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Polymorphism Pro64His within galectin-3 has functional consequences at proteome level in thyroid cells.

Roberto Silvestri1, Lorenzo Zallocco2, Alda Corrado1

  • 1Department of Biology, Genetic Unit, University of Pisa, Pisa, Italy.

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|June 27, 2024
PubMed
Summary
This summary is machine-generated.

The rs4644 single nucleotide polymorphism (SNP) in galectin-3 (gal-3) influences protein structure and expression, impacting cancer risk. This SNP affects gal-3

Keywords:
CRISPR/Cas9differentiated thyroid carcinoma (DTC)functional polymorphism rs4644galectin-3 (gal3)papillary thyroid carcinoma (PTC)proteome

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Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • The galectin-3 (gal-3) gene (LGALS3) rs4644 single nucleotide polymorphism (SNP) influences gal-3 protein function.
  • This SNP has been linked to an increased risk of differentiated thyroid carcinoma (DTC) and other cancers.
  • Understanding the rs4644 SNP's biological impact is crucial for disease risk assessment.

Purpose of the Study:

  • To investigate the functional consequences of the rs4644 SNP on gal-3 protein structure and expression.
  • To analyze the proteomic and transcriptomic changes induced by the rs4644 SNP in thyroid cells.
  • To elucidate the mechanisms by which rs4644 influences gal-3's role in cellular processes.

Main Methods:

  • Utilized CRISPR-Cas9 to create isogenic Nthy-Ori cell lines (NC-P64 and NA-H64) differing only in the rs4644 genotype.
  • Performed comprehensive proteomic analysis to identify differentially expressed proteins between the cell lines.
  • Integrated proteomic data with transcriptomic analysis to correlate protein expression with mRNA levels.

Main Results:

  • Confirmed distinct gal-3 dimerization patterns for H64 (monomer, homodimer, heterodimer) versus P64 (monomer, uncleaved homodimer) variants.
  • Identified significant protein expression alterations, predominantly upregulated in NA-H64 cells, linked to rs4644.
  • Observed that rs4644 influences both mRNA expression and post-transcriptional regulation, affecting gal-3's co-regulatory functions.

Conclusions:

  • The rs4644 SNP modulates gal-3 function through altered dimerization and gene expression regulation.
  • These rs4644-dependent mechanisms contribute to differential disease susceptibility.
  • Findings support the role of gal-3 genetic variants in disease risk stratification.