TP53COR1

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LincRNA-p21, long intergenic noncoding RNA-p21 gene serves as a repressor in p53-dependent transcriptional responses and participates in diverse biological processes, including apoptosis, cell cycle, metabolism and pluripotency [1].

Annotated Information

Name

TP53COR1: Tumor protein p53 pathway corepressor 1 (HGNC nomenclature)

Synonyms: linc-p21, lincRNA-p21, Trp53cor1

Characteristics

LincRNA-p21 is located on human chromosome 6p21.2 (HGNC). It is approximately 15 kb upstream of Cdkn1a gene in mouse [2]. .

Functions

Function of licRNA-p21 in the p53 transcriptional response. p53 activates the transcription of lincRNA-p21 by binding to its promoter. LincRNA-p21 binds to hnRNP-K, and this interaction imparts specificity to genes repressed by p53 induction [2].

LincRNA-p21 is a direct p53 transcriptional target in response to DNA damage, acts to repress genes that are down-regulated as part of the canonical p53 transcriptional response, is necessary for p53 dependent apoptotic responses to DNA damage in our cell-based systems [2].

TP53COR1 gene repression is mediated (at least in part) by lincRNA binding to heterogeneous nuclear ribonucleoprotein K (hnRNP-K) through its 5' end. hnRNP-K associates with the promoters of many genes repressed by lincRNA-p21 in a lincRNA-p21 dependent manner [2].

Ectopic expression of lincRNA-p21 inhibited cell proliferation, arrested cycle progression and modulated cyclin D1, CDK4 and p21 expression in diffuse large B cell lymphoma (DLBCL) cell lines [3].

LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinoma by facilitating apoptosis [1]. lincRNA-p21 knockdown promoted proliferation and colony formation of HepG2, Huh7 and Bel-7042 cells in vitro, while the overexpression of lincRNA-p21 has reverse effects [1].

LincRNA-p21 interacting with CTNNB1 and JUNB mRNAs may result in ribosome 'drop-off' to inhibit translation of these mRNAs[4].

Expression

lincRNA-p21 expression is downregulated in diffuse large B cell lymphoma (DLBCL) patients [3].

lincRNA-p21 is upregulated in response to stress induction [5].

lincRNA-p21 is downregulated in colorectal cancer (CRC) cell lines and CRC tumor tissues [6]. lincRNA-p21 is downregulated in human hepatocellular carcinoma tissue [1]

lincRNA-p21' is high expressed in ES-NSC of adult mouse[7].

Experiment Forward primer Reverse primer
qRT-PCR 5'-GGGTGGCTCACTCTTCTGGC- 3' 5'-TGGCCTTGCCCGGGCTTGTC- 3'[6]
qRT-PCR 5'-GCTCGACGCTAGGATCTGAC-3' 5'--GCTTTCCACGACGGTGAC- 3'[3]

Regulation

LincRNA-p21 is regulated by p53 at transcriptional level [2].

RNA-binding protein HuR associated with lincRNA-p21 to recruit let-7/Ago2 to lincRNA-p21, leading to lower lincRNA-p21 stability[4].

Disease

  • Colorectal cancer (CRC) [6]
  • Diffuse large B cell lymphoma (DLBCL) [3]
  • Prostate cancer [8]

Labs working on this lncRNA

  • Department of Gastrointestinal Medical Oncology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, Heilongjiang 150040.[6]
  • Department of Pathology, Harbin Medical University, Harbin, Heilongjiang 150081, P.R. China.[6]
  • The Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.[2]
  • Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.[2]
  • Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.[2]
  • The Koch Institute for Integrative Cancer Research, Cambridge, MA 02139, USA.[2]
  • Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA 94305, USA.[2]
  • Department of and Genetics, Stanford University School of Medicine, Stanford, CA 94305, USA.[2]
  • Department of Systems Biology, Harvard Medical School, Boston, MA 02114, USA.[2]
  • Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul, Turkey.[8]
  • Department of Urology, School of Medicine, Istanbul Hospital, Başkent University, Istanbul, Turkey.[8]
  • Department of Urology, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.[8]

References

  1. 1.0 1.1 1.2 1.3 Ning Y, Yong F, Haibin Z, Hui S, Nan Z, & Guangshun Y. LincRNA-p21 activates endoplasmic reticulum stress and inhibits hepatocellular carcinoma[J]. Oncotarget. 2015, 6(29):28151.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D et al. A Large Intergenic Noncoding RNA Induced by p53 Mediates Global Gene Repression in the p53 Response[J]. Cell. 2010, 142(3):409-419.
  3. 3.0 3.1 3.2 3.3 Peng W, Wu J, Feng J. LincRNA-p21 predicts favorable clinical outcome and impairs tumorigenesis in diffuse large B cell lymphoma patients treated with R-CHOP chemotherapy[J]. Clinical and experimental medicine. 2017, 17(1):1-8.
  4. 4.0 4.1 Yoon JH, Abdelmohsen K, Srikantan S, et al. LincRNA-p21 suppresses target mRNA translation[J]. Mol Cell, 2012, 47: 648-655.
  5. Özgür E, Mert U, Isin M, Okutan M, Dalay N, Gezer U. Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells[J]. Clinical and experimental medicine. 2013, 13(2):119-126.
  6. 6.0 6.1 6.2 6.3 6.4 Wang G, Li Z, Zhao Q, Zhu Y, Zhao C, Li X et al. LincRNA-p21 enhances the sensitivity of radiotherapy for human colorectal cancer by targeting the Wnt/β-catenin signaling pathway[J]. Oncology reports. 2014, 31(4):1839-1845.
  7. Sauvageau M, Goff LA, Lodato S, et al. Multiple knockout mouse models reveal lincRNAs are required for life and brain development[J]. Elife, 2013, 2: e01749.
  8. 8.0 8.1 8.2 8.3 Işın M, Uysaler E, Özgür E, Köseoğlu H, Şanlı Ö, Yücel ÖB et al. Exosomal lncRNA-p21 levels may help to distinguish prostate cancer from benign disease[J]. Frontiers in genetics. 2015, 6:168.

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