RNA & disease (Houston, Tex.)最新文献

{"title":"The biological function of microRNA195 and its relationship with angiogenesis","authors":"Jingjing Wang, Q. Zeng, Caihong Yi, Jinjing Luo, Ningning Tang, Shao-Hua Wang, Jia Chen, K. Cao, Jianda Zhou","doi":"10.14800/RD.610","DOIUrl":"https://doi.org/10.14800/RD.610","url":null,"abstract":"MicroRNA participates in multiple biological activities by combining with target genes, degrading target mRNA or suppressing its translation which regulates the expression of genes. MicroRNA-195 is an important member of microRNA-15/161/195/424/497 family. miRNA-195 exerts its significant biological function in regulating cell cycle, apoptosis, cell metabolism, cell proliferation and metastasis by targetedly modulating MYB, CCND1, CCND3, CCNE1, E2F3, CDK6, Bcl-2, APP, BACE1, GLUT, SRC-3, Vav2, and CDC42. Recent studies have shown that miRNA-195 regulates angiogenic factors such as FGF1, VEGF and signaling pathways such as TGF-β1/ Smads and that miRNA-195 participates in the restoration of intima, tumour, the remodling of angiocarpy.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657299","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Widening HSF1 horizon: the microRNA connection","authors":"Srijit Das, N. Bhattacharyya","doi":"10.14800/RD.596","DOIUrl":"https://doi.org/10.14800/RD.596","url":null,"abstract":"Heat shock factor 1 (HSF1) is an evolutionary conserved transcription factor, which acts as protector of cellular proteome against adverse environmental conditions including increased temperature in eukaryotes. HSF1 positively regulates expression of a set of cytoprotective proteins popularly called as heat shock proteins (HSPs) as part of an adaptive mechanism of cells known as heat shock response (HSR). It has also been shown that apart from cellular stress response, HSF1 has the ability to regulate many other biological processes including aging, metabolism, development etc. This is primarily achieved by the ability of HSF1 to regulate expression of myriad of genes other than those coding for classical HSPs in presence and/or absence of stress. MicroRNAs (miRNAs) are short endogenous RNA molecules which can regulate many biological processes by acting as post-transcriptional regulators of gene expression. Altered expression of miRNAs in response to thermal stress has been reported in different species; however, the underlying mechanism remained elusive. We recently showed that HSF1 has the ability to regulate expression of miRNAs by binding to their upstream sequences and our result established hsa-miR-432 as the first HSF1-regulated miRNA.We therefore speculate that the landscape of HSF1 transcripts is much broader than it was earlier thought and includes HSF1-regulated miRNAs, the recently identified non-coding arm of HSF1 transcripts. The HSF1-regulated miRNAs have the potential to regulate many cellular events by acting as important downstream molecules of HSF1.Our finding thus uncovers a novel functional aspect of HSF1 with the emergence of hsa-miR-432 as a novel transcriptional target of HSF1.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Small RNAs inhibit bladder cancer by up-regulating tumor suppressor genes","authors":"Chenghe Wang, Zhong Chen, Z. Ye","doi":"10.14800/RD.595","DOIUrl":"https://doi.org/10.14800/RD.595","url":null,"abstract":"RNA activation (RNAa) is a newly discovered mechanism in which non-coding RNAs like small double-stranded RNAs (dsRNAs) or micro RNAs (miRNAs) induce sequence-specific gene activation by targeting promoter. Although its underlying mechanism remains unclear, we and others have demonstrated that Ago protein, RNA polymerase II (RNA Pol II) and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) are required for RNAa. In addition, RNAa is conserved in mammalian cells. Increasing evidences indicated that dsRNAs or miRNAs can induce tumor suppressing genes expression and hold great capacity to inhibit bladder cancer cells. RNAa provides a novel method for gene manipulation and offers an exciting potential for therapeutic modality against bladder cancers. In this review, we will focus on the research advances in exploiting the mechanism of RNAa and its applications in bladder cancer therapeutics.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA miR-124a, a negative regulator of insulin secretion, is hyperexpressed in human pancreatic islets of type 2 diabetic patients","authors":"G. Sebastiani, F. Mancarella, Giuliana Ventriglia, L. Nigi, Marco Valentini, G. Grieco, F. Dotta","doi":"10.14800/RD.593","DOIUrl":"https://doi.org/10.14800/RD.593","url":null,"abstract":"MicroRNAs are a class of negative regulators of gene expression, which have been demonstrated to be involved in the development of endocrine pancreas and in the regulation of insulin secretion. Type 2 Diabetes (T2D) is a metabolic disease characterized by insulin-resistance in target tissues and by the functional alteration of pancreatic insulin-secreting beta-cells. Recently, we characterized the expression levels of microRNAs miR-124a and miR-375, both involved in the control of beta cell function, in human pancreatic islets obtained from T2D and from age-matched non-diabetic organ donors. We observed the hyperexpression of miR-124a in human pancreatic islets