Mutations in untranslated non-coding regions of EGFR, AKT1 & HRAS modulate their expression regulatory networks to facilitate progression of colorectal cancer.

Authors

Iqra Abdullah, Samina Ejaz

Published in

Functional & integrative genomics. Volume 26. Issue 1. Sep 23, 2026. Epub Sep 23, 2026.

Abstract

Mutations in the untranslated region (UTR) of a gene dysregulate its expression by disrupting the regulatory elements. Defective EGFR, AKT1, and HRAS are known to promote colorectal cancer (CRC) by activating oncogenic signaling pathways. The current study aimed to screen the Pakistani CRC patients for UTR mutations of EGFR, AKT1, and HRAS genes and investigate the functional impact of detected mutations on regulatory elements. The genomes of CRC patients were analyzed by whole-exome sequencing. All the identified UTR mutations were subjected to extensive in silico analysis to study the functional consequences on pathogenicity, oncogenicity, regulatory elements, mRNA structure, transcription factor binding sites, and miRNA binding sites. Moreover, miRNA expression, pathway, protein-protein interaction and gene enrichment analysis were also performed. The present study identified UTR mutations of EGFR (n = 5), AKT1 (n = 6), and HRAS (n = 3) in Pakistani CRC patients. Among 5' UTR mutations of EGFR, c.-216G > T causes loss of TF and motif sequences, c.-191 A > C increases strength of the motif sequences, AKT1: c.-463dupG, c.-47 C > T, and c.-478G > C, and HRAS: c.-101 C > T mutations stabilize the mRNA structure and alter the motif sequence and transcription factor binding sites. Whereas 3' UTR mutations of EGFR c.*281dupA and c.*774T > C and AKT1 c.*301C > T cause loss of oncomiR sites. PPI and pathway enrichment analysis show that EGFR, AKT1, and HRAS interact with other oncogenes. This study reported the presence of damaging mutations in the regulatory region, which may alter the expression of EGFR, AKT1, and HRAS. The information thus generated could facilitate designing personalized therapy.

PMID:
42773328
Bibliographic data and abstract were imported from PubMed on 23 Sep 2026.

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