Differential Expression of MicroRNAs in the Colorectal Serrated Neoplasia Pathway and Adenoma-Carcinoma Sequence
- Takashi Murakami 1, Hiroyuki Mitomi 2, Naoki Tsugawa 1, Yudai Otsuki 1, Eiji Kamba 1, Yuichiro Kadomatsu 2, Takuo Hayashi 2, Tsuyoshi Saito 2, Tomoyoshi Shibuya 1,3, Takashi Yao 2, Akihito Nagahara 1,3
- 1Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan.
- 2Department of Human Pathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
- 3Department of Pathophysiological Research and Therapeutics for Gastrointestinal Disease, Juntendo University Faculty of Medicine, Tokyo, Japan.
- 0Department of Gastroenterology, Juntendo University Faculty of Medicine, Tokyo, Japan.
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View abstract on PubMed
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.
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