RNA & disease (Houston, Tex.)最新文献

{"title":"Tumor-secreted microRNAs act as intercellular communication mediators to manipulate the host immune system","authors":"Yuan Yin, Xing Cai, Chen-Yu Zhang, Zhaohui Huang, Xi Chen","doi":"10.14800/RD.487","DOIUrl":"https://doi.org/10.14800/RD.487","url":null,"abstract":"Tumor cells influence their environment by releasing various substances such as cytokines and chemokines. Intensive studies over the past several years have demonstrated that microvesicles (MVs) secreted by tumor cells contain proteins, mRNAs, and microRNAs (miRNAs) that play important roles in intercellular crosstalk. We recently reported an exciting finding that tumor cells can actively manipulate the host immune response via secreting an important oncomir, miR-214, through a pathway involving MVs. As an extension of this finding, we showed that the delivery of miR-214 antisense oligonucleotides (ASOs) via MVs can significantly inhibit tumor-induced immune escape and tumor growth, which provides a novel, effective approach for tumor treatment.","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":"66657542","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-133α regulates neurotensin-associated colonic inflammation in colonic epithelial cells and experimental colitis.","authors":"Ivy Ka Man Law,&nbsp;Charalabos Pothoulakis","doi":"10.14800/rd.472","DOIUrl":"https://doi.org/10.14800/rd.472","url":null,"abstract":"<p><p>Ulcerative colitis (UC) and Crohn's Disease (CD) are the two most common forms of Inflammatory Bowel Diseases (IBD) marked by chronic and persistent inflammation. Neurotensin (NT), together with its receptor, NT receptor 1 (NTR1), are important mediators in intestinal inflammation and their expression is upregulated in the intestine of experimental colitis models and UC colonic biopsies. MicroRNAs (miRNAs) are short, non-coding RNA molecules which act as transcription repressors. We have previously shown that NT exposure upregulates miR-133α expression in human colonocytes NCM460 cells overexpressing NTR1 (NCM460-NTR1). Recently, miR-133α was further examined forits role in NT-associated proinflammatory signaling cascades and acute colitis <i>in vivo</i>. Our study shows that NT-induced miR-133α upregulation modulates NF-κB phosphorylation and promotes proinflammatory cytokine production. In addition, intracolonicinjection of antisense-miR-133α before colitis induction improves histological scores and proinflammatory cytokine transcription. More importantly, dysregulation of miR-133α levels and aftiphilin (AFTPH), a newly-identified miR-133α downstream target, is found only in UC patients, but not in patients with CD. Taken together, we identified NTR1/miR-133α/aftiphilin as a novel regulatory axis involved in NT-associated colonic inflammation in human colonocytes, acute colitis mouse model and in colonic biopsies from UC patients. Our results also provide evidence that colonic levels of NTR1, miR-133α and aftiphilin may also serve as potential biomarkers in UC.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4441413/pdf/nihms689406.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33332468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA and DNA nanoparticles for triggering RNA interference.","authors":"Ziad El Tannir, Kirill A Afonin, Bruce A Shapiro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Control over the delivery of different functionalities and their synchronized activation in vivo is a challenging undertaking that requires careful design and implementation. The goal of the research highlighted herein was to develop a platform allowing the simultaneous activation of multiple RNA interference pathways and other functionalities inside cells. Our team has developed several RNA, RNA/DNA and DNA/RNA nanoparticles able to successfully complete such tasks. The reported designs can potentially be used to target myriad of different diseases.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 Suppl 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301276/pdf/nihms-1723722.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39220692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The regulation of the p53/MDM2 feedback loop by microRNAs.","authors":"Cen Zhang,&nbsp;Juan Liu,&nbsp;Xiaolong Wang,&nbsp;Zhaohui Feng","doi":"10.14800/rd.502","DOIUrl":"https://doi.org/10.14800/rd.502","url":null,"abstract":"<p><p>Tumor suppressor p53 and its signaling pathway play a central role in tumor prevention. The E3 ubiquitin ligase MDM2, which is a direct p53 transcriptional target and also the most critical negative regulator of p53, forms an autoregulatory negative feedback loop with p53 in the cell to tightly regulate the levels and activity of p53. MicroRNAs (miRNAs) are endogenously expressed small non-coding RNAs that play a critical role in the post-translational regulation of gene expression. Recent studies have revealed that miRNAs directly regulate the levels of p53 or MDM2 to modulate the p53 function in tumor suppression. Recently, we identified miR-339-5p as a new miRNA that directly represses MDM2 to activate p53 and enhance p53 function in tumor suppression. Thus, miRNAs have become a new but important component of the p53 signaling pathway through regulating the p53/MDM2 feedback loop.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":"e502"},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4435570/pdf/nihms689453.