{"title":"T2DB: A Web Database for Long Non-Coding RNA Genes in Type II Diabetes.","authors":"Rebecca Distefano, Mirolyuba Ilieva, Jens Hedelund Madsen, Hideshi Ishii, Masanori Aikawa, Sarah Rennie, Shizuka Uchida","doi":"10.3390/ncrna9030030","DOIUrl":"10.3390/ncrna9030030","url":null,"abstract":"<p><p>Type II diabetes (T2D) is a growing health problem worldwide due to increased levels of obesity and can lead to other life-threatening diseases, such as cardiovascular and kidney diseases. As the number of individuals diagnosed with T2D rises, there is an urgent need to understand the pathogenesis of the disease in order to prevent further harm to the body caused by elevated blood glucose levels. Recent advances in long non-coding RNA (lncRNA) research may provide insights into the pathogenesis of T2D. Although lncRNAs can be readily detected in RNA sequencing (RNA-seq) data, most published datasets of T2D patients compared to healthy donors focus only on protein-coding genes, leaving lncRNAs to be undiscovered and understudied. To address this knowledge gap, we performed a secondary analysis of published RNA-seq data of T2D patients and of patients with related health complications to systematically analyze the expression changes of lncRNA genes in relation to the protein-coding genes. Since immune cells play important roles in T2D, we conducted loss-of-function experiments to provide functional data on the T2D-related lncRNA <i>USP30-AS1</i>, using an in vitro model of pro-inflammatory macrophage activation. To facilitate lncRNA research in T2D, we developed a web application, T2DB, to provide a one-stop-shop for expression profiling of protein-coding and lncRNA genes in T2D patients compared to healthy donors or subjects without T2D.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 3","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204529/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9516155","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}
Non-Coding RNAPub Date : 2023-04-18DOI: 10.3390/ncrna9020028
Patrick K T Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K DiStefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P Gerber, He Lin, Simon J Conn, Doha Magdy Mostafa Sleem, Lisa Timmons
{"title":"The <i>Non-Coding RNA</i> Journal Club: Highlights on Recent Papers-12.","authors":"Patrick K T Shiu, Mirolyuba Ilieva, Anja Holm, Shizuka Uchida, Johanna K DiStefano, Agnieszka Bronisz, Ling Yang, Yoh Asahi, Ajay Goel, Liuqing Yang, Ashok Nuthanakanti, Alexander Serganov, Suresh K Alahari, Chunru Lin, Barbara Pardini, Alessio Naccarati, Jing Jin, Beshoy Armanios, Xiao-Bo Zhong, Nikolaos Sideris, Salih Bayraktar, Leandro Castellano, André P Gerber, He Lin, Simon J Conn, Doha Magdy Mostafa Sleem, Lisa Timmons","doi":"10.3390/ncrna9020028","DOIUrl":"10.3390/ncrna9020028","url":null,"abstract":"<p><p>We are delighted to share with you our twelfth Journal Club and highlight some of the most interesting papers published recently [...].</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10144170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9697856","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 Cystic Fibrosis Transmembrane Conductance Regulator Gene (CFTR) Is under Post-Transcriptional Control of microRNAs: Analysis of the Effects of agomiRNAs Mimicking miR-145-5p, miR-101-3p, and miR-335-5p.","authors":"Chiara Papi, Jessica Gasparello, Matteo Zurlo, Lucia Carmela Cosenza, Roberto Gambari, Alessia Finotti","doi":"10.3390/ncrna9020029","DOIUrl":"https://doi.org/10.3390/ncrna9020029","url":null,"abstract":"<p><p>(1) Background: MicroRNAs are involved in the expression of the gene encoding the chloride channel CFTR (Cystic Fibrosis Transmembrane Conductance Regulator); the objective of this short report is to study the effects of the treatment of bronchial epithelial Calu-3 cells with molecules mimicking the activity of pre-miR-145-5p, pre-miR-335-5p, and pre-miR-101-3p, and to discuss possible translational applications of these molecules in pre-clinical studies focusing on the development of protocols of possible interest in therapy; (2) Methods: <i>CFTR</i> mRNA was quantified by Reverse Transcription quantitative Polymerase Chain Reaction (RT-qPCR). The production of the CFTR protein was assessed by Western blotting; (3) Results: The treatment of Calu-3 cells with agomiR-145-5p caused the highest inhibition of <i>CFTR</i> mRNA accumulation and CFTR production; (4) Conclusions: The treatment of target cells with the agomiR pre-miR-145-5p should be considered when <i>CFTR</i> gene expression should be inhibited in pathological conditions, such as polycystic kidney disease (PKD), some types of cancer, cholera, and SARS-CoV-2 infection.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10146138/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9374581","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}
