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Altered miR-21, miRNA-148a Expression in Relation to KRAS Mutation Status as Indicator of Adenoma-Carcinoma Transitional Pattern in Colorectal Adenoma and Carcinoma Lesions

  • Somayeh Igder
  • Javad Mohammadiasl
  • Pooneh MokarramEmail author
Original Article
  • 10 Downloads

Abstract

Sporadic colorectal cancer (CRC) is a fatal disease, mostly known as the silent killer, due to the fact that this disease is asymptomatic before diagnosis in advanced stage. Screening and the early detection of CRC and colorectal adenoma (CRA) by non-aggressive molecular biomarkers’ signature is useful for improvement of survival rate in CRC patients. To achieve such a goal, a better understanding of distinct molecular abnormalities as candidate biomarkers in CRC development is crucial. In this study, seventy-five archived FFPE CRC samples, including colorectal adenocarcinoma, adenomatous polyps (adenoma), and adjacent non-neoplastic mucosa were collected for the investigation by Sanger sequencing at the DNA level and by real-time PCR at the RNA level. The results of the KRAS mutational analysis have shown that the majority of somatic mutations in the KRAS affect only one codon, mainly codon 12(p.G12D) with low frequency in adenomas (13.3%) versus CRCs (36%). The results of dysregulated epigenetic changes of miR-21 clearly showed upregulation of expression in colorectal adenocarcinoma, compared to non-neoplastic mucosa, in colorectal adenoma vs non-neoplastic mucosa: (p < 0.001) and in CRC versus adenoma (p < 0.001); while miR-148a expression were significantly downregulated in CRC, compared to non-neoplastic mucosa, in colorectal adenoma vs non-neoplastic mucosa, and in adenoma vs CRC (p < 0.001). Our findings support the important role of miR-21 in stages I–II of CRC, and the KRAS G12D mutant, and differential miR-148a expression, in advanced stages of CRC.

Keywords

Sporadic CRC miR-21 miR-148a The KRAS G12D mutant CRC development 

Notes

Acknowledgements

We thank our colleagues at the Department of Gastrointestinal Surgery and Institute of Digestive Surgery for providing tissue samples and pathological records. We would like to thank all colleagues who performed research in the field of microRNA and colorectal cancer. This study was financially supported by the Shiraz University of Medical Sciences [with Grant Number 94-01-01-10626]

Compliance with Ethical Standards

Conflict of interest

All authors declare that they have no conflict of interest.

Supplementary material

10528_2019_9918_MOESM1_ESM.docx (22 kb)
Supplementary file1 (DOCX 22 kb)
10528_2019_9918_MOESM2_ESM.docx (14 kb)
Supplementary file2 (DOCX 13 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Biochemistry, School of MedicineShiraz University of Medical SciencesShirazIran
  2. 2.Department of Medical Genetics, School of MedicineAhvaz Jundishapur University of Medical SciencesAhvazIran
  3. 3.Colorectal Cancer Research Center and Department of BiochemistryShiraz University of Medical SciencesShirazIran

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