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33322244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KRAS Cold Turkey: Using microRNAs to target KRAS-addicted cancer.","authors":"Matthew F Jones,&nbsp;Toshifumi Hara,&nbsp;Ashish Lal","doi":"10.14800/rd.539","DOIUrl":"https://doi.org/10.14800/rd.539","url":null,"abstract":"<p><p>Human cancers are driven by genetic mutations which cause aberrant activation of pro-growth pathways. Although cancers are uniquely dependent on the pro-growth signaling from oncogenic pathways, efforts to directly target these have been largely unsuccessful. One of the most common and drug resistant oncogenic drivers in colon cancer is the GTPase KRAS. It has been shown that colon cancers with KRAS driver mutations are also 'addicted' to proteins outside of the KRAS pathway due to aberrant re-wiring of cell signaling. A number of genes with a synthetic lethal relationship to mutant KRAS have been previously identified by RNAi screens. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, and their expression is frequently dysregulated in cancers. Recently, we have used an innovative functional miRNA screening approach to identify miRNAs that inhibit the survival of KRAS-mutant cells but not KRAS-wild-type cells. MiR-126 was one of the miRNAs that displayed this selective effect. We found that miR-126 induced synthetic lethality in KRAS-Mutant cells via the down-regulation of the polo-like kinase signaling network and a number of genes specifically necessary for the growth of KRAS-Mutant tumors. This study offers a new way forward for exploiting the regulatory power of miRNAs to specifically target aberrant cell signaling in cancer.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777587/pdf/nihms689455.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35765652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Gene Knockdown Efficiencies by Comparing siRNA-Loaded Cationic Nanogel Particles of Different Sizes","authors":"L. Nuhn","doi":"10.14800/RD.469","DOIUrl":"https://doi.org/10.14800/RD.469","url":null,"abstract":"In order to silence the expression levels of pathogenic genes, small interfering RNA (siRNA) requires a nano-sized carrier for its safe and stable delivery into cells. In this research highlight, we focus on well-defined cationic nanohydrogel particles developed in our group for such purposes. To investigate the nanogels’ mechanism for enhanced knockdown efficiencies, we recently synthesized two sets of particles with similar material composition and siRNA-loading characteristics, but – according to the manufacturing process – of different sizes. Within this study, 100-nm-sized nanogel particles loaded with siRNA accumulated inside the lysosomes already after 4 h and could not induce any gene knockdown, while 40-nm-sized particles were able to avoid lysosomal accumulation, and instead, generated moderate gene knockdown levels lasting for about three days. We believe that in analogy to other reports this size-dependent intracellular distribution behavior might be an essential key parameter for tuning the knockdown efficiency of the nanogel carriers. Moreover, these results might further contribute to the development of advanced siRNA carrier systems in order to enhance RNAi’s translation into the clinics.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657530","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":"Differentiation of adult mesenchymal stem cells into chondrogenic cells using small molecules or microRNA","authors":"Onju Ham, C. Lee, Ran Kim, J. Lee, Min Young Lee, Jongmin Kim, K. Hwang, Woochul Chang","doi":"10.14800/RD.458","DOIUrl":"https://doi.org/10.14800/RD.458","url":null,"abstract":"Transplantation of mesenchymal stem cells (MSCs) into osteoarthritis (OA) and rheumatoid arthritis (RA) patients has been studied as a therapeutic tool for regeneration of damaged cartilage. MSCs have several beneficial effects, including immunomodulatory activity, and release various paracrine factors. Despite their abundant beneficial effects, transplantation of naive MSCs is hampered by heterogeneous populations of differentiated and undifferentiated stem cells. However, transplantation of differentiated MSCs overcomes the problem of transplantation of naive MSCs. Thus, to repair damaged tissue, a therapeutic strategy based on the use of differentiated MSCs is needed to treat RA or OA patients. Here, we summarize methods that can regulate differentiation of MSCs into chondrocytes by small molecules or miRNAs, and suggest the capacity of patient tissue-derived MSCs as a therapeutic strategy for treatment of OA or RA patients.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657481","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":"Obesity-induced microRNAs and type 2 diabetes","authors":"Won-Mo Yang, Wan Lee","doi":"10.14800/RD.413","DOIUrl":"https://doi.org/10.14800/RD.413","url":null,"abstract":"Obesity is a growing health problem and causally linked to the pathogenesis of type 2 diabetes mellitus (T2DM). T2DM is a metabolic disorder caused by peripheral insulin resistance as well as suboptimal insulin production. Although endogenous non-coding small microRNAs (miRNAs) have been shown to play an important role in the post-transcriptional repression of target genes, the implication of obesity-induced miRNAs in metabolic disorders particularly in the development of insulin resistance is largely unknown. Recent studies have revealed that SFA palmitate and high fat diet (HFD) significantly increase the