Similar Datasets
Project description:Long intergenic non-coding RNA linc-SUMF1-2 mediates CFTR-associated transcriptional regulation in human airway epithelia
| PRJNA433382 | ENA
Project description:The volume and composition of a thin layer of liquid covering the airway surface defend the lung from inhaled pathogens and debris. Airway epithelia secrete Cl- into the airway surface liquid through cystic fibrosis transmembrane conductance regulator (CFTR) channels, thereby increasing the volume of airway surface liquid. The discovery that pulmonary ionocytes contain high levels of CFTR led us to predict that ionocytes drive secretion. However, we found the opposite. Elevating ionocyte abundance increased liquid absorption, whereas reducing ionocyte abundance increased secretion. In contrast to other airway epithelial cells, ionocytes contained barttin/Cl- channels in their basolateral membrane. Disrupting barttin/Cl- channel function impaired liquid absorption, and overexpressing barttin/Cl- channels increased absorption. Together, apical CFTR and basolateral barttin/Cl- channels provide an electrically conductive pathway for Cl- flow through ionocytes, and the transepithelial voltage generated by apical Na+ channels drives absorption. These findings indicate that ionocytes mediate liquid absorption, and secretory cells mediate liquid secretion. Segregating these counteracting activities to distinct cell types enables epithelia to precisely control the airway surface. Moreover, the divergent role of CFTR in ionocytes and secretory cells suggests that cystic fibrosis disrupts both liquid secretion and absorption.
| S-EPMC10575720 | biostudies-literature
Project description:Background: Long intergenic non-protein coding RNA 511 (LINC00511) is upregulated in diverse cancers and involved in prognosis. This study aimed to evaluate the prognostic profile of LINC00511 in cancer patients. Methods: Published studies evaluating the prognosis of LINC00511 in patients with different cancers were identified from Medline, Embase, and Web of Science. Analysis of the association between LINC00511 and clinicopathological characteristics was conducted. GEPIA was used to validation and functional analysis and LnCeVar was used to get genomic variations. Results: We eventually included 9 studies, and the combined results showed LINC00511 was significantly associated with decreased OS (HR = 3.18, 95% CI = 2.29 ~ 4.42, P < 0.001) albeit with mild heterogeneity (I 2 = 58.1%, P h = 0.014), similarly in cancer type subgroups: breast cancer, digestive system cancer, and cervical cancer (all P < 0.001). There is no publication bias and meta-regression indicated follow-up time maybe heterogeneity of the results (P = 0.008). Additionally, LINC00511 appeared to be correlated with age, clinical stage, tumor size, and lymph node metastasis. Those findings were confirmed in GEPIA. Through LnCeVars, gene ontology and functional pathways were enriched, and dysregulated hallmarks and related ceRNA network of LINC00511 were disturbed. Conclusions: LINC00511 could be predictive of poor OS and lymph node metastasis in multiple cancers, in another word, LINC00511 serves as an unfavorable prognostic factor, and its mechanism is related to ceRNA.
| S-EPMC7358593 | biostudies-literature
Project description:As a staple chemotherapy medicine, cisplatin (DDP) is extensively applied in cancer patients, but its drug resistance is limited. Numerous studies have elucidated that long non-coding RNA (lncRNA) performs as a pivotal agent in osteosarcoma (OS). Nevertheless, lncRNA long intergenic non-coding 00641 (LINC00641)'s functions in DDP resistance for OS remain obscure. The purpose of this study was to investigate the effect and mechanism of LINC00641 on drug resistance of OS. The tissues of both clinical cancer patients and the normal control were gathered. Detection of LINC00641, microRNA-320d (miR-320d) and myeloid cell leukemia-1 (MCL1) was conducted. After the selection of OS cell lines, the detection of cell advancement was applied. Series of experiments were conducted to verify the interaction of LINC00641, miR-320d and MCL1. Xenografted tumor model in vivo was utilized to determine the function of LINC00641. The data displayed, LINC00641 was prominently elevated in OS tissues and cells, especially in DDP-resistant tumors and cell lines. Knock-down LINC00641 was able to attenuate progression of DDP-resistant OS cells thus dampening their drug resistance toward DDP. Moreover, knock-downing LINC00641 gene was also able to manifest antagonism toward DDP-resistance in vivo. On the grounds of bioinformatics prediction, a direct binding of LINC00641 with miR-320d existed, whose target was MCL1. Meanwhile, LINC00641 modulated MCL1 via targeting miR-320d. Additionally, repressive LINC00641 blocked MCL1 via emulative interaction with miR-320d, thus expediting DDP-sensitivity of OS cells. All in all, it is found that LINC00641 is available to escalate drug resistance of DDP-resistant OS cells via mediation of miR-320d/MCL1 axis.
