Non-Coding RNA最新文献

{"title":"Altered Expression of Vitamin D Metabolism Genes and Circulating MicroRNAs in PBMCs of Patients with Type 1 Diabetes: Their Association with Vitamin D Status and Ongoing Islet Autoimmunity.","authors":"Hakeemah Al-Nakhle,&nbsp;Ihsan Mohsen,&nbsp;Bashir Elnaem,&nbsp;Abdullah Alharbi,&nbsp;Ibtisam Alnakhli,&nbsp;Shareefa Almoarfi,&nbsp;Jameela Fallatah","doi":"10.3390/ncrna9050060","DOIUrl":"10.3390/ncrna9050060","url":null,"abstract":"<p><strong>Background: </strong>The immunomodulatory role of 1,25-Dihydroxy vitamin D3 (1,25(OH)2D3) is exerted through its interaction with the vitamin D receptor (VDR) present on pancreatic and immune cells. While a deficiency in vitamin D has been linked to Type 1 Diabetes Mellitus (T1DM), the exact molecular mechanism driving this down-regulation in T1DM is yet to be fully understood. This study aimed to decipher differences in the expression of genes associated with vitamin D metabolism in T1DM patients and to ascertain if there is a correlation between serum 1,25(OH)2D3 levels and the expression of these genes. We also sought to understand the influence of specific microRNAs (miRNAs) on the expression of vitamin D metabolism genes in peripheral blood mononuclear cells (PBMCs) of T1DM patients. Furthermore, the study delved into the potential implications of altered vitamin D metabolism genes and miRNAs on autoimmune processes.</p><p><strong>Methods: </strong>Utilizing real-time PCR, we assessed the expression profiles of genes encoding for 1-hydroxylases (<i>CYP27B1</i>) and 24-hydroxylases (<i>CYP24A1</i>), as well as related miRNAs, in PBMCs from 30 T1DM patients and 23 healthy controls. ELISA tests facilitated the measurement of 1,25(OH)2D3, GAD65, and IA-2 levels.</p><p><strong>Results: </strong>Our findings showcased downregulated <i>CYP27B1</i> mRNA levels, while <i>CYP24A1</i> expression remained stable compared to healthy subjects (<i>CYP27B1</i>, <i>p</i> = 0.0005; <i>CYP24A1</i>, <i>p</i> = 0.205, respectively). In T1DM patients, the levels of has-miR-216b-5p were found to be increased, while the levels of has-miR-21-5p were decreased in comparison to the control group. Notably, no correlation was identified between the expression of <i>CYP27B1</i> in T1DM patients and the levels of has-miR-216b-5p, has-miR-21-5p, and 1,25(OH)2D3. A significant negative correlation was identified between <i>CYP27B1</i> mRNA levels in PBMCs of T1DM and IA2, but not with GAD65.</p><p><strong>Conclusions: </strong>The study highlights there were reduced levels of both <i>CYP27B1</i> mRNA and has-miR-21-5p, along with elevated levels of has-miR-216b-5p in the PBMCs of T1DM. However, the absence of a correlation between the expression of <i>CYP27B1</i>, levels of has-miR-216b-5p, and the status of 1,25(OH)2D3 suggests the possible existence of other regulatory mechanisms. Additionally, the inverse relationship between IA2 autoantibodies and <i>CYP27B1</i> expression in T1DM patients indicates a potential connection between this gene and the autoimmune processes inherent in T1DM.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230334","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":"Inverse Modulation of Aurora Kinase A and Topoisomerase IIα in Normal and Tumor Breast Cells upon Knockdown of Mitochondrial ASncmtRNA.","authors":"Maximiliano F Bendek,&nbsp;Christopher Fitzpatrick,&nbsp;Emanuel Jeldes,&nbsp;Anne Boland,&nbsp;Jean-François Deleuze,&nbsp;Nicole Farfán,&nbsp;Jaime Villegas,&nbsp;Gino Nardocci,&nbsp;Martín Montecino,&nbsp;Luis O Burzio,&nbsp;Verónica A Burzio","doi":"10.3390/ncrna9050059","DOIUrl":"10.3390/ncrna9050059","url":null,"abstract":"<p><p>Breast cancer is currently the most diagnosed form of cancer and the leading cause of death by cancer among females worldwide. We described the family of long non-coding mitochondrial RNAs (ncmtRNAs), comprised of sense (SncmtRNA) and antisense (ASncmtRNA) members. Knockdown of ASncmtRNAs using antisense oligonucleotides (ASOs) induces proliferative arrest and apoptotic