TP53COR1
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].
Contents
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
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
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
- ↑ 1.0 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.
- ↑ 2.00 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.
- ↑ 3.0 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.
- ↑ 4.0 4.1 Yoon JH, Abdelmohsen K, Srikantan S, et al. LincRNA-p21 suppresses target mRNA translation[J]. Mol Cell, 2012, 47: 648-655.
- ↑ 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.
- ↑ 6.0 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.
- ↑ 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.
- ↑ 8.0 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.
