Browsing by Subject "lncRNA"

Now showing 1 - 7 of 7
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    AZI23'UTR Is a New SLC6A3 Downregulator Associated with an Epistatic Protection Against Substance Use Disorders
    (Springer Nature, 2018-07) Liu, Kefu; Yu, Jinlong; Zhao, Juan; Zhou, Yanhong; Xiong, Nian; Xu, Jie; Wang, Tao; Bell, Richard L.; Qing, Hong; Lin, Zhicheng; Psychiatry, School of Medicine
    Regulated activity of SLC6A3, which encodes the human dopamine transporter (DAT), contributes to diseases such as substance abuse disorders (SUDs); however, the exact transcription mechanism remains poorly understood. Here, we used a common genetic variant of the gene, intron 1 DNP1B sequence, as bait to screen and clone a new transcriptional activity, AZI23'UTR, for SLC6A3. AZI23'UTR is a 3' untranslated region (3'UTR) of the human 5-Azacytidine Induced 2 gene (AZI2) but appeared to be transcribed independently of AZI2. Found to be present in both human cell nuclei and dopamine neurons, this RNA was shown to downregulate promoter activity through a variant-dependent mechanism in vitro. Both reduced RNA density ratio of AZI23'UTR/AZI2 and increased DAT mRNA levels were found in ethanol-naive alcohol-preferring rats. Secondary analysis of dbGaP GWAS datasets (Genome-Wide Association Studies based on the database of Genotypes and Phenotypes) revealed significant interactions between regions upstream of AZI23'UTR and SLC6A3 in SUDs. Jointly, our data suggest that AZI23'UTR confers variant-dependent transcriptional regulation of SLC6A3, a potential risk factor for SUDs.
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    The EGLN-HIF O2-Sensing System: Multiple Inputs and Feedbacks
    (Cell Press, 2017-06-15) Ivan, Mircea; Kaelin, William G., Jr.; Medicine, School of Medicine
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    A long non-coding RNA protects the heart from pathological hypertrophy
    (Nature Publishing Group, 2014-10-02) Han, Pei; Li, Wei; Lin, Chiou-Hong; Yang, Jin; Shang, Ching; Nuernberg, Sylvia T.; Jin, Kevin Kai; Xu, Weihong; Lin, Chieh-Yu; Lin, Chien-Jung; Xiong, Yiqin; Chien, Huanchieh; Zhou, Bin; Ashley, Euan; Bernstein, Daniel; Chen, Peng-Sheng; Chen, Huei-sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin; Department of Medicine, IU School of Medicine
    The role of long noncoding RNA (lncRNA) in adult hearts is unknown
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    Long non-coding RNAs in renal cell carcinoma: A systematic review and clinical implications
    (Impact Journals, 2017-04-12) Li, Ming; Wang, Ying; Cheng, Liang; Niu, Wanting; Zhao, Guoan; Raju, Jithin K.; Huo, Jun; Wu, Bin; Yin, Bo; Song, Yongsheng; Bu, Renge; Pathology and Laboratory Medicine, School of Medicine
    Renal cell carcinoma is one of the most common malignancy in adults, its prognosis is poor in an advanced stage and early detection is difficult due to the lack of molecular biomarkers. The identification of novel biomarkers for RCC is an urgent and meaningful project. Long non-coding RNA (lncRNA) is transcribed from genomic regions with a minimum length of 200 bases and limited protein-coding potential. Recently, lncRNAs have been greatly studied in a variety of cancer types. They participate in a wide variety of biological processes including cancer biology. In this review, we provide a new insight of the profiling of lncRNAs in RCC and their roles in renal carcinogenesis, with an emphasize on their potential in diagnosis, prognosis and potential roles in RCC therapy.
