B0091 - Examination of Downregulated miRNAs and Associated Pathways in Colorectal Cancer: A Systematic Review

Monday, October 24, 2022

10:00 AM – 12:00 PM ET

Location: Crown Ballroom

Has Audio

Presenting Author(s)

Ahamed Khalyfa, DO

Franciscan Health
Olympia Fields, Illinois

Ahamed Khalyfa, DO¹, Navkiran Randhawa, DO¹, Abdelnaby Khalyfa, PhD²
¹Franciscan Health, Olympia Fields, IL; ²University of Missouri, Columbia, IL

Introduction: Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Many biological molecules play a significant role in the pathogenesis of CRC including miRNAs, small RNA molecules that regulate the translation and stability of specific target mRNAs. Given the involvement of miRNAs on all fronts of CRC including pathogenesis, diagnosis, prognosis and potential therapy, it is imperative to fully understand their role within this deadly disease. With this study, we examined unique miRNAs which were upregulated in patients with CRC.

Methods: We searched PubMed and the Cochrane Database of Systematic Reviews (CDSR) through Wiley from 2016 to 2022 for keywords “miRNA”,” micro-RNA”, “colon cancer”, “colorectal cancer”, “CRC”. From this data, we performed computational analysis using MicroInspector, miRanda, PicTar, RNA22, DIANA, softwares and identified unique upregulated miRNAs. We further examined the list of the biological pathways identified from predicted target genes of downregulated miRNAs and selected the top 4 pathways of clinical significance. We then filtered common miRNAs between these selected pathways and identified unique miRNAs between the top 4 pathways.

Results: Through our computational analysis, we identified 59 upregulated miRNAs from studies of patients with CRC. We then identified a list of the biological pathways identified from downregulated miRNAs target genes. We also highlighted the relevant pathways which are associated with cancer including: MAPK signaling pathway (p -value 2.79 E-08), ErbB signaling (p-value 6.69E-08), PI3K-Akt (p-value 2.87E-06). We further investigated the highlighted pathways and found unique miRNAs associated with these pathways. Namely, hsa-mir-296-3p and hsa-mir-198-3p were identified, suggesting that these miRNAs may play an important role in those pathways.

Discussion: MicroRNAs play an important role in CRC initiation, progression, and development through manipulation of cell stemness, angiogenesis, apoptosis, and the epithelial–mesenchymal transition (EMT) of tumor cells. With this study we identified unique clinically relevant metabolic pathways of CRC affected by downregulated miRNAs. We also identified the unique miRNAs hsa-mir-296b-3p and hsa-mir-198-3p. Further work is necessary to identify specific roles of these miRNA candidates as biological markers or therapeutic targets for patients with CRC.

Pathway	p-value	#genes	#miRNAs
ECM-receptor interaction	4.97E-32	58	23
Proteoglycans in cancer	6.89E-12	124	26
Focal adhesion	5.81E-09	137	27
MAPK signaling pathway	2.79E-08	158	26
ErbB signaling pathway	6.69E-08	60	25
Renal cell carcinoma	4.80E-07	49	25
Axon guidance	1.08E-06	83	27
Regulation of actin cytoskeleton	2.17E-06	129	27
PI3K-Akt signaling pathway	2.87E-06	197	28
Rap1 signaling pathway	3.71E-06	127	26

Table: List of the biological pathways identified from predicted target genes of downregulated miRNAs

Disclosures:

Ahamed Khalyfa indicated no relevant financial relationships.

Navkiran Randhawa indicated no relevant financial relationships.

Abdelnaby Khalyfa indicated no relevant financial relationships.

Ahamed Khalyfa, DO¹, Navkiran Randhawa, DO¹, Abdelnaby Khalyfa, PhD². B0091 - Examination of Downregulated miRNAs and Associated Pathways in Colorectal Cancer: A Systematic Review, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.