death of tumor cells, but not normal cells, from various tissue origins. In order to study the mechanisms underlying this selectivity, in this study we performed RNAseq in MDA-MB-231 breast cancer cells transfected with ASncmtRNA-specific ASO or control-ASO, or left untransfected. Bioinformatic analysis yielded several differentially expressed cell-cycle-related genes, from which we selected Aurora kinase A (<i>AURKA</i>) and topoisomerase IIα (<i>TOP2A</i>) for RT-qPCR and western blot validation in MDA-MB-231 and MCF7 breast cancer cells, as well as normal breast epithelial cells (HMEC). We observed no clear differences regarding mRNA levels but both proteins were downregulated in tumor cells and upregulated in normal cells. Since these proteins play a role in genomic integrity, this inverse effect of ASncmtRNA knockdown could account for tumor cell downfall whilst protecting normal cells, suggesting this approach could be used for genomic protection under cancer treatment regimens or other scenarios.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230237","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 Intergenic Type LncRNA (LINC RNA) Faces in Cancer with In Silico Scope and a Directed Lens to LINC00511: A Step toward ncRNA Precision.","authors":"Shorouk Eldash,&nbsp;Eman F Sanad,&nbsp;Dina Nada,&nbsp;Nadia M Hamdy","doi":"10.3390/ncrna9050058","DOIUrl":"10.3390/ncrna9050058","url":null,"abstract":"<p><strong>Background: </strong>Long intergenic non-coding RNA, is one type of lncRNA, exerting various cellular activities, as does ncRNA, including the regulation of gene expression and chromatin remodeling. The abnormal expression of lincRNAs can induce or suppress carcinogenesis.</p><p><strong>Main body: </strong>LincRNAs can regulate cancer progression through different mechanisms and are considered as potential drug targets. Genetic variations such as single nucleotide polymorphisms (SNPs) in lincRNAs may affect gene expression and messenger ribonucleic acid (mRNA) stability. SNPs in lincRNAs have been found to be associated with different types of cancer, as well. Specifically, LINC00511 has been known to promote the progression of multiple malignancies such as breast cancer, colorectal cancer, lung cancer, hepatocellular carcinoma, and others, making it a promising cancer prognostic molecular marker.</p><p><strong>Conclusion: </strong>LincRNAs have been proved to be associated with different cancer types through various pathways. Herein, we performed a comprehensive literature and in silico databases search listing lncRNAs, lincRNAs including LINC00511, lncRNAs' SNPs, as well as LINC00511 SNPs in different cancer types, focusing on their role in various cancer types and mechanism(s) of action.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10610215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230238","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":"Discovery and Comprehensive Characterization of Novel Circular RNAs of the Apoptosis-Related <i>BOK</i> Gene in Human Ovarian and Prostate Cancer Cells, Using Nanopore Sequencing.","authors":"Christos K Kontos, Despina Hadjichambi, Maria Papatsirou, Paraskevi Karousi, Spyridon Christodoulou, Diamantis C Sideris, Andreas Scorilas","doi":"10.3390/ncrna9050057","DOIUrl":"10.3390/ncrna9050057","url":null,"abstract":"<p><p>CircRNAs have become a novel scientific research hotspot, and an increasing number of studies have shed light on their involvement in malignant progression. Prompted by the apparent scientific gap in circRNAs from apoptosis-related genes, such as <i>BOK</i>, we focused on the identification of novel <i>BOK</i> circRNAs in human ovarian and prostate cancer cells. Total RNA was extracted from ovarian and prostate cancer cell lines and reversely transcribed using random hexamer primers. A series of PCR assays utilizing gene-specific divergent primers were carried out. Next, third-generation sequencing based on nanopore technology followed by extensive bioinformatics analysis led to the discovery