长链非编码 RNA EGFR-AS1 在结直肠癌中的作用：通过 miRNA-133b 海绵和 EGFR/STAT3 轴调控在肿瘤发生和生存中的潜在作用。

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

机构信息

Medical Biochemistry Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

Pathology Department, Faculty of Medicine, Tanta University, Tanta, Egypt.

出版信息

Br J Biomed Sci. 2021 Jul;78(3):122-129. doi: 10.1080/09674845.2020.1853913. Epub 2021 Apr 14.

DOI:10.1080/09674845.2020.1853913

PMID:33211633

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.

摘要

背景

结直肠癌是全球最常见的癌症之一，也是癌症相关死亡的主要原因。因此，已经提出了用于结直肠癌的分子生物标志物。长链非编码 RNA EGFR-AS1 在结直肠癌中的作用尚不清楚。我们旨在评估其在结直肠癌不同阶段的表达，并确定其在调节 miR-133b/EGFR/STAT3 信号通路中的任何可能作用。

材料和方法

通过定量实时 RT-转录 PCR 评估 130 例结直肠癌样本和 30 例正常组织中 EGFR-AS1 和 miR-133b 的相对表达。使用免疫组织化学评估 EGFR 表达。此外，通过 ELISA 测定 p-EGFR、p-STAT3 和凋亡蛋白的水平。

结果

EGFR-AS1 和 EGFR 的过表达均与结直肠癌状态（均 P < 0.01）、分级（均 P < 0.01）和转移（P < 0.01 和 P = 0.019）呈正相关。EGFR-AS1 和 miR-133b 呈显著负相关（P < 0.01）。miR-133b 低表达与 EGFR 过表达和 p-STAT3 水平升高呈负相关。EGFR-AS1 是结直肠癌患者生存的独立预后因素（P < 0.01，HR 2.06；95%CI 1.32-3.19），其中 EGFR-AS1 低表达与生存率提高相关（P = 0.003）。