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    Rare variants in long non-coding RNAs are associated with blood lipid levels in the TOPMed Whole Genome Sequencing Study
    (medRxiv, 2023-06-29) Wang, Yuxuan; Selvaraj, Margaret Sunitha; Li, Xihao; Li, Zilin; Holdcraft, Jacob A.; Arnett, Donna K.; Bis, Joshua C.; Blangero, John; Boerwinkle, Eric; Bowden, Donald W.; Cade, Brian E.; Carlson, Jenna C.; Carson, April P.; Chen, Yii-Der Ida; Curran, Joanne E.; de Vries, Paul S.; Dutcher, Susan K.; Ellinor, Patrick T.; Floyd, James S.; Fornage, Myriam; Freedman, Barry I.; Gabriel, Stacey; Germer, Soren; Gibbs, Richard A.; Guo, Xiuqing; He, Jiang; Heard-Costa, Nancy; Hildalgo, Bertha; Hou, Lifang; Irvin, Marguerite R.; Joehanes, Roby; Kaplan, Robert C.; Kardia, Sharon Lr.; Kelly, Tanika N.; Kim, Ryan; Kooperberg, Charles; Kral, Brian G.; Levy, Daniel; Li, Changwei; Liu, Chunyu; Lloyd-Jone, Don; Loos, Ruth Jf.; Mahaney, Michael C.; Martin, Lisa W.; Mathias, Rasika A.; Minster, Ryan L.; Mitchell, Braxton D.; Montasser, May E.; Morrison, Alanna C.; Murabito, Joanne M.; Naseri, Take; O'Connell, Jeffrey R.; Palmer, Nicholette D.; Preuss, Michael H.; Psaty, Bruce M.; Raffield, Laura M.; Rao, Dabeeru C.; Redline, Susan; Reiner, Alexander P.; Rich, Stephen S.; Ruepena, Muagututi'a Sefuiva; Sheu, Wayne H-H; Smith, Jennifer A.; Smith, Albert; Tiwari, Hemant K.; Tsai, Michael Y.; Viaud-Martinez, Karine A.; Wang, Zhe; Yanek, Lisa R.; Zhao, Wei; NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium; Rotter, Jerome I.; Lin, Xihong; Natarajan, Pradeep; Peloso, Gina M.; Biostatistics and Health Data Science, School of Medicine
    Long non-coding RNAs (lncRNAs) are known to perform important regulatory functions. Large-scale whole genome sequencing (WGS) studies and new statistical methods for variant set tests now provide an opportunity to assess the associations between rare variants in lncRNA genes and complex traits across the genome. In this study, we used high-coverage WGS from 66,329 participants of diverse ancestries with blood lipid levels (LDL-C, HDL-C, TC, and TG) in the National Heart, Lung, and Blood Institute (NHLBI) Trans-Omics for Precision Medicine (TOPMed) program to investigate the role of lncRNAs in lipid variability. We aggregated rare variants for 165,375 lncRNA genes based on their genomic locations and conducted rare variant aggregate association tests using the STAAR (variant-Set Test for Association using Annotation infoRmation) framework. We performed STAAR conditional analysis adjusting for common variants in known lipid GWAS loci and rare coding variants in nearby protein coding genes. Our analyses revealed 83 rare lncRNA variant sets significantly associated with blood lipid levels, all of which were located in known lipid GWAS loci (in a ±500 kb window of a Global Lipids Genetics Consortium index variant). Notably, 61 out of 83 signals (73%) were conditionally independent of common regulatory variations and rare protein coding variations at the same loci. We replicated 34 out of 61 (56%) conditionally independent associations using the independent UK Biobank WGS data. Our results expand the genetic architecture of blood lipids to rare variants in lncRNA, implicating new therapeutic opportunities.
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    Regulatory miRNAs and lncRNAs in Skin Cancer: A Narrative Review
    (MDPI, 2023-08-06) Natarelli, Nicole; Boby, Aleena; Aflatooni, Shaliz; Tran, Jasmine Thuy; Diaz, Michael Joseph; Taneja, Kamil; Forouzandeh, Mahtab; Medicine, School of Medicine
    Non-coding RNAs (ncRNAs) have a significant regulatory role in the pathogenesis of skin cancer, despite the fact that protein-coding genes have generally been the focus of research efforts in the field. We comment on the actions of long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) in the current review with an eye toward potential therapeutic treatments. LncRNAs are remarkably adaptable, acting as scaffolding, guides, or decoys to modify key signaling pathways (i.e., the Wnt/β-catenin pathway) and gene expression. As post-transcriptional gatekeepers, miRNAs control gene expression by attaching to messenger RNAs and causing their degradation or suppression during translation. Cell cycle regulation, cellular differentiation, and immunological responses are all affected by the dysregulation of miRNAs observed in skin cancer. NcRNAs also show promise as diagnostic biomarkers and prognostic indicators. Unraveling the complexity of the regulatory networks governed by ncRNAs in skin cancer offers unprecedented opportunities for groundbreaking targeted therapies, revolutionizing the landscape of dermatologic care.
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    Targeting Bim via a lncRNA Morrbid Regulates the Survival of Preleukemic and Leukemic Cells
    (Elsevier, 2020-06-23) Cai, Zhigang; Aguilera, Fabiola; Ramdas, Baskar; Daulatabad, Swapna Vidhur; Srivastava, Rajneesh; Kotzin, Jonathan J.; Carroll, Martin; Wertheim, Gerald; Williams, Adam; Janga, Sarath Chandra; Zhang, Chi; Henao-Mejia, Jorge; Kapur, Reuben; Pediatrics, School of Medicine
    Inhibition of anti-apoptotic proteins BCL-2 and MCL-1 to release pro-apoptotic protein BIM and reactivate cell death could potentially be an efficient strategy for the treatment of leukemia. Here, we show that a lncRNA, MORRBID, a selective transcriptional repressor of BIM, is overexpressed in human acute myeloid leukemia (AML), which is associated with poor overall survival. In both human and animal models, MORRBID hyperactivation correlates with two recurrent AML drivers, TET2 and FLT3ITD. Mice with individual mutations of Tet2 or Flt3ITD develop features of chronic myelomonocytic leukemia (CMML) and myeloproliferative neoplasm (MPN), respectively, and combined presence results in AML. We observe increased levels of Morrbid in murine models of CMML, MPN, and AML. Functionally, loss of Morrbid in these models induces increased expression of Bim and cell death in immature and mature myeloid cells, which results in reduced infiltration of leukemic cells in tissues and prolongs the survival of AML mice.