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lncRNA LINC00960 promotes apoptosis by sponging ubiquitin ligase Nrdp1-targeting miR-183-5p

Hao Yang1,2, Tianxia Jiang2, Libin Fan1

  • 1College of Life Sciences, Anhui Medical University, Hefei 230032, China.

Acta Biochimica Et Biophysica Sinica
|February 1, 2023
PubMed

Insights

The long noncoding RNA LINC00960 promotes apoptosis by inhibiting miR-183-5p, which normally downregulates Nrdp1. This pathway impacts cancer and neurodegenerative diseases.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Cell Death Research

Background:

  • The ubiquitin ligase Nrdp1/RNF41 targets substrates like BRUCE/BIRC6, regulating apoptosis and autophagy.
  • MicroRNA miR-183-5p is implicated in malignancies and targets numerous genes, including Nrdp1 mRNA.
  • Long noncoding RNA LINC00960's role in regulating gene expression and apoptosis is under investigation.

Purpose of the Study:

  • To investigate the regulatory relationship between LINC00960, miR-183-5p, and Nrdp1 in the context of apoptosis.
  • To determine the functional impact of this regulatory axis on apoptosis and its potential relevance in diseases like cancer.

Main Methods:

  • Quantitative PCR to analyze gene expression levels of LINC00960, miR-183-5p, and Nrdp1 in tumor cell lines.
  • Luciferase reporter assays to confirm the binding of miR-183-5p to the 3'UTR of Nrdp1 mRNA.
  • Overexpression and knockdown experiments to assess the functional effects of LINC00960 and miR-183-5p on Nrdp1 levels and apoptosis.

Main Results:

  • miR-183-5p directly targets Nrdp1 mRNA, downregulating its expression and inhibiting apoptosis.
  • LINC00960 binds to miR-183-5p, inhibiting its activity and consequently upregulating Nrdp1 and promoting apoptosis.
  • Expression levels of LINC00960 positively correlate with Nrdp1 and inversely with miR-183-5p in human tumor samples.

Conclusions:

  • LINC00960 acts as a tumor suppressor by upregulating Nrdp1 and promoting apoptosis via inhibition of miR-183-5p.
  • This LINC00960/miR-183-5p/Nrdp1 axis represents a novel regulatory mechanism in apoptosis.
  • Findings suggest potential therapeutic strategies for apoptosis-related diseases, including cancers and neurodegenerative disorders.
Keywords:
BRUCENrdp1apoptosislncRNAmiRNA

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