of 23 novel circRNAs. These novel circRNAs consist of both exonic and intronic regions of the <i>BOK</i> gene. Interestingly, the exons that form the back-splice junction were truncated in most circRNAs, and multiple back-splice sites were found for each <i>BOK</i> exon. Moreover, several <i>BOK</i> circRNAs are predicted to sponge microRNAs with a key role in reproductive cancers, while the presence of putative open reading frames indicates their translational potential. Overall, this study suggests that distinct alternative splicing events lead to the production of novel <i>BOK</i> circRNAs, which could come into play in the molecular landscape and clinical investigation of ovarian and prostate cancer.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":3.6,"publicationDate":"2023-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10609399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"54230336","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":"Long Non-Coding RNA TUG1 Gene Polymorphism and TUG1 Expression Level as Molecular Biomarkers of Systemic Lupus Erythematosus and Lupus Nephritis.","authors":"Gehan Abd-Elfatah Tawfeek,&nbsp;Heba Kasem,&nbsp;Eman Ali Abdallah,&nbsp;Mohammed Almulhim,&nbsp;Abdullah Almulhim,&nbsp;Mohammed Albarqi,&nbsp;Khaled Mohamed Amin Elzorkany","doi":"10.3390/ncrna9050056","DOIUrl":"https://doi.org/10.3390/ncrna9050056","url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA) TUG1 acts as a proto-oncogene, allowing the proliferation of tumor cells, and it has been related to inflammation. Therefore, we aimed in this study to investigate for the first time the role of TUG1 gene polymorphism and the TUG1 level as biomarkers in systemic lupus erythematosus (SLE) and their link to lupus nephritis 145 SLE. A total of 145 healthy controls were subjected to clinical and laboratory evaluation. The disease activity was assessed by the SLE disease activity index (SLEDAI) score. SLE patients were divided into two subgroups according to the presence of lupus nephritis. The TUG1 gene polymorphisms rs5749201 and rs886471 were determined by Sanger sequencing, and TUG1 expression was assessed by qRT-PCR. There was a significant increase in the risk of SLE AA, TA, dominant genotypes, and the A allele of rs5749201 (<i>p</i> < 0.001) by 4.9-, 10.1-, 6.5-, and 2.5-fold in comparison to the relative control. GG and TG, dominant genotypes and the G allele of rs886471 (<i>p</i> < 0.01) increased the risk by 5.09-, 11.9-, 6.5-, and 2.6-fold. AA, A allele, dominant and recessive rs5749201genotypes increased the risk of lupus nephritis by 16.6-, 7.4-, 7.1-, and 12.2-fold, respectively (<i>p</i> < 0.05). GG, dominant and recessive genotypes, and the G allele of rs886471 increased the risk of lupus nephritis by 17.04-, 7.8-, 9.4-, and 6.08-fold, respectively (<i>p</i> < 0.05). Additionally, the AG haplotype increased the risk of SLE and lupus nephritis by 2.7- and 7.8-fold, respectively. The AA rs5749201 and GG rs886471 variants are significantly associated with more severe disease (<i>p</i> < 0.001). TUG1 expression was significantly higher in SLE than in the control and in the lupus nephritis than in non-lupus nephritis cases (<i>p</i> < 0.05). Interestingly, AA rs5749201 and GG rs886471 were significantly associated with higher TUG1 levels (<i>p</i> < 0.001). It was also found that AA rs5749201 and high SLEDAI were predictors of lupus nephritis. Overall, our findings illustrated for the first time that TUG1 gene rs5749201 and rs886471 variants were associated with increased risk of SLE, more severe disease, and lupus nephritis, and the TUG1 level could be used as a diagnostic biomarker of SLE and lupus nephritis.