Let-7a Inhibits T-Cell Proliferation and IFN-γ Secretion by Down-Regulating STAT3 Expression in Patients with Psoriasis

Hu, Xiaoping; Xie, Qian; Chen, Chaofeng; Zhang, Wei; Yu, Bo

doi:10.1159/000477120

Cited by 19 publications

(22 citation statements)

References 40 publications

(43 reference statements)

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“…As previously reported, miRNAs have the ability to post‐transcriptionally mediate the expression of numerous genes . Moreover, it has demonstrated that STAT3 is one of the target genes of let‐7a . A prior study concluded that let‐7a targets and negatively regulates STAT3 in HCC cells .…”

Section: Discussionmentioning

confidence: 80%

“…32 Moreover, it has demonstrated that STAT3 is one of the target genes of let-7a. 15 A prior study concluded that let-7a targets and negatively regulates STAT3 in HCC cells. 33 The targeting relationship between let-7c and STAT3 in alveolar macrophages has been speculated in previous reports.…”

Section: Discussionmentioning

confidence: 99%

“…Bioinformatics website (http://www.mirdb.org/) presented data indicating that there were putative binding sites between let‐7d, let‐7a‐1, and let‐7f‐1 and 3’‐untranslated region (3’UTR) of STAT3. Moreover, STAT3 has been reported to be a target of let‐7a in a previous study . Based on the aforementioned exploration of literature, we subsequently proposed a hypothesis that miR cluster MC‐let‐7a‐1 ~ let‐7d may be involved in glioma development by regulating STAT3.…”

Section: Introductionmentioning

confidence: 86%

“…Moreover, STAT3 has been reported to be a target of let-7a in a previous study. 15 Based on the aforementioned exploration of literature, we subsequently proposed a hypothesis that miR cluster MC-let-7a-1 ~ let-7d may be involved in glioma development by regulating STAT3. Hence, the study was designed to investigate the mechanism by which the miR cluster MC-let-7a-1 ~ let-7d influences the autophagy of glioma cells in connection to STAT3.…”

Section: Introductionmentioning

confidence: 99%

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microRNA cluster MC‐let‐7a‐1~let‐7d promotes autophagy and apoptosis of glioma cells by down‐regulating STAT3

et al. 2019

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Background Accumulating evidence has highlighted the correlation between microRNAs (miRNAs) and the progression of glioma. However, the role of miR cluster MC‐let‐7a‐1 ~ let‐7d in glioma remains elusive. Thus, the current study aimed to investigate the effect of miR cluster MC‐let‐7a‐1 ~ let‐7d on glioma progression. Methods and Results Microarray data analysis provided data indicating the involvement of miR cluster MC‐let‐7a‐1 ~ let‐7d in glioma via STAT3. The expression of let‐7a‐1, let‐7d, let‐7f‐1, and miR cluster MC‐let‐7a‐1 ~ let‐7d was diminished in the glioma tissues and the cell lines. Additionally, our results revealed that STAT3 was a target gene of let‐7d, let‐7a‐1, and let‐7f‐1, which was further verified by the dual‐luciferase reporter gene assay. Moreover, STAT3 expression was negatively mediated by let‐7a‐1, let‐7d, and let‐7f‐1. Up‐regulated miR cluster MC‐let‐7a‐1 ~ let‐7d or silenced STAT3 suppressed cell proliferation but accelerated cell apoptosis and autophagy. Moreover, restrained tumor growth was identified in the nude mice treated with miR cluster MC‐let‐7a‐1 ~ let‐7d mimics or STAT3 siRNA. Conclusion Taken together, the miR cluster MC‐let‐7a‐1 ~ let‐7d promotes glioma cell autophagy and apoptosis by repressing STAT3. The current study highlights the potential of the miR cluster MC‐let‐7a‐1 ~ let‐7d as biomarkers and promising treatment strategies for glioma.