| S-EPMC9208475 | biostudies-literature
Project description:The genomic shock of whole-genome duplication (WGD) and hybridization introduces great variation into transcriptomes, for both coding and noncoding genes. An altered transcriptome provides a molecular basis for improving adaptation during the evolution of new species. The allotetraploid cotton, together with the putative diploid ancestor species compose a fine model for study the rapid gene neofunctionalization over the genome shock. Here we report on Drought-Associated Non-coding gene 1 (DAN1), a long intergenic noncoding RNA (lincRNA) that arose from the cotton progenitor A-diploid genome after hybridization and WGD events during cotton evolution. DAN1 in allotetraploid upland cotton (Gossypium hirsutum) is a drought-responsive lincRNA predominantly expressed in the nucleoplasm. Chromatin isolation by RNA purification profiling and electrophoretic mobility shift assay analysis demonstrated that GhDAN1 RNA can bind with DNA fragments containing AAAG motifs, similar to DNA binding with one zinc finger transcription factor binding sequences. The suppression of GhDAN1 mainly regulates genes with AAAG motifs in auxin-response pathways, which are associated with drought stress regulation. As a result, GhDAN1-silenced plants exhibit improved tolerance to drought stress. This phenotype resembles the drought-tolerant phenotype of the A-diploid cotton ancestor species, which has an undetectable expression of DAN1. The role of DAN1 in cotton evolution and drought tolerance regulation suggests that the genomic shock of interspecific hybridization and WGD stimulated neofunctionalization of non-coding genes during the natural evolutionary process.
| S-EPMC8331171 | biostudies-literature
Project description:Traditional pulmonary therapies for cystic fibrosis (CF) target the downstream effects of CF transmembrane conductance regulator (CFTR) dysfunction (the cause of CF). Use of one such therapy, ?-adrenergic bronchodilators (such as albuterol), is nearly universal for airway clearance. Conversely, novel modulator therapies restore function to select mutant CFTR proteins, offering a disease-modifying treatment. Recent trials of modulators targeting F508del-CFTR, the most common CFTR mutation, suggest that chronic ?-agonist use may undermine clinical modulator benefits. We therefore sought to understand the impact of chronic or excess ?-agonist exposure on CFTR activation in human airway epithelium. The present studies demonstrate a greater than 60% reduction in both wild-type and modulator-corrected F508del-CFTR activation following chronic exposure to short- and long-acting ?-agonists. This reduction was due to reduced cellular generation of cAMP downstream of the ?-2 adrenergic receptor-G protein complex. Our results point towards a posttranscriptional reduction in adenylyl cyclase function as the mechanism of impaired CFTR activation produced by prolonged ?-agonist exposure. ?-Agonist-induced CFTR dysfunction was sufficient to abrogate VX809/VX770 modulation of F508del-CFTR in vitro. Understanding the clinical relevance of our observations is critical for CF patients using these drugs, and for investigators to inform future CFTR modulator drug trials.