expression of certain miRNAs, such as miR-29a and miR-195, in myocytes and hepatocytes. These obesity-induced miRNAs are also up-regulated by saturated fatty acid (SFA) treatment in cultured myocytes and hepatocytes. miR-29a targets IRS-1 3’UTR directly and represses IRS-1 expression at the post-transcriptional level. The ectopic expression of miR-29a impairs insulin signaling and the insulin-stimulated glucose uptake in myocytes. miR-195 down-regulates the mRNA and protein expression of INSR without apparently changing IRS-1 expression in hepatocytes. The ectopic expression of miR-195 reduced significantly the insulin-stimulated phosphorylation of INSR and its downstream molecules in hepatocytes. Moreover, the ectopic expression of miR-195 reduced the insulin-stimulated synthesis of glycogen significantly. Taken together, these results clearly suggest that the induction of miR-29a and miR-195 by SFA are causally linked to the development of insulin resistance in obesity. These evidences provide novel insights into the molecular basis of insulin resistance, and implicate SFA-induced miRNAs in the development of T2DM and metabolic diseases.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"2 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657174","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 global expression analysis and genomic profiling of the camptothecin-resistant T-ALL derived cell line CPT-K5","authors":"Christopher Veigaard, E. Kjeldsen","doi":"10.14800/RD.441","DOIUrl":"https://doi.org/10.14800/RD.441","url":null,"abstract":"The clinical use of the camptothecin (CPT) derivatives, topotecan and irinotecan, has had a significant impact on cancer therapy. However, acquired clinical resistance to these drugs is common, which greatly hampers their clinical efficacy. MicroRNAs (miRNAs) is an exciting novel class of endogenous non-coding RNAs that negatively regulate gene expression of up to 50% of the protein-coding genes at the post-translational level. Abnormal expression of miRNAs is associated with pathogenesis of cancer and is also implicated in anticancer drug resistance phenotypes. We used global expression analysis to examine for differential miRNA expression between the camptothecin-resistant cell line CPT-K5 and its parental CPT-sensitive RPMI-8402. In the CPT-K5 cell line 18 miRNAs were deregulated. Fifteen of these were down-regulated and three were up-regulated. The miRNA-193a-3p, miR-130a-3p, and miR-29c-3p were the most down-regulated miRNAs at 205.9-fold, 33.9-fold and 5.5-fold, respectively, while the miRNA let-7i-5p was the most up-regulated at 3.9-fold. We used subtraction BAC-based array CGH analysis to examine for genomic copy number changes. Only for the three most down-regulated miRNAs a positive correlation was found with genomic loss of their chromosomal regions in which they are encoded. Potential functional targets of the differentially expressed miRNAs were examined by searching the miRBase and miRTarBase databases. Recurrent KEGG pathways that theoretically could be affected by the deregulated miRNAs are lysine degradation, cell cycle, PI3K-Akt-, ERbB- and p53- signaling pathways. We show that the intracellular levels of several miRNAs are significantly deregulated upon acquisition of CPT resistance in the T-ALL derived cell line CPT-K5, and that genomic copy number changes is not a major cause of deregulation. In addition, the most deregulated miRNAs in our study have previously been described to be involved in various types of chemotherapeutic resistance, including the chemotherapeutics CPT, gefitinib and cisplatin in other cancer and cell types. Our study adds to the current knowledge of the mechanisms of acquired CPT resistance. Specific miRNAs may prove to be future targets to reverse or inhibit development of CPT resistance thereby providing means for a more effective treatment.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657408","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-33a, an important marker and putative therapeutic target in chronic HBV-induced fibrosis","authors":"Chuan-Feng Huang, Cheng-chao Sun, Fang Zhao, Yadong Zhang, Dejia Li","doi":"10.14800/RD.416","DOIUrl":"https://doi.org/10.14800/RD.416","url":null,"abstract":"To investigate the roles and mechanisms of miR-33a in liver fibrosis, miR-33a expression in whole liver and serum samples was measured from chronic hepatitis B (CHB) patients by quantitative real-time PCR (qRT-PCR). In addition, Human and murine primary liver fibrosis-associated cells were isolated and treated with transforming growth factor-β1 (TGF-β1). We found that miR-33a expression levels in liver tissue significantly increased with a fibrosis progression manner in the human liver. Furthermore, serum miR-33a levels associated positively with progressing process of hepatic fibrosis. miR-33a was in particular increased in hepatic stellate cells (HSC) than other liver fibrosis-associated cells. Stimulation of HSCs with TGF-β1 leads to a critical increase of miR- 33a. Increasing miR-33a levels increased (whereas inhibiting miR-33a weakened) the activation role of TGF-β1 in LX-2 cells, which might be a potential mechanism through moderating Smad7 expression. Altogether, data suggest that miR-33a may be a novel marker for HSC activation and hepatic fibrosis progress, suggesting a new therapeutic target in liver fibrosis.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66657395","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}