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Related Concept Videos

lncRNA - Long Non-coding RNAs02:39

lncRNA - Long Non-coding RNAs

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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Blocking Lymph Flow by Suturing Afferent Lymphatic Vessels in Mice
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lncRNA LINC-PINT controls lymphatic function and inflammatory profile in lymphedema.

Nathalie Laugero1, Claire Peghaire1, Léna Verdu1

  • 1I2MC, Université de Toulouse, Inserm UMR 1297, Toulouse, France.

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Long intergenic non-protein coding RNA (LINC-PINT) is crucial for lymphedema development. Its deficiency in lymphatic endothelial cells reduces lymphedema severity and inflammation in mice.

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Area of Science:

  • Molecular Biology
  • Genetics
  • Immunology

Background:

  • Lymphedema is a chronic condition resulting from lymphatic system dysfunction.
  • Secondary lymphedema, often caused by cancer treatments, significantly impacts patient quality of life.
  • Noncoding RNAs play critical roles in cellular processes, but their specific involvement in lymphedema is not fully understood.

Purpose of the Study:

  • To investigate the role of noncoding RNAs in breast cancer-induced secondary lymphedema.
  • To identify specific long noncoding RNAs (lncRNAs) involved in lymphedema pathogenesis.
  • To elucidate the molecular mechanisms by which identified lncRNAs regulate lymphatic function.

Main Methods:

  • Noncoding RNA profiling of human lymphedema samples.
  • Knockdown of LINC-PINT in lymphatic endothelial cells (LECs).
  • ATAC-seq to assess chromatin accessibility.
  • Conditional deletion of LINC-PINT in mouse lymphatic endothelium (Lnc-Pintlecko).

Main Results:

  • LINC-PINT was identified as the most expressed lncRNA in stressed human LECs and is essential for lymphedema development.
  • LINC-PINT knockdown in LECs increased inflammation-related gene expression.
  • LINC-PINT enhances chromatin accessibility, promoting transcription of genes involved in lymphangiogenesis and immune cell adhesion.
  • LINC-PINT deficiency impaired LEC proliferation, migration, and sprouting.
  • Lnc-Pintlecko mice showed reduced lymphedema, dermal backflow, fibrosis, and inflammation.

Conclusions:

  • LINC-PINT plays a critical role in lymphatic endothelial cell function and lymphedema pathogenesis.
  • LINC-PINT regulates lymphangiogenesis and immune responses through chromatin remodeling.
  • LINC-PINT represents a potential therapeutic target and a valuable biomarker for lymphedema.