obtained from T2D patients vs non-diabetic subjects, while miR-375 did not result differentially expressed. Moreover, we demonstrated that miR-124a overexpression in MIN6-pseudoislets reduced glucose-stimulated insulin secretion. Among predicted miR-124a target genes we focused on Foxa2 and Mtpn, which are both involved in the regulation of insulin secretion and of glucose sensing. Indeed, using luciferase assay, we validated miR-124a targeting Foxa2 and Mtpn 3’UTR sequences. Accordingly, upon miR-124a inhibition in MIN6 pseudoislets, we detected the upregulation of Foxa2 and Mtpn and of other selected miR-124a predicted target genes such as Akt3, Flot2, Sirt1, and NeuroD1, indicating a possible role for such a microRNA in the control of several beta-cell functions. In conclusion, we uncovered a major hyperexpression of miR-124a in T2D islets, whose silencing resulted in increased expression of target genes of major importance for beta cell function and whose overexpression impaired glucose stimulated insulin secretion, leading to the hypothesis that an altered miR-124a expression may contribute to beta cell dysfunction in type 2 diabetes","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel role of Na+,K+-ATPase ligands in regulating cytokines mRNA stability by HuR signalosome and the underlying pathophysiologic relevance","authors":"Yin Wu, C. Dan, Bian Jin-jun, Feng Su, Chen Wei, Zhou Ri, Ma Lin, H. Zi-chun","doi":"10.14800/RD.546","DOIUrl":"https://doi.org/10.14800/RD.546","url":null,"abstract":"Increasing evidence demonstrated that Na + ,K + -ATPase ligands, also called as cardiotonic steroids, are hormone-like immunoregulators, because endogenous Na + ,K + -ATPase ligands are frequently detected in inflammatory-related diseases, moreover, Na + ,K + -ATPase ligands regulate multiple aspects of immune responses. One of prominent roles of Na + ,K + -ATPase ligands in regulating immunity is their abilities of modulating cytokines expression. Na + ,K + -ATPase ligands can either upregulate or downregulate IL-1β, TNF-α, IL6, or iNOS expressions in different model system, however, all of those studies pointed to transcriptional upregulation. In our recent studies, we proposed for the first time that Na + ,K + -ATPase ligands are capable of regulating cytokines mRNA stability by integrating multiple posttranscriptional mechanisms, including human antigen R (HuR) translocation, generation of miR181s, and formation of stress granules. These mechanisms did not function alone, but act in a synergistic or an antagonistic manner to fine-tune the cytokines expression, HuR nuclear export, however, forms signalosome and plays a core role among these processes. By taking advantage of these posttranscriptional mechanisms, Na + ,K + -ATPase ligands stabilized cyclooxygenase-2 mRNA stability in lung epithelial cells and induced acute lung injury. In monocytes, ouabain-induced HuR export competed with miR181s on the shared target of TNF-α, also triggered stress granules formation and recruited TNF-α mRNA into it for protection, thereby stabilizing TNF-α mRNA and reversing sepsis-induced immunoparalysis, both in vitro and in vivo. Besides in immune-related diseases, HuR also regulated a variety of pro-oncogenes and anti-oncogenes expressions in cancer cells, which determined the cancer cells sensitivity towards Na + ,K + -ATPase ligands or other chemotherapeutic drugs. In sum, HuR emerges as a very important signaling molecule in Na + ,K + -ATPase ligands-mediated effects, which opens new avenues for understanding of the pathophysiologic and pharmacological activities of Na + ,K + -ATPase ligands. Identification of the components of HuR signalosome will offer more novel targets and biomarkers for diseases therapy.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging and systemic hormonal status affects the circulating miR-21, miR-146a and FasL levels","authors":"R. Kangas, E. Pöllänen, V. Kovanen","doi":"10.14800/RD.552","DOIUrl":"https://doi.org/10.14800/RD.552","url":null,"abstract":"MicroRNAs are small  molecules, found in all cell types and body fluids, which most commonly affect negatively to gene expressions by translational repression. Their role in various physiological conditions and diseases has been emphasized during the last twenty years. In our recent studies with postmenopausal monozygotic twin sisters (n=11), we have investigated how different systemic hormonal status affects the levels of specific circulating microRNAs and other molecules related to inflammation and apoptosis, both processes associated with aging. Our results have shown that the systemic levels of miR-21, miR-146a and Fas ligand are lower within the postmenopausal women who are using estrogen-based hormonal replacement (HRT), compared to their non-using co-twins (p=0.018, p=0.039, p=0.021, respectively). To strengthen the aging effect, we also measured the same markers from the premenopausal control women (n=8), with natural hormonal status, and found out that the inflammatory profile was healthier among the young women and that the serum miR-21 profile was more similar with the HRT users than non-users, and miR-146 and FasL profile more similar to non-users. These findings demonstrate that HRT has effects on the circulating inflammation related regulatory molecules. Whether we can state that the effects are clearly positive or negative, needs further investigations and understanding of the regulatory system.