{"title":"Bivalent aptamer-dual siRNA chimera is emerging as a new combination therapy","authors":"Hong Yan Liu","doi":"10.14800/RD.1534","DOIUrl":"https://doi.org/10.14800/RD.1534","url":null,"abstract":"The selective delivery of siRNAs in a cell type-specific manner represents the major challenge for the application of RNA interference for disease treatment. Aptamers have great potentials as carriers for tumor specific siRNA delivery. With the nature of nucleic acid, aptamers can be ease of modification and editing. Novel bivalent aptamer-dual siRNA chimera (PSMA aptamer- survivin siRNA -EGFR siRNA -PSMA aptamer, PSEP) was developed by fusing two siRNAs (specific to EGFR and survivin) between two PSMA aptamers. Bivalent aptamer offers increased siRNA internalization compared with monovalent counterpart. PSEP chimera is able to inhibit EGFR and survivin simultaneously in a cell type-specific manner. In PSMA expressing tumor xenografts, PSEP significantly inhibits tumor growth and angiogenesis. Our results highlight that co-delivery of multiple siRNAs with bivalent aptamer represents a novel approach for targeted combination therapy.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41761071","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}
W. Blalock, M. Piazzi, A. Gallo, A. Bavelloni, Enrico Focaccia, I. Faenza
{"title":"RNA processing and ribosome biogenesis in bone marrow failure dsorders","authors":"W. Blalock, M. Piazzi, A. Gallo, A. Bavelloni, Enrico Focaccia, I. Faenza","doi":"10.14800/RD.1531","DOIUrl":"https://doi.org/10.14800/RD.1531","url":null,"abstract":"Bone marrow failure disorders (BMFDs), which are characterized by an early pro-apoptotic phase which results in faulty hematopoiesis and anemia, more often than not progress to outright acute myelogenous leukemia (AML). Recent findings have indicated that most if not all of these disorders have a very significant RNA processing component to their pathology. This review aims to highlight some of normal processes of RNA metabolism that have been recently demonstrated to be altered in BMFDs.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42519302","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":"A possible link between specific transfer RNA methylation and tumorigenic phenotype of breast cancer","authors":"K. Tomita","doi":"10.14800/RD.1530","DOIUrl":"https://doi.org/10.14800/RD.1530","url":null,"abstract":"The human RNA methyltransferase BCDIN3D is overexpressed in breast cancer cells and involved in cellular invasion and poor prognosis of breast cancer. Several years ago, BCDIN3D was reported to dimethylate the 5'-monophosphate of specific precursor miRNAs (pre-miRNAs), such as the tumor suppressor miR145. Dimethylation of the 5'-monophosphate of the pre-miRNA negatively regulates the subsequent processing by Dicer in vitro , and results in the downregulated expression of the mature form of the miRNA. The depletion of BCDIN3D also reportedly results in the suppression of the tumorigenic phenotype of breast cancer cells. Thus, these findings suggested that BCDIN3D promotes the cellular invasion of breast cancer cells, by downregulating the expression of tumor suppressor miRNAs via the dimethylation of the 5'-monophosphate of the corresponding pre-miRNAs . Recently, we found that cytoplasmic tRNA His is actually the primary target of human BCDIN3D, rather than pre-miR145. BCDIN3D monomethylates the 5'-phosphate of cytoplasmic tRNA His much more efficiently than that of pre-miRNA in vitro , and is responsible for the monomethylation of the 5'-phosphate of cytoplasmic tRNA His in vivo . BCDIN3D recognizes the eight-nucleotide long extended acceptor helix with the G -1 -A 73 mis-pair at the top of the acceptor stem of tRNA His , which are exceptional features among cytoplasmic tRNA species. These results not only reveal the primary target of BCDIN3D, which is overexpressed in breast cancer cells, but also highlight the possible involvement of the 5'-phosphomethylation of tRNA and/or tRNA in the tumorigenesis of breast cancer cells, beyond its established function in protein synthesis.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41390687","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":"A novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in prostate cancer.","authors":"D. Das, O. Ogunwobi","doi":"10.14800/RD.1503","DOIUrl":"https://doi.org/10.14800/RD.1503","url":null,"abstract":"Prostate cancer (PCa) is the second most common cause of cancer-specific deaths in the U.S. Unfortunately, the underlying molecular mechanisms for its development and progression remain unclear. Studies have established that microRNAs (miRNAs) are dysregulated in PCa. The intron-derived microRNA-1207-3p (miR-1207-3p) is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, miR-1207-3p in PCa had not previously been investigated. Therefore, we explored if miR-1207-3p plays any regulatory role in PCa. We discovered that miR-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells, and that increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of fibronectin type III domain containing 1 (FNDC1). Our studies also revealed significant overexpression of FNDC1, fibronectin (FN1) and the androgen receptor (AR) in human PCa cell lines as well as tissues, and FNDC1, FN1, and AR positively correlate with aggressive PCa. These findings, recently published in Experimental Cell Research, are the first to describe a novel miR-1207-3p/FNDC1/FN1/AR novel regulatory pathway in PCa.