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168042","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":"Novel Insights into Circular RNAs in Metastasis in Breast Cancer: An Update.","authors":"Paola Zepeda-Enríquez,&nbsp;Macrina B Silva-Cázares,&nbsp;César López-Camarillo","doi":"10.3390/ncrna9050055","DOIUrl":"https://doi.org/10.3390/ncrna9050055","url":null,"abstract":"<p><p>Circular RNAs (circRNAs) are single-stranded closed non-coding RNA molecules that are aberrantly expressed and produce tumor-specific gene signatures in human cancers. They exert biological functions by acting as transcriptional regulators, microRNA sponges, and protein scaffolds, regulating the formation of protein-RNA complexes and, ultimately, regulating gene expression. Triple-negative breast cancer (TNBC) is one of the most aggressive cancers of the mammary gland and has a poor prognosis. Studies of circRNAs in TNBC are limited but have demonstrated these molecules' pivotal roles in cell proliferation, invasion, metastasis, and resistance to chemo/radiotherapy, suggesting that they could be potential prognostic biomarkers and novel therapeutic targets. Here, we reviewed the status of actual knowledge about circRNA biogenesis and functions and summarized novel findings regarding their roles in TNBC development and progression. In addition, we discussed recent data about the importance of exosomes in the transport and export of circRNAs in TNBC. Deep knowledge of circRNA functions in metastasis and therapy responses could be an invaluable guide in the identification of novel therapeutic targets for advancing the treatment of TNBC.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41129201","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":"Extracellular microRNAs in Relation to Weight Loss-A Systematic Review and Meta-Analysis.","authors":"Camilla H B Veie,&nbsp;Isabella M T Nielsen,&nbsp;Nanna L S Frisk,&nbsp;Louise T Dalgaard","doi":"10.3390/ncrna9050053","DOIUrl":"https://doi.org/10.3390/ncrna9050053","url":null,"abstract":"<p><p>Obesity is an important risk factor for cardiovascular disease and type 2 diabetes mellitus. Even a modest weight loss of 5-15% improves metabolic health, but circulating markers to indicate weight loss efficiency are lacking. MicroRNAs, small non-coding post-transcriptional regulators of gene expression, are secreted from tissues into the circulation and may be potential biomarkers for metabolic health. However, it is not known which specific microRNA species are reproducibly changed in levels by weight loss. In this study, we performed a systematic review and meta-analysis to investigate the microRNAs associated with weight loss by comparing baseline to follow-up levels following intervention-driven weight loss. This systematic review was performed according to the PRISMA guidelines with searches in PubMed and SCOPUS. The primary search resulted in a total of 697 articles, which were screened according to the prior established inclusion and exclusion criteria. Following the screening of articles, the review was based on the inclusion of 27 full-text articles, which were evaluated for quality and the risk of bias. We performed systematic data extraction, whereafter the relative values for miRNAs were calculated. A meta-analysis was performed for the miRNA species investigated in three or more studies: miR-26a, miR-126, and miR-223 were overall significantly increased following weight loss, while miR-142 was significantly decreased after weight loss. miR-221, miR-140, miR-122, and miR-146 were not significantly changed by intervention-driven weight loss. These results indicate that few miRNAs are significantly changed during weight loss.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41168041","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 Potential microRNA Prognostic Signature in HNSCCs: A Systematic Review.","authors":"Mario Dioguardi,&nbsp;Francesca Spirito,&nbsp;Giovanna Iacovelli,&nbsp;Diego Sovereto,&nbsp;Enrica Laneve,&nbsp;Luigi Laino,&nbsp;Giorgia Apollonia Caloro,&nbsp;Ari Qadir Nabi,&nbsp;Andrea Ballini,&nbsp;Lorenzo Lo Muzio,&nbsp;Giuseppe Troiano","doi":"10.3390/ncrna9050054","DOIUrl":"https://doi.org/10.3390/ncrna9050054","url":null,"abstract":"<p><p>Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as \"signature microRNA OR miR\" AND \"HNSCC OR LSCC OR OSCC OR oral