Non-Coding RNAPub Date : 2023-04-13DOI: 10.3390/ncrna9020026
Latika Matai, Frank J Slack
{"title":"MicroRNAs in Age-Related Proteostasis and Stress Responses.","authors":"Latika Matai, Frank J Slack","doi":"10.3390/ncrna9020026","DOIUrl":"https://doi.org/10.3390/ncrna9020026","url":null,"abstract":"<p><p>Aging is associated with the accumulation of damaged and misfolded proteins through a decline in the protein homeostasis (proteostasis) machinery, leading to various age-associated protein misfolding diseases such as Huntington's or Parkinson's. The efficiency of cellular stress response pathways also weakens with age, further contributing to the failure to maintain proteostasis. MicroRNAs (miRNAs or miRs) are a class of small, non-coding RNAs (ncRNAs) that bind target messenger RNAs at their 3'UTR, resulting in the post-transcriptional repression of gene expression. From the discovery of aging roles for <i>lin-4</i> in <i>C. elegans,</i> the role of numerous miRNAs in controlling the aging process has been uncovered in different organisms. Recent studies have also shown that miRNAs regulate different components of proteostasis machinery as well as cellular response pathways to proteotoxic stress, some of which are very important during aging or in age-related pathologies. Here, we present a review of these findings, highlighting the role of individual miRNAs in age-associated protein folding and degradation across different organisms. We also broadly summarize the relationships between miRNAs and organelle-specific stress response pathways during aging and in various age-associated diseases.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143298/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10096647","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":"Targeting miRNAs and Other Non-Coding RNAs as a Therapeutic Approach: An Update.","authors":"Emine Bayraktar, Recep Bayraktar, Hulya Oztatlici, Gabriel Lopez-Berestein, Paola Amero, Cristian Rodriguez-Aguayo","doi":"10.3390/ncrna9020027","DOIUrl":"10.3390/ncrna9020027","url":null,"abstract":"<p><p>Since the discovery of the first microRNAs (miRNAs, miRs), the understanding of miRNA biology has expanded substantially. miRNAs are involved and described as master regulators of the major hallmarks of cancer, including cell differentiation, proliferation, survival, the cell cycle, invasion, and metastasis. Experimental data indicate that cancer phenotypes can be modified by targeting miRNA expression, and because miRNAs act as tumor suppressors or oncogenes (oncomiRs), they have emerged as attractive tools and, more importantly, as a new class of targets for drug development in cancer therapeutics. With the use of miRNA mimics or molecules targeting miRNAs (i.e., small-molecule inhibitors such as anti-miRS), these therapeutics have shown promise in preclinical settings. Some miRNA-targeted therapeutics have been extended to clinical development, such as the mimic of miRNA-34 for treating cancer. Here, we discuss insights into the role of miRNAs and other non-coding RNAs in tumorigenesis and resistance and summarize some recent successful systemic delivery approaches and recent developments in miRNAs as targets for anticancer drug development. Furthermore, we provide a comprehensive overview of mimics and inhibitors that are in clinical trials and finally a list of clinical trials based on miRNAs.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10145226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9369368","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":"LncRNA PNKY Is Upregulated in Breast Cancer and Promotes Cell Proliferation and EMT in Breast Cancer Cells.","authors":"Forough Hakiminia, Firooz Jannat Alipoor, Mostafa Keshavarz, Malek Hossein Asadi","doi":"10.3390/ncrna9020025","DOIUrl":"https://doi.org/10.3390/ncrna9020025","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) are known to be important regulators in different cellular processes and are implicated in various human diseases. Recently, lncRNA PNKY has been found to be involved in pluripotency and differentiation of embryonic and postnatal neural stem cells (NSCs); however, its expression and function in cancer cells is still unclear. In