Differential Expression of MicroRNAs in the Colorectal Serrated Neoplasia Pathway and Adenoma-Carcinoma Sequence

  • 0Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan.

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Summary

This summary is machine-generated.

MicroRNA (miRNA) expression differs between serrated neoplasia pathway and adenoma-carcinoma sequence in colorectal cancer development. The adenoma pathway shows increasing oncogenic miRNAs, while the serrated pathway shows decreasing or stable levels.

Area Of Science

  • Oncology
  • Molecular Biology
  • Genetics

Background

  • Colorectal cancer (CRC) develops via two main pathways: the serrated neoplasia pathway and the adenoma-carcinoma sequence.
  • Sessile serrated lesions (SSLs) and traditional adenomas (ADs) are precursors to these pathways, respectively.
  • MicroRNAs (miRNAs) are key regulators of gene expression implicated in tumorigenesis.

Purpose Of The Study

  • To investigate and compare miRNA expression profiles in precursor lesions and early invasive carcinomas of the serrated and adenoma pathways of colorectal carcinogenesis.
  • To identify specific miRNAs that differentiate these two distinct pathways of CRC development.

Main Methods

  • Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was used to measure miRNA levels.
  • Expression of miR-20a, miR-21, miR-93, and miR-181b was analyzed in 127 colorectal lesions.
  • Lesions included sessile serrated lesions (SSLs), SSLs with high-grade dysplasia (SSL-HD), SSLs with submucosal invasive carcinoma (SSL-SC), traditional adenomas (ADs), ADs with high-grade dysplasia (AD-HD), and ADs with submucosal invasive carcinoma (AD-SC).

Main Results

  • In the serrated pathway, miR-93 and miR-181b levels decreased with progression from SSL to invasive carcinoma.
  • In the adenoma pathway, miR-20a, miR-21, and miR-181b levels increased with progression from AD to invasive carcinoma.
  • Oncogenic miRNA levels (miR-20a, miR-93, miR-181b) were significantly lower in SSL-derived invasive carcinomas compared to AD-derived invasive carcinomas.

Conclusions

  • The serrated neoplasia and adenoma-carcinoma pathways exhibit distinct miRNA expression dynamics during colorectal tumorigenesis.
  • The adenoma pathway is characterized by a progressive increase in oncogenic miRNAs, whereas the serrated pathway shows selective downregulation or plateauing of these miRNAs.
  • Differential miRNA expression likely reflects distinct (epi)genetic alterations underlying these two CRC development routes.