cancer\" were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41151831","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":"Inverse-Folding Design of Yeast Telomerase RNA Increases Activity In Vitro.","authors":"Kevin J Lebo,&nbsp;David C Zappulla","doi":"10.3390/ncrna9050051","DOIUrl":"https://doi.org/10.3390/ncrna9050051","url":null,"abstract":"<p><p><i>Saccharomyces cerevisiae</i> telomerase RNA, TLC1, is an 1157 nt non-coding RNA that functions as both a template for DNA synthesis and a flexible scaffold for telomerase RNP holoenzyme protein subunits. The tractable budding yeast system has provided landmark discoveries about telomere biology in vivo, but yeast telomerase research has been hampered by the fact that the large TLC1 RNA subunit does not support robust telomerase activity in vitro. In contrast, 155-500 nt miniaturized TLC1 alleles comprising the catalytic core domain and lacking the RNA's long arms do reconstitute robust activity. We hypothesized that full-length TLC1 is prone to misfolding in vitro. To create a full-length yeast telomerase RNA, predicted to fold into its biologically relevant structure, we took an inverse RNA-folding approach, changing 59 nucleotides predicted to increase the energetic favorability of folding into the modeled native structure based on the <i>p-num</i> feature of <i>Mfold</i> software. The sequence changes lowered the predicted ∆G of this \"determined-arm\" allele, DA-TLC1, by 61 kcal/mol (-19%) compared to wild-type. We tested DA-TLC1 for reconstituted activity and found it to be ~5-fold more robust than wild-type TLC1, suggesting that the inverse-folding design indeed improved folding in vitro into a catalytically active conformation. We also tested if DA-TLC1 functions in vivo, discovering that it complements a <i>tlc1</i>∆ strain, allowing cells to avoid senescence and maintain telomeres of nearly wild-type length. However, all inverse-designed RNAs that we tested had reduced abundance in vivo. In particular, inverse-designing nearly all of the Ku arm caused a profound reduction in telomerase RNA abundance in the cell and very short telomeres. Overall, these results show that the inverse design of <i>S. cerevisiae</i> telomerase RNA increases activity in vitro, while reducing abundance in vivo. This study provides a biochemically and biologically tested approach to inverse-design RNAs using <i>Mfold</i> that could be useful for controlling RNA structure in basic research and biomedicine.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514824/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143676","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":"Non-Coding RNAs: Foes or Friends for Targeting Tumor Microenvironment.","authors":"Anna Szymanowska,&nbsp;Cristian Rodriguez-Aguayo,&nbsp;Gabriel Lopez-Berestein,&nbsp;Paola Amero","doi":"10.3390/ncrna9050052","DOIUrl":"https://doi.org/10.3390/ncrna9050052","url":null,"abstract":"<p><p>Non-coding RNAs (ncRNAs) are a group of molecules critical for cell development and growth regulation. They are key regulators of important cellular pathways in the tumor microenvironment. To analyze ncRNAs in the tumor microenvironment, the use of RNA sequencing technology has revolutionized the field. The advancement of this technique has broadened our understanding of the molecular biology of cancer, presenting abundant possibilities for the exploration of novel biomarkers for cancer treatment. In this review, we will summarize recent achievements in understanding the complex role of ncRNA in the tumor microenvironment, we will report the latest studies on the tumor microenvironment using RNA sequencing, and we will discuss the potential use of ncRNAs as therapeutics for the treatment of cancer.</p>","PeriodicalId":19271,"journal":{"name":"Non-Coding RNA","volume":"9 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2023-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10514839/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143334","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}