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Section: Discussionmentioning

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 86%

Section: Introductionmentioning

confidence: 99%

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microRNA cluster MC‐let‐7a‐1~let‐7d promotes autophagy and apoptosis of glioma cells by down‐regulating STAT3

et al. 2019

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“…Hence, lack of good knowledge of etiopathogenesis impairs the development of an effective treatment. However, recent studies of molecular mechanisms in psoriatic patients give a new promise for effective therapy [25][26][27].…”

Section: Introductionmentioning

confidence: 99%

Psoriasis Treatment Changes the Expression Profile of Selected Caspases and their Regulatory MicroRNAs

Wcisło‐Dziadecka¹,

Simka²,

Kaźmierczak³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Psoriasis, an autoimmune diseases of the skin, characterized by patches of abnormal/inflammed skin, although not usually life-threatening, it causes severe discomfort, esthetic impairments, and may lead to impaired social functions and social withdrawal. Besides UV-phototherapy, various anti-inflammatory treatments are applied, depending on the severity of symptoms. In 2008, adalimumab (fully humanized human anti-TNF antibody) was launched for the treatment of psoriasis. In the quest to better understand the pathomechanism of adalimumab’s therapeutic effects, and the acquired resistance to the drug, we have investigated how its administration affect the regulation of the expression of selected caspases, including those activated by inflammosome. Methods: The research was initially carried out on normal human dermal fibroblasts (NHDF) treated with adalimumab for 2, 8 and 24 hours in vitro. Then, expression profile of genes encoding caspases and their regulatory micro-RNAs was determined with the use of oligonucleotide microarray. The validation of the microarray results was carried out by qRT-PCR. The in vitro study was followed by ex-vivo investigation of adalimumab’s effects on the expression of caspase-6 in blood of the psoriatic patients. The samples were collected before, and 2 hours after adalimumab’s administration and the analysis was determined by qRT-PCR. Results: The result of the analysis indicated that introduction of adalimumab to the NHDF culture resulted in the change of the transcription activity of genes encoding caspases and genes encoding miRNAs. The analysis revealed 5 different miRNA molecules regulating the expression of: CASP2, CASP3 and CASP6. There were no statistically significant differences in the expression of gene encoding caspase-6 in the patients’ blood before and 2 hours after the anti-TNF drug administration. Conclusion: We have found that adalimumab administration affects caspases expression, thus they may be used as molecular markers for monitoring the therapy with the use of an anti-TNF drugs, including adalimumab. It is likely that the mechanisms responsible for changed expression profiles of genes encoding caspase-2,-3, and -6, may be caused by the upregulation of the respective microRNA molecules. Increased expression of genes encoding specific caspases may induce inflammatory processes, as well as trigger apoptosis. Furthermore, the proapoptotic activity of caspases may be enhanced by miRNA molecules, which exhibit proapoptotic function. The overexpression of such miRNAs was observed in our study.

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Expression profiling of microRNAs in human bone tissue from postmenopausal women

et al. 2017

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Bone tissue is composed of several cell types, which express their own microRNAs (miRNAs) that will play a role in cell function. The set of total miRNAs expressed in all cell types configures the specific signature of the bone tissue in one physiological condition. The aim of this study was to explore the miRNA expression profile of bone tissue from postmenopausal women. Tissue was obtained from trabecular bone and was analyzed in fresh conditions (n = 6). Primary osteoblasts were also obtained from trabecular bone (n = 4) and human osteoclasts were obtained from monocyte precursors after in vitro differentiation (n = 5). MicroRNA expression profiling was obtained for each sample by microarray and a global miRNA analysis was performed combining the data acquired in all the microarray experiments. From the 641 miRNAs detected in bone tissue samples, 346 (54%) were present in osteoblasts and/or osteoclasts. The other 46% were not identified in any of the bone cells analyzed. Intersection of osteoblast and osteoclast arrays identified 101 miRNAs shared by both cell types, which accounts for 30-40% of miRNAs detected in these cells. In osteoblasts, 266 miRNAs were detected, of which 243 (91%) were also present in the total bone array, representing 38% of all bone miRNAs. In osteoclasts, 340 miRNAs were detected, of which 196 (58%) were also present in the bone tissue array, representing 31% of all miRNAs detected in total bone. These analyses provide an overview of miRNAs expressed in bone tissue, broadening our knowledge in the microRNA field.

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Let-7a Inhibits T-Cell Proliferation and IFN-γ Secretion by Down-Regulating STAT3 Expression in Patients with Psoriasis

Cited by 19 publications

References 40 publications

microRNA cluster MC‐let‐7a‐1~let‐7d promotes autophagy and apoptosis of glioma cells by down‐regulating STAT3

microRNA cluster MC‐let‐7a‐1~let‐7d promotes autophagy and apoptosis of glioma cells by down‐regulating STAT3

Psoriasis Treatment Changes the Expression Profile of Selected Caspases and their Regulatory MicroRNAs

Expression profiling of microRNAs in human bone tissue from postmenopausal women

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