Long non-coding RNA EGFR-AS1 in colorectal cancer: potential role in tumorigenesis and survival via miRNA-133b sponge and EGFR/STAT3 axis regulation

Abstract

ABSTRACT Background Colorectal cancer is one of the most common cancers worldwide and a major cause of cancer-related death. Thus molecular biomarkers for colorectal cancer have been proposed. The role of long non-coding RNA EGFR-AS1 in colorectal cancer is still unclear. We aimed to evaluate its expression in different stages of colorectal cancer and determine any possible role in regulating the miR‑133b/EGFR/STAT3 signalling pathway. Materials and Methods The relative expression of EGFR-AS1 and miR‑133b were evaluated by quantitative real-time RT-transcription PCR in 130 colorectal cancer samples and 30 normal tissues. EGFR expression was assessed using immunohistochemistry. Furthermore, levels of p-EGFR, p-STAT3, and apoptotic proteins were determined by ELISA. Results Both EGFR-AS1 and EGFR overexpression were positively linked with colorectal cancer status (both p < 0.01), grade (both p < 0.01), and metastasis (P < 0.01 and p = 0.019 respectively). EGFR-AS1 and miR-133b were significantly inversely correlated (P < 0.01). Low expression of miR-133b was inversely associated with overexpressed EGFR and increased p-STAT3 levels. EGFR-AS1 was an independent prognostic factor for survival of colorectal cancer patients (P < 0.01, HR 2.06; 95% CI 1.32–3.19) where low EGFR-AS1 expression was associated with higher survival rate (p = 0.003). Conclusion EGFR-AS1 may have a role in colorectal cancer by regulation of miR‑133b/EGFR/STAT3 signalling. It may be a potential biomarker for early diagnosis and predicting the survival rate of colorectal cancer.