GUARDIN

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GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability.

Annotated Information

Name

GUARDIN

Alias

LINC01759: long intergenic non-protein coding RNA 1759

Characteristics

GUARDIN is located between the genes miR-34a and hexose-6-phosphate dehydrogenase/glucose 1-dehydrogenase (H6PD) [1]. GUARDIN and the miR-34a host gene MIR34AHG overlap and share the same promoter.[1]

Expression

GUARDIN expression positively correlates with the expression of miR-34a and MIR34AHG, but neither silencing nor overexpression of GUARDIN altered the expression of miR-34a, its target Snail as well as MIR34AHG [1]. GUARDIN expression is regulated by p53 [1]. GUARDIN is expressed at higher levels in colon cancers with wild-type p53 than in those carrying mutant p53 [1].

Regulation

GUARDIN expression is primarily regulated by wild-type p53; when p53 is induced, GUARDIN appeares markedly abundant [1].

Function

GUARDIN is important for maintaining genomic integrity under steady-state conditions and after exposure to exogenous genotoxic stress [1]. GUARDIN contains eight regions complementary to the ‘seed’ region of miR-23a, and sequesters microRNA-23a to maintain the expression of telomeric repeat-binding factor 2 (TRF2), preventing chromosome end-to-end fusion [1].

In addition, GUARDIN sustains breast cancer 1 (BRCA1) stability by acting as an RNA scaffold to facilitate the heterodimerization of BRCA1 and BRCA1-associated RING domain protein 1 (BARD1) [1]. GUARDIN knockdown increases the polyubiquitination of BRCA1 [1]. As such, GUARDIN silencing triggers apoptosis and senescence, enhances cytotoxicity of additional genotoxic stress and inhibits cancer xenograft growth [1]. Thus, GUARDIN may constitute a target for cancer treatment.

Diseases

  • Breast cancer [1]
  • Colon cancer [1]

Labs working on this lncRNA

  • Chinese Academy of Sciences (CAS) Key Laboratory of Innate Immunity and Chronic Disease, CAS Centre for Excellence in Cell and Molecular Biology, Innovation Centre for Cell Signalling Network, School of Life Sciences, University of Science and Technology of China, Hefei, China. [1]

References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1: Hu WL, Jin L, Xu A, Wang YF, Thorne RF, Zhang XD, Wu M. GUARDIN is a p53-responsive long non-coding RNA that is essential for genomic stability. NatCell Biol. 2018 Apr;20(4):492-502. doi: 10.1038/s41556-018-0066-7. Epub 2018 Mar 28. PubMed PMID: 29593331.

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