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"4 1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46487406","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":"Technologies of high-throughput tissue-specific gene expression profiling","authors":"Zhichao Xu, Xiao Liu","doi":"10.14800/RD.1492","DOIUrl":"https://doi.org/10.14800/RD.1492","url":null,"abstract":"Gene expression profiling is an important strategy to study animal development, response to stimuli and diseases. RNAs measured in gene expression profiling experiments are frequently purified from mixture of multiple cell types. The resultant data have low resolution, incapable of distinguishing transcriptome of different cell types and likely biased towards up-regulated genes in dominant tissues. These problems can be solved by obtaining tissue-specific gene expression profile. For dozens of years, there have been several strategies developed to isolate specific tissues or purify RNAs from tissue of interest, and combined with high-throughput RNA assays to generate transcriptome of various specific tissues or cell types. This review will introduce basic principles of these methods and their application in large-scale transcriptome analysis, and discuss on their advantages and limitation.","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45957253","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":"A novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in prostate cancer.","authors":"Dibash K Das, Olorunseun O Ogunwobi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Prostate cancer (PCa) is the second most common cause of cancer-specific deaths in the U.S. Unfortunately, the underlying molecular mechanisms for its development and progression remain unclear. Studies have established that microRNAs (miRNAs) are dysregulated in PCa. The intron-derived microRNA-1207-3p (miR-1207-3p) is encoded at the non-protein coding gene locus <i>PVT1</i> on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, miR-1207-3p in PCa had not previously been investigated. Therefore, we explored if miR-1207-3p plays any regulatory role in PCa. We discovered that miR-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells, and that increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of fibronectin type III domain containing 1 (FNDC1). Our studies also revealed significant overexpression of FNDC1, fibronectin (FN1) and the androgen receptor (AR) in human PCa cell lines as well as tissues, and FNDC1, FN1, and AR positively correlate with aggressive PCa. These findings, recently published in Experimental Cell Research, are the first to describe a novel miR-1207-3p/FNDC1/FN1/AR novel regulatory pathway in PCa.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5328418/pdf/nihms850185.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34776054","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":"microRNA-29 mediates a novel negative feedback loop to regulate SCAP/SREBP-1 and lipid metabolism.","authors":"Peng Ru, Deliang Guo","doi":"10.14800/rd.1525","DOIUrl":"https://doi.org/10.14800/rd.1525","url":null,"abstract":"<p><p>The membrane-bound transcription factors, SREBPs (sterol regulatory element-binding proteins), play a central role in regulating lipid metabolism. The transcriptional activation of SREBPs requires the key protein SCAP (SREBP-cleavage activating protein) to translocate their precursors from the endoplasmic reticulum to the Golgi for subsequent proteolytic activation, a process tightly regulated by a cholesterol-mediated negative feedback loop. Our previous work showed that the SCAP/SREBP-1 pathway is significantly upregulated in human glioblastoma (GBM), the most deadly brain cancer, and that glucose-mediated <i>N</i>-glycosylation of SCAP is a prerequisite step for SCAP/SREBP trafficking. More recently, we demonstrated that microRNA-29 (miR-29) mediates a previously unrecognized negative feedback loop in SCAP/SREBP-1 signaling to control lipid metabolism. We found that SREBP-1, functioning as a transcription factor, promotes the expression of the miR-29 family members, miR-29a, -29b and -29c. In turn, the miR-29 isoforms reversely repress the expression of SCAP and SREBP-1. Moreover, treatment with miR-29 mimics effectively suppressed GBM tumor growth by inhibiting SCAP/SREBP-1 and <i>de novo</i> lipid synthesis. These findings, recently published in <i>Cell Reports</i>, strongly suggest that delivery of miR-29 <i>in vivo</i> may be a promising approach to treat cancer and metabolic diseases by suppressing SCAP/SREBP-1-regulated lipid metabolism.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"4 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485916/pdf/nihms861933.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35131129","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}
