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Small RNA sequencing of sessile serrated polyps identifies microRNA profile associated with colon cancer

Priyanka Kanth1,2, Mark W Hazel1, Kenneth M Boucher2,3

  • 1Division of Gastroenterology, Department of Internal Medicine, University of Utah, Salt Lake City, Utah.

Genes, Chromosomes & Cancer
|September 29, 2018
PubMed

Insights

Sessile serrated adenoma/polyps (SSA/Ps) are linked to colon cancer. MicroRNAs (miRNAs) show distinct expression patterns in SSA/Ps, potentially influencing cancer development and targeting growth pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Sessile serrated adenoma/polyps (SSA/Ps) represent a significant precursor to colon cancer, accounting for 20-30% of cases.
  • Small non-coding RNAs, specifically microRNAs (miRNAs), are implicated in oncogenesis and tumor suppression.
  • Understanding miRNA dysregulation in SSA/Ps is crucial for elucidating serrated pathway tumorigenesis.

Purpose of the Study:

  • To characterize the microRNA (miRNA) expression profiles in sessile serrated adenoma/polyps (SSA/Ps).
  • To compare miRNA profiles of SSA/Ps with hyperplastic polyps (HPs), adenomatous polyps, and normal colon tissue.
  • To investigate the relationship between SSA/P-specific miRNAs and colon cancer molecular subtypes.

Main Methods:

  • Small RNA sequencing (RNA-seq) was performed on 108 samples, including SSA/Ps, HPs, adenomatous polyps, and paired normal colon tissue.
  • RNA-seq data from SSA/Ps were compared with data from 212 colon cancers from The Cancer Genome Atlas (TCGA).
  • Differential miRNA expression was validated using RT-qPCR for specific miRNAs (MIR31-5p, MIR135B-5p, MIR378A-5p).

Main Results:

  • Twenty-three miRNAs were differentially expressed in SSA/Ps compared to normal colon tissue, and six were differentially expressed compared to HPs.
  • SSA/P-specific miRNAs exhibited similar expression patterns in colon cancers with genomic aberrations characteristic of serrated cancers.
  • Correlation analysis indicated that multiple consensus molecular subtypes are associated with the serrated neoplasia pathway.

Conclusions:

  • Distinct miRNA expression signatures are associated with sessile serrated adenoma/polyps (SSA/Ps).
  • These SSA/P-specific miRNAs may play a role in the development of serrated pathway colon cancers.
  • Pathway analysis suggests that dysregulated miRNAs in SSA/Ps frequently target growth factor signaling pathways.
Keywords:
RNA sequencingcolon cancergene expressionhyperplastic polypsmicroRNAssessile serrated adenoma/polyps

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