the present study, we observed the expression of PNKY in various cancer tissues, including brain, breast, colorectal, and prostate cancers. In particular, we demonstrated that lncRNA PNKY was significantly upregulated in breast tumors, especially high-grade tumors. Knock down experiments indicated that the suppression of PNKY in breast cancer cells could restrict their proliferation by promoting apoptosis, senescence, and cell cycle disruption. Moreover, the results demonstrated that PNKY may play a crucial role in the cell migration of breast cancer cells. We further found that PNKY may trigger EMT in breast cancer cells by upregulating miR-150 and restricting the expression of Zeb1 and Snail. This study is the first to provide new evidence on the expression and biological function of PNKY in cancer cells and its potential contribution to tumor growth and metastasis.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10143469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9361241","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}
Non-Coding RNAPub Date : 2023-04-01DOI: 10.3390/ncrna9020024
Adaysha C Williams, Vaishali Singh, Pengyuan Liu, Alison J Kriegel
{"title":"Liquid Biopsies Poorly miRror Renal Ischemia-Reperfusion Injury.","authors":"Adaysha C Williams, Vaishali Singh, Pengyuan Liu, Alison J Kriegel","doi":"10.3390/ncrna9020024","DOIUrl":"https://doi.org/10.3390/ncrna9020024","url":null,"abstract":"<p><p>Acute kidney injury (AKI) is the rapid reduction in renal function. It is often difficult to detect at an early stage. Biofluid microRNAs (miRs) have been proposed as novel biomarkers due to their regulatory role in renal pathophysiology. The goal of this study was to determine the overlap in AKI miRNA profiles in the renal cortex, urine, and plasma samples collected from a rat model of ischemia-reperfusion (IR)-induced AKI. Bilateral renal ischemia was induced by clamping the renal pedicles for 30 min, followed by reperfusion. Urine was then collected over 24 h, followed by terminal blood and tissue collection for small RNA profiling. Differentially expressed (IR vs. sham) miRs within the urine and renal cortex sample types demonstrated a strong correlation in normalized abundance regardless of injury (IR and sham: R<sup>2</sup> = 0.8710 and 0.9716, respectively). Relatively few miRs were differentially expressed in multiple samples. Further, there were no differentially expressed miRs with clinically relevant sequence conservation common between renal cortex and urine samples. This project highlights the need for a comprehensive analysis of potential miR biomarkers, including analysis of pathological tissues and biofluids, with the goal of identifying the cellular origin of altered miRs. Analysis at earlier timepoints is needed to further evaluate clinical potential.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9425912","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":"CircRNAs and RNA-Binding Proteins Involved in the Pathogenesis of Cancers or Central Nervous System Disorders.","authors":"Yuka Ikeda, Sae Morikawa, Moeka Nakashima, Sayuri Yoshikawa, Kurumi Taniguchi, Haruka Sawamura, Naoko Suga, Ai Tsuji, Satoru Matsuda","doi":"10.3390/ncrna9020023","DOIUrl":"10.3390/ncrna9020023","url":null,"abstract":"<p><p>Circular RNAs (circRNAs), a newly recognized group of noncoding RNA transcripts, have established widespread attention due to their regulatory role in cell signaling. They are covalently closed noncoding RNAs that form a loop, and are typically generated during the splicing of precursor RNAs. CircRNAs are key post-transcriptional and post-translational regulators of gene expression programs that might influence cellular response and/or function. In particular, circRNAs have been considered to function as sponges of specific miRNA, regulating cellular processes at the post-transcription stage. Accumulating evidence has shown that the aberrant expression of circRNAs could play a key role in the pathogenesis of several diseases. Notably, circRNAs, microRNAs, and several RNA-binding proteins, including the antiproliferative (APRO) family proteins, could be indispensable gene modulators, which might be strongly linked to the occurrence of diseases. In addition, circRNAs have attracted general interest for their stability, abundance in the brain, and their capability to cross the blood-brain barrier. Here, we present the current findings and theragnostic potentials of circRNAs in several diseases. With this, we aim to provide new insights to support the development of novel diagnostic and/or therapeutic strategies for these diseases.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10142617/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9425911","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}