Justin Halman, Emily Satterwhite, Jaclyn Smollett, Eckart Bindewald, Lorena Parlea, Mathias Viard, Paul Zakrevsky, Wojciech K Kasprzak, Kirill A Afonin, Bruce A Shapiro
{"title":"Triggerable RNA nanodevices.","authors":"Justin Halman, Emily Satterwhite, Jaclyn Smollett, Eckart Bindewald, Lorena Parlea, Mathias Viard, Paul Zakrevsky, Wojciech K Kasprzak, Kirill A Afonin, Bruce A Shapiro","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The targeted and conditional activation of pharmaceuticals is an increasingly important feature in modern personalized medicine. Nucleic acid nanoparticles show tremendous potential in this exploit due to their programmability and biocompatibility. Among the most powerful nucleic acid specific treatments is RNA interference-based therapeutics. RNA interference is a naturally occurring phenomenon in which specific genes are effectively silenced. Recently we have developed two different strategies based on customized multivalent nucleic acid nanoparticles with the ability to conditionally activate RNA interference in diseased cells as well as elicit detectable fluorescent responses.[1,2] These novel technologies can be further utilized for the simultaneous delivery and conditional intracellular activation of multiple therapeutic and biosensing functions to combat various diseases.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"4 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8301261/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39225473","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}
William J Jaremko, Zhen Huang, Wei Wen, Andrew Wu, Nicholas Karl, Li Niu
{"title":"One aptamer, two functions: the full-length aptamer inhibits AMPA receptors, while the short one inhibits both AMPA and kainate receptors.","authors":"William J Jaremko, Zhen Huang, Wei Wen, Andrew Wu, Nicholas Karl, Li Niu","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>AMPA and kainate receptors, along with NMDA receptors, are distinct subtypes of glutamate ion channels. Excessive activity of AMPA and kainate receptors has been implicated in neurological diseases, such as epilepsy and neuropathic pain. Antagonists that block their activities are therefore potential drug candidates. In a recent article in the <i>Journal of Biological Chemistry</i> by Jaremko <i>et al</i>. 2017, we have reported on the discovery and molecular characterization of an RNA aptamer of a dual functionality: the full-length RNA (101 nucleotide) inhibits AMPA receptors while the truncated or the short (55 nucleotide) RNA inhibits both the AMPA and kainate receptors. The full-length RNA aptamer was isolated through a specially designed, systematic evolution of ligands by exponential enrichment (SELEX) using only a single type of AMPA receptors expressed in HEK-293 cells. The design feature and the results of our recent article are highlighted here, as they demonstrate the utility of the SELEX approach and the potential of using a single AMPA receptor type to develop potent, novel RNA aptamers targeting multiple subunits and AMPA/kainate receptor subtypes with length-dependent functionalities.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5553901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35320042","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 miR-125a and miR-320c are potential tumor suppressor microRNAs epigenetically silenced by the polycomb repressive complex 2 in multiple myeloma.","authors":"Mohammad Alzrigat, Helena Jernberg-Wiklund","doi":"10.14800/rd.1529","DOIUrl":"https://doi.org/10.14800/rd.1529","url":null,"abstract":"<p><p>We have previously presented the histone methyltransferase enhancer of zeste homolog 2 (EZH2) of the polycomb repressive complex 2 (PRC2) as a potential therapeutic target in Multiple Myeloma (MM). In a recent article in Oncotarget by Alzrigat. <i>et al</i>. 2017, we have reported on the novel finding that EZH2 inhibition using the highly selective inhibitor of EZH2 enzymatic activity, UNC1999, reactivated the expression of microRNA genes previously reported to be underexpressed in MM. Among these, we have identified miR-125a-3p and miR-320c as potential tumor suppressor microRNAs as they were predicted to target MM-associated oncogenes; IRF-4, XBP-1 and BLIMP-1. We also found EZH2 inhibition to reactivate the expression of miR-494, a previously reported regulator of the c-MYC oncogene. In addition, we could report that EZH2 inhibition downregulated the expression of a few well described oncogenic microRNAs in MM. The data from our recent article are here highlighted as it shed a new light onto the oncogenic function of the PRC2 in MM. These data further strengthen the notion that the PRC2 complex may be of potential therapeutic interest.</p>","PeriodicalId":90965,"journal":{"name":"RNA & disease (Houston, Tex.)","volume":"4 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5485917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35131130","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}