NORAD, non-coding RNA activated by DNA damage, has a critical role in maintaining genomic stability.
non-coding RNA activated by DNA damage
NORAD is a highly abundant(expressed at 500‐1000 copies per cell), conserved mammalian noncoding RNA induced by DNA damage. Deletion of this lncRNA induces chromosomal instability and aneuploidy.
NORAD produces a 5.3 kb transcript that does not overlap other genes, starts from a single strong promoter overlapping a CpG island, terminates with a single major canonical poly(A) site, but is unspliced. Unlike most lncRNAs,it contains at least 12 structured repeated units and highly conserved consensus binding sites for an RNA-binding protein (RBP), and that is required for proper regulation of the RBP targets at physiological levels .
NORAD is upregulated in many cancers, including breast cancer, esophageal squamous cell carcinoma (ESCC), pancreatic cancer, colorectal cancer (CRC), bladder cancer (BC), and cervical cancer (CC).
NORAD, non-coding RNA activated by DNA damage, has a critical role in maintaining genomic stability. NORAD maintains both ploidy and chromosomal stability by sequestering PUMILIO proteins, which repress key mitotic, DNA repair, and DNA replication factors to repress the stability and translation of mRNAs to which they bind. NORAD is unusually abundant with expression in the range of ~500–1000 copies per cell in human cell lines, and the presence of at least 15 PUMLIIO response elements (PREs) per NORAD transcript further amplifies, by more than an order of magnitude, the number of competitive binding sites provided by this lncRNA, this strongly support its function as a bona fide molecular decoy. Also, multiple lines of evidence indicate that NORAD affects genomic stability through its direct interaction with Pumilio2 (PUM2) and possibly Pumilio 1 (PUM1),which are known to bind to the 3′UTR of target mRNAs via an 8-nt specific sequence and reduce their stability. In addition, NORAD is essential for the assembly of the ribonucleoprotein complex NARC1 and NORAD assembles a topoisomerase complex critical for genome stability.
NORAD is an oncogenic lncRNA. Increased NORAD expression might serve as a novel molecular predictor of poor prognosis in ESCC patients and maybe a potential target for diagnosis and gene therapy, and high NORAD expression could serve as an independent prognostic factor for overall survival of patients with transitional BC.
It is found that NORAD functions as a ceRNA through competition for miR-125a-3p to play the oncogenic role in the pathogenesis of pancreatic cancer, inhibition of miR-202-5p to promote colorectal cancer progression, modulating miR-590-3p/SIP1 axis in colorectal cancer.
Also, NORAD upregulates transforming growth factor-β (TGF-β) signaling and regulates TGF-β-induced epithelial-to-mesenchymal transition (EMT)-like phenotype, which is a critical step in the progression of lung adenocarcinoma, A549 cells.
- bladder cancer
- breast cancer
- cervical cancer
- colorectal cancer
- esophageal squamous cell carcinoma
- pancreatic cancer
>gi|226246632|ref|NR_027451.1| Homo sapiens non-coding RNA activated by DNA damage (NORAD), long non-coding RNA
Labs working on this lncRNA
- Department of Molecular Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9148, USA.
- Pathobiology Graduate Program, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
- Cancer Institute, University of Mississippi Medical Center, Jackson, MS, USA.
- Department of Oncology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, China.
- Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, USA.
- State Key Laboratory of Oncology in South China & Collaborative Innovation Center for Cancer Medicine,Sun Yat-sen University Cancer Center, Guangzhou, China.
- Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang, China.
- Research Institute of Pancreatic Disease, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
- Pancreatic Disease Centre, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
- The First Department of General Surgery, Linyi Central Hospital, No. 17 Yishui County, Linyi 276400, Shandong Province, China.
- The First Department of Endocrinology, Linyi Central Hospital, No. 17 Yishui County, Linyi 276400, Shandong Province, China.
- Department of Urology, Xiangya Hospital, Central South University, Changsha, Hunan Province, PR China.
- Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
- Department of Respiratory Medicine and Infectious Diseases, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
- Department of Obstetrics and Gynecology, Huaihe Hospital of Henan University, Kaifeng 475000, Henan Province, China.
- Department of Surgery, Kaifeng University, Kaifeng 475000, Henan Province, China.
- Department of Biological Regulation, Weizmann Institute of Science, Rehovot 76100, Israel.
- Department of Molecular Genetics, Weizmann Institute of Science, Rehovot 76100, Israel.
- Broad Institute of MIT and Harvard, Cambridge, MA, USA.
- Division of Hematology/Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
- Lee S, Kopp F, Chang TC, Sataluri A, Chen B, Sivakumar S, et al. Noncoding RNA NORAD Regulates Genomic Stability by Sequestering PUMILIO Proteins. Cell. 2016;164(1-2):69-80.
- Munschauer M, Nguyen CT, Sirokman K, Hartigan CR, Hogstrom L, Engreitz JM, et al. The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature. 2018.
- Tichon A, Gil N, Lubelsky Y, Havkin Solomon T, Lemze D, Itzkovitz S, et al. A conserved abundant cytoplasmic long noncoding RNA modulates repression by Pumilio proteins in human cells. Nature communications. 2016;7:12209.
- Huo H, Tian J, Wang R, Li Y, Qu C, Wang N. Long non-coding RNA NORAD upregulate SIP1 expression to promote cell proliferation and invasion in cervical cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie. 2018;106:1454-60.
- Liu H, Li J, Koirala P, Ding X, Chen B, Wang Y, et al. Long non-coding RNAs as prognostic markers in human breast cancer. Oncotarget. 2016;7(15):20584-96.
- Wu X, Lim ZF, Li Z, Gu L, Ma W, Zhou Q, et al. NORAD Expression Is Associated with Adverse Prognosis in Esophageal Squamous Cell Carcinoma. Oncology research and treatment. 2017;40(6):370-4.
- Li H, Wang X, Wen C, Huo Z, Wang W, Zhan Q, et al. Long noncoding RNA NORAD, a novel competing endogenous RNA, enhances the hypoxia-induced epithelial-mesenchymal transition to promote metastasis in pancreatic cancer. Molecular cancer. 2017;16(1):169.
- Zhang J, Li XY, Hu P, Ding YS. LncRNA NORAD contributes to colorectal cancer progression by inhibition of miR-202-5p. Oncology research. 2018.
- Li Q, Li C, Chen J, Liu P, Cui Y, Zhou X, et al. High expression of long noncoding RNA NORAD indicates a poor prognosis and promotes clinical progression and metastasis in bladder cancer. Urologic oncology. 2018;36(6):310 e15- e22.
- Ventura A. NORAD: Defender of the Genome. Trends in genetics : TIG. 2016;32(7):390-2.
- Kawasaki N, Miwa T, Hokari S, Sakurai T, Ohmori K, Miyauchi K, et al. Long noncoding RNA NORAD regulates transforming growth factor-beta signaling and epithelial-to-mesenchymal transition-like phenotype. Cancer science. 2018;109(7):2211-20.