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The "LINC" between Δ40p53-miRNA Axis in the Regulation of Cellular Homeostasis

Apala Pal1, Pritam Kumar Ghosh1, Saumitra Das1

  • 1Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India.

Molecular and Cellular Biology
|June 7, 2023
PubMed

Insights

Delta40p53 (Δ40p53), a p53 isoform, controls cell growth by regulating LINC00176, a long noncoding RNA. This axis impacts cell proliferation and viability independently of full-length p53.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • The p53 protein family plays a crucial role in cellular homeostasis.
  • Delta40p53 (Δ40p53) is a translationally distinct isoform of p53.
  • Δ40p53 has demonstrated the ability to inhibit cell growth independently of full-length p53 (FL-p53) through microRNA regulation.

Purpose of the Study:

  • To investigate the role of Δ40p53 in regulating the long noncoding RNA (lncRNA)-microRNA (miRNA)-cellular process axis.
  • To specifically elucidate the interaction between Δ40p53 and the lncRNA LINC00176.
  • To understand the downstream consequences of this regulatory axis on cellular functions.

Main Methods:

  • Analysis of LINC00176 expression in response to Δ40p53 modulation (overexpression and knockdown).
  • Investigation of Δ40p53's transcriptional and post-transcriptional regulation of LINC00176.
  • RNA immunoprecipitation assays to identify miRNA targets of LINC00176.
  • Functional assays (proliferation, viability, epithelial marker expression) in HCT116 p53-/- cells with manipulated LINC00176 levels.

Main Results:

  • LINC00176 levels were significantly affected by Δ40p53 levels, more so than by FL-p53 levels.
  • Δ40p53 was found to transcriptionally activate LINC00176 and influence its stability.
  • LINC00176 was shown to sequester miRNAs, thereby modulating mRNA targets involved in cellular processes.
  • Manipulation of LINC00176 in Δ40p53-expressing cells impacted cell proliferation, viability, and epithelial marker expression.

Conclusions:

  • Δ40p53 plays a critical role in regulating the LINC00176 lncRNA-miRNA-mRNA axis.
  • This regulatory pathway operates independently of FL-p53.
  • The Δ40p53-LINC00176 axis is important for maintaining cellular homeostasis, affecting proliferation and cell fate.
Keywords:
Effect on cellular processesLINC00176 regulationlncRNA-miRNA axisp53 isoformΔ40p53 function

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