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

Abstract

Sessile serrated adenoma/polyps (SSA/Ps) of the colon account for 20–30% of all colon cancers. Small non-coding RNAs, including microRNAs (miRNAs), may function as oncogenes or tumor suppressor genes involved in cancer development. Small RNA sequencing (RNA-seq) was used to characterize miRNA profiles in SSA/Ps, hyperplastic polyps (HPs), adenomatous polyps and paired uninvolved colon. Our 108 small RNA-seq samples’ results were compared to small RNA-seq data from 212 colon cancers from the Cancer Genome Atlas. Twenty-three and six miRNAs were differentially expressed in SSA/Ps compared to paired uninvolved colon and HPs, respectively. Differential expression of MIR31-5p, MIR135B-5p and MIR378A-5p was confirmed by RT-qPCR. SSA/P-specific miRNAs are similarly expressed in colon cancers containing genomic aberrations described in serrated cancers. Correlation of miRNA expression with consensus molecular subtypes suggests more than one subtype is associated with the serrated neoplasia pathway. Canonical pathway analysis suggests many of these miRNAs target growth factor signaling pathways.

The Molecular Hallmarks of the Serrated Pathway in Colorectal Cancer

“…MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two important classes of RNAs involved in the regulation of gene expression [134]. Their altered expression has been described in CRCs, with distinct profiles observed between the conventional adenoma-carcinoma and serrated-carcinoma progression models [135,136,137]. Even if their role in cancer progression has not been elucidated yet, specific miRNA alterations have also been described in pre-cancerous lesions.…”

“…In a recent study, small RNA sequencing has been performed in 108 colon biopsies with different histology. Differential expression of miRNAs between tumor and healthy mucosal specimens was highlighted, and miRNAs specific of the serrated lesions were identified [136]. In particular, 23 miRNAs appeared differentially expressed between the serrated lesions and their paired healthy colon samples.…”

Colorectal Adenomas—Genetics and Searching for New Molecular Screening Biomarkers

“…Several differentially expressed miRNAs (miR-135b, -378a, -548, -31, and -196b) were observed in SSA/Ps in comparison with HPs. The authors suggested that these miRNAs might serve as a good diagnostic biomarker of serrated polyps [79]. Aslam et al also analyzed miRNAs isolated from FFPE samples and the expression level of miR-135b was progressively increased with the sequential progression of non-affected tissue to adenoma and carcinoma [80].…”

Molecular Features of the Serrated Pathway to Colorectal Cancer: Current Knowledge and Future Directions

“…Also, some of them were identified as potential biomarkers of the serrated pathway development (i.e., miR-335, miR-222, and miR-214). 59 More recently, Kanth et al 60 performed small RNA sequencing in 108 different colon samples to characterize miRNA profiles and found specific miRNAs differentially expressed in serrated lesions compared to normal colon and HPs.…”