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Roles of miR-1, miR-133a, and miR-206 in calcium, oxidative stress, and NO signaling involved in muscle diseases","authors":"Y. Matsuzaka, K. Hashido","doi":"10.14800/RD.558","DOIUrl":"https://doi.org/10.14800/RD.558","url":null,"abstract":"MiR-1, miR-133a, and miR-206 are abundantly expressed in skeletal muscle and regulate the post-transcriptional expression of target genes. These miRNAs are upregulated in sera of DMD, BMD, LGMD, and FSHD patients, as well as mdx mice and CXMDj dogs, suggesting that the serum miRNAs may substitute for CK levels as be novel biomarkers for muscle disorders. These miRNAs are released into the extracellular environment in  vesicular structures called exosomes, by mechanisms that are regulated by calcium, oxidative stress, and NO signaling. In this review, we will highlight the relationship between calcium, oxidative stress, and NO signaling and the release of miRNAs via exosomes as well as discuss the functions of these miRNAs.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"miR-126 regulates angiogenesis by target vascular endothelial growth factor-A in gastric adenocarcinoma","authors":"Yupeng Lei, Hongxia Chen, F. Shi, Xiaodong Zhou","doi":"10.14800/RD.523","DOIUrl":"https://doi.org/10.14800/RD.523","url":null,"abstract":"miR-126 is an endothelial-specific microRNA essential for governing vascular integrity and angiogenesis. Its role in tumor angiogenesis of gastric cancer (GC) is unclear. This study aimed at determining the role of miR-126 in GC angiogenesis.  Down-regulation of miR-126 was found to inversely correlate with an increased microvessel density (MVD) and vascular endothelial growth factor A (VEGF-A) expression in gastric cancer tissues. Bioinformatics analysis and luciferase reporter assay revealed that miR-126 directly targeted the 3'-untranslated region (3'-UTR) of VEGF-A mRNA. In addition, the restoration of miR-126 expression by lentivirus-miR-126 (Lenti-miR-126) transfection obviously reduced the expression of VEGF-A and the activition of its downstream genes, Akt, mTOR and Erk1/2 in gastric cancer cell lines SGC-7901, MKN-28 and MKN-45. In contrast, the down-regulation of miR-126 expression by lentivirus-anti-miR-126 (Lenti-anti-miR-126) transfection obviously up-regulated the expression of VEGF-A and its downstream signaling pathways. In vivo xenograft mice model experiments clarified the down-regulation of VEGF-A and MVD as well as inhibition of tumor growth by up-regulation of miR-126. Overall, the results from our study suggested that miR-126 could suppress tumor growth and tumor angiogenesis of GC through VEGF-A signaling, and it is a novel potential therapeutic target for GC.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the role for miRNA in human leukemia","authors":"Niraj M. Shah, K. Bowles, S. Rushworth, D. MacEwan","doi":"10.14800/RD.540","DOIUrl":"https://doi.org/10.14800/RD.540","url":null,"abstract":"The biological function of short non-coding RNAs known as micro RNAs (miRNAs) is unravelling to uncover a complex arrangement within every cell whereby they modulate most cellular responses.  There has been much investigation as to the influence of miRNA on cell signalling processes and their cellular effects.  Moreover, recently miRNA have been implicated in both physiological responses, as well as having critical roles in a variety of diseased states.  The effects of these unique biochemical regulators are often subtle, but decisive with regards to a cell’s pathophysiology and disease.  Researchers have investigated both the regulation of signalling pathways by miRNA, but also the regulation of miRNA generation processes by signalling steps themselves.  There exists an interesting interrelationship whereby miRNA can reinforce a cell’s signalling effects.  Thus miRNA have a role in normal cell physiological functioning.  Aberrant miRNA generation would therefore lead to unruly signalling activity through which disease often results from such dysregulation.  We will review the roles for miRNA here with emphasis on their function in human leukemia.  Better understanding of these mechanisms that underlie pathologically-relevant signalling alterations that create cancer or are involved in cancer chemotherapy-resistance, will lead to better targeting and treatments for not only leukemia, but all relevant cancers.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"microRNAs and the Ebola Virus","authors":"Zheng Fu, Hongwei Liang, Ke Zen, Chen-Yu Zhang, Xi Chen","doi":"10.14800/RD.492","DOIUrl":"https://doi.org/10.14800/RD.492","url":null,"abstract":"We recently reported an interesting finding that the Ebola virus (EBOV) encodes functional microRNAs (miRNAs) that can be produced through the cellular miRNA processing machinery. In addition, the prediction of EBOV miRNA target genes provided some clues about the regulatory roles of EBOV miRNAs. In summary, our findings provide a basis for further assessing the roles of the EBOV miRNAs in viral infection and virus-host interactions.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}