. This marker yielded a receiver operating characteristic curve area of 0.82 and an accuracy of 0.72 defined by leave-one-out cross-validation. In addition, the plasma Mir-31 in patients was remarkably reduced after tumor resection suggesting that this marker is tumor associated. Our preliminary analysis also demonstrated the feasibility of detecting the increase of Mir-31 in patient’s saliva. Conclusion: This study concluded that plasma Mir-31 could be validated a marker of OSCC for diagnostic uses.