https://scholars.lib.ntu.edu.tw/handle/123456789/452397
Title: | Different effects of long noncoding RNA NDRG1-OT1 fragments on NDRG1 transcription in breast cancer cells under hypoxia | Authors: | Yeh, C.-C. Luo, J.-L. Nhut Phan, N. Cheng, Y.-C. LU-PING CHOW MONG-HSUN TSAI ERIC YAO-YU CHUANG LIANG-CHUAN LAI |
Issue Date: | 2018 | Publisher: | Taylor and Francis Inc. | Journal Volume: | 15 | Journal Issue: | 12 | Start page/Pages: | 1487-1498 | Source: | RNA Biology | Abstract: | Hypoxia plays a crucial role in the aggressiveness of solid tumors by driving multiple signaling pathways. Recently, long non-coding RNA (lncRNA) has been reported to promote or inhibit tumor aggressiveness by regulating gene expression. Previous studies in our laboratory found that the lncRNA NDRG1-OT1 is significantly up-regulated under hypoxia and inhibits its target gene NDRG1 at both the mRNA and protein levels. At the protein level, NDRG1-OT1 increases NDRG1 degradation via ubiquitin-mediated proteolysis. However, the repressive mechanism of NDRG1 at the RNA level is still unknown. Therefore, the purpose of this study was to study how NDRG1-OT1 transcriptionally regulates its target gene NDRG1. Luciferase reporter assays showed that NDRG1-OT1 decreased NDRG1 promoter activities. Mass spectrometry, bioinformatics tools, genetic manipulation, and immunoblotting were used to identify the interacting proteins. Surprisingly, different fragments of NDRG1-OT1?had opposite effects on NDRG1. The first quarter fragment (1–149 nt) of NDRG1-OT1 had no effect on the NDRG1 promoter; the second quarter fragment (150–263 nt) repressed NDRG1 by increasing the binding affinity of HNRNPA1; the third quarter fragment (264–392 nt) improved NDRG1 promoter activity by recruiting HIF-1α; the fourth quarter fragment (393–508 nt) down-regulated NDRG1 promoter activity via down-regulation of KHSRP under hypoxia. In summary, we have found a novel mechanism by which different fragments of the same lncRNA can cause opposite effects within the same target gene. ? 2018, ? 2018 Informa UK Limited, trading as Taylor & Francis Group. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85058080510&doi=10.1080%2f15476286.2018.1553480&partnerID=40&md5=66a77ce2eea011b2c625e836f896690c https://scholars.lib.ntu.edu.tw/handle/123456789/452397 |
ISSN: | 15476286 | DOI: | 10.1080/15476286.2018.1553480 | SDG/Keyword: | heterogeneous nuclear ribonucleoprotein A1; hypoxia inducible factor 1alpha; long untranslated RNA; cell cycle protein; HIF1A protein, human; hypoxia inducible factor 1alpha; KHSRP protein, human; long untranslated RNA; N-myc downstream-regulated gene 1 protein; protein binding; RNA binding protein; signal peptide; transactivator protein; Article; binding affinity; bioinformatics; breast cancer; cancer cell; controlled study; down regulation; embryo; gene; genetic manipulation; genetic transcription; HEK293T cell line; human; human cell; immunoblotting; luciferase assay; mass spectrometry; MCF-7 cell line; n myc downstream regulated gene 1; overlapping transcript 1; promoter region; transcription regulation; tumor hypoxia; breast tumor; chemistry; conformation; female; gene expression regulation; genetics; hypoxia; metabolism; reporter gene; tumor cell line; Breast Neoplasms; Cell Cycle Proteins; Cell Line, Tumor; Female; Gene Expression Regulation, Neoplastic; Genes, Reporter; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Intracellular Signaling Peptides and Proteins; Nucleic Acid Conformation; Promoter Regions, Genetic; Protein Binding; RNA, Long Noncoding; RNA-Binding Proteins; Trans-Activators; Transcription, Genetic |
Appears in Collections: | 生物化學暨分子生物學科研究所 |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.