Non-Coding RNAPub Date : 2023-03-30DOI: 10.3390/ncrna9020022
Tatiana Pavlovna Shkurat, Manar Ammar, Olga Bocharova, Elena Teplyakova, Anzhela Aleksandrova, Ruba Ali, Leonard Lipovich
{"title":"The Role of Genetic Variants in the Long Non-Coding RNA Genes <i>MALAT1</i> and <i>H19</i> in the Pathogenesis of Childhood Obesity.","authors":"Tatiana Pavlovna Shkurat, Manar Ammar, Olga Bocharova, Elena Teplyakova, Anzhela Aleksandrova, Ruba Ali, Leonard Lipovich","doi":"10.3390/ncrna9020022","DOIUrl":"https://doi.org/10.3390/ncrna9020022","url":null,"abstract":"<p><p>Long non-coding RNAs (lncRNAs) play important roles in the maintenance of metabolic homeostasis. Recently, many studies have suggested that lncRNAs, such as Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and Imprinted Maternally Expressed Transcript (H19), might participate in the pathogenesis of metabolic disorders such as obesity. We conducted a case-control study with 150 Russian children and adolescents aged between 5 and 17 years old in order to assess the statistical association between the single nucleotide polymorphisms (SNPs) rs3200401 in <i>MALAT1</i> and rs217727 in <i>H19</i>, and the risk of developing obesity in this population. We further explored the possible association of rs3200401 and rs217727 with BMI Z-score and insulin resistance. The <i>MALAT1</i> rs3200401 and <i>H19</i> rs217727 SNPs were genotyped using Taqman SNP genotyping assay. The <i>MALAT1</i> rs3200401 SNP was identified as a risk factor for childhood obesity (<i>p <</i> 0.05) under the dominant and allelic models, and the CT heterozygous genotype was associated with the risk of increased BMI and with insulin resistance. The <i>H19</i> rs217727 SNP had no significant association with obesity risk (all <i>p ></i> 0.05). Our findings thus suggest that <i>MALAT1</i> SNP rs3200401 is a potential indicator of obesity susceptibility and pathogenesis in children and adolescents.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-03-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10141382/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9425913","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}
Non-Coding RNAPub Date : 2023-03-22DOI: 10.3390/ncrna9020021
Martin R Ramos-Gonzalez, Eduardo Vazquez-Garza, Gerardo Garcia-Rivas, Cristian Rodriguez-Aguayo, Arturo Chavez-Reyes
{"title":"Therapeutic Effects of WT1 Silencing via Respiratory Administration of Neutral DOPC Liposomal-siRNA in a Lung Metastasis Melanoma Murine Model.","authors":"Martin R Ramos-Gonzalez, Eduardo Vazquez-Garza, Gerardo Garcia-Rivas, Cristian Rodriguez-Aguayo, Arturo Chavez-Reyes","doi":"10.3390/ncrna9020021","DOIUrl":"https://doi.org/10.3390/ncrna9020021","url":null,"abstract":"<p><p>The lungs represent a frequent target for metastatic melanoma as they offer a high-oxygen environment for tumor development. The overexpression of the WT1 protein has been associated with the occurrence of melanoma. In this study, we evaluated the effects of silencing the WT1 protein by siRNA in both in vitro in the B16F10 melanoma cell line and in vivo in a murine model of lung metastatic melanoma. We did this by implementing a novel respiratory delivery strategy of a neutral DOPC liposomal-siRNA system (L-siRNA). In vitro studies showed an effective silencing of the WT1 protein in the siRNAs' WT1-treated cells when compared with controls, resulting in a loss of the cell's viability and proliferation by inducing G1 arrest, the inhibition of the migration and invasion capacities of the cells, as well as the induction of apoptosis. In vivo, the respiratory administration of L-WT1 siRNA showed an efficient biodistribution on the lungs. After two weeks of treatment, the silencing of the WT1 protein resulted in an important antitumor activity that reduced the tumor weight. In the survival study, L-WT1 treatment could significantly delay the death of the animals. This work demonstrates the efficacy of the L-siRNA respiratory administration as a novel therapy to reduce pulmonary tumors and to increase survivability by silencing specific cancer oncogenes as WT1.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 2","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10037624/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9554276","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}