| S-EPMC5916247 | biostudies-literature
Project description:Transposable elements (TEs) are abundant in mammalian genomes and appear to have contributed to the evolution of their hosts by providing novel regulatory or coding sequences. We analyzed different regions of long intergenic non-coding RNA (lincRNA) genes in human and mouse genomes to systematically assess the potential contribution of TEs to the evolution of the structure and regulation of expression of lincRNA genes. Introns of lincRNA genes contain the highest percentage of TE-derived sequences (TES), followed by exons and then promoter regions although the density of TEs is not significantly different between exons and promoters. Higher frequencies of ancient TEs in promoters and exons compared to introns implies that many lincRNA genes emerged before the split of primates and rodents. The content of TES in lincRNA genes is substantially higher than that in protein-coding genes, especially in exons and promoter regions. A significant positive correlation was detected between the content of TEs and evolutionary rate of lincRNAs indicating that inserted TEs are preferentially fixed in fast-evolving lincRNA genes. These results are consistent with the repeat insertion domains of LncRNAs hypothesis under which TEs have substantially contributed to the origin, evolution, and, in particular, fast functional diversification, of lincRNA genes.
| S-EPMC4460805 | biostudies-other
Project description:The discovery that the mammalian transcriptome encodes thousands of long intergenic non-coding (linc) RNA transcripts, together with recent evidence that lincRNAs can regulate protein-coding genes, has added a new level of complexity to cellular transcriptional/translational regulation. Indeed several reports now link mutations in lincRNAs to heritable human disorders. Here, we identified a subset of lincRNAs in terminally differentiated adult human retinal neurons based on their sequence conservation across species. RNA sequencing of eye tissue from several mammalian species with varied rod/cone photoreceptor content identified 18 lincRNAs that were highly conserved across these species. Sixteen of the 18 were conserved in human retinal tissue with 14 of these also conserved in the macular region. A subset of lincRNAs exhibited restricted tissue expression profiles in mice, with preferential expression in the retina. Mouse models with different populations of retinal cells as well as in situ hybridization provided evidence that these lincRNAs localized to specific retinal compartments, most notably to the photoreceptor neuronal layer. Computational genomic loci and promoter region analyses provided a basis for regulated expression of these conserved lincRNAs in retinal post-mitotic neurons. This combined approach identified several lincRNAs that could be critical for retinal and visual maintenance in adults.
| S-EPMC3699063 | biostudies-literature
Project description:Long intergenic non-coding RNAs (lincRNAs) are transcribed from non-coding DNA sequences. Studies have revealed that aberrant expressions of lincRNAs are associated with various types of cancers and neurological disorders. Marek's disease (MD) is a highly contagious T-cell lymphoid neoplasia of chicken induced by Marek's disease virus (MDV). In this study, we first identified and validated linc-GALMD3 highly expressed in MDV-infected CD4+ T cells by RNA-Seq and qRT-PCR. By RNA-Seq analysis in MDCC-MSB1 cells after loss of function of linc-GALMD3 by shRNA, we found that linc-GALMD3 could positively cis-regulate its downstream gga-miR-223 gene expression. In contrast, it could trans-regulate the 748 differentially expressed genes (FDR < 0.01) that were mainly enriched into mitochondrial structure and cell cycle processes using GO analysis. Of these, the most significantly expressed gene EPYC might cause iris lesion in MD. The other eight genes, NDUFA4, NDUFB6, NDUFV1, NDUFS8, SDHB, UQCRC1, UQCRC2, and COX7A2, actively participated in oxidative phosphorylation in mitochondrial dysfunction and cell death. Most importantly, we found that the MDV replication was repressed when linc-GALMD3 was knocked down in CEF cells. Our results suggested that linc-GALMD3 might be a critical regulator in chicken MD and could be used as a candidate-promising mark for MD prevention, diagnosis, and treatment.
| S-EPMC5579197 | biostudies-literature
Project description:To identify functional lncRNAs in microglia-neurotropic virus interaction, high-throughput RNA sequencing was performed to obtain differential expressed lncRNAs (DELs) in microglia isolated from C57BL/6J mice, infected with or without neurotropic virus herpes simplex virus type 1 (HSV-1) (MOI 1 per group). All samples contain three mice’s microglia as a mixture given the isolated amount is low.
2021-10-03 | GSE167015 | GEO