Investigating the Association between LncRNA NR2F2-AS1, miR-320b, and BMI1 in Gastric Cancer: Insights into Expression Profiles as Potential Biomarkers for Disease Management

Microrna. 2024;13(3):211-224. doi: 10.2174/0122115366291818240606112725.

Abstract

Aim: This study aims to investigate the potential role of lncRNA NR2F2-AS1 in the development of gastric cancer by affecting the levels of miR-320b and BMI1.

Background: Gastric cancer is a high-mortality malignancy, and understanding the underlying molecular mechanisms is crucial. Non-coding RNAs play an important role in gene expression, and their dysregulation can lead to tumor initiation and progression.

Objective: This study aims to determine the pathological role of LncRNA NR2F2-AS1 in gastric cancer progression and its association with the clinicopathological characteristics of patients.

Methods: Bioinformatics databases were used to predict the expression levels and interactions between the studied factors to achieve this objective. The expression pattern of NR2F2-AS1/miR- 320b/BMI1 in 40 pairs of tumor and adjacent normal tissues was examined using RT-PCR, IHC, and western blot. The correlation, ROC curve, and survival analyses were also conducted for the aforementioned factors.

Results: The results showed an increase of more than 2-fold for BMI-1 and lncRNA NR2F2-AS1 in lower stages, and the elevation continued with the increasing stage of the disease. This correlated with significant downregulation of miR-320b and PTEN, indicating their association with gastric cancer progression and decreased patient survival. LncRNA NR2F2-AS1 acts as an oncogene by influencing the level of miR-320b, altering the amount of BMI1. A reduction in the amount of miR-320b against lncRNA NR2F2-AS1 and BMI1 directly correlates with a reduced overall survival rate of patients, especially if this disproportion is more than 3.0. ROC curve analysis indicated that alteration in the lncRNA NR2F2-AS1 level showed more than 98.0% sensitivity and specificity to differentiate the lower from higher stages of GC and predict the early onset of metastasis.

Conclusion: In conclusion, these results suggest that NR2F2-AS1/miR-320b/BMI1 has the potential to be a prognostic as well as diagnostic biomarker for gastric cancer.

Keywords: BMI1; LncRNA NR2F2-AS1; MiR-320b; biomarker.; expression; gastric cancer.

MeSH terms

  • Aged
  • Biomarkers, Tumor* / genetics
  • COUP Transcription Factor II / genetics
  • Female
  • Gene Expression Regulation, Neoplastic* / genetics
  • Humans
  • Male
  • MicroRNAs* / genetics
  • Middle Aged
  • Polycomb Repressive Complex 1* / genetics
  • Prognosis
  • RNA, Long Noncoding* / genetics
  • Stomach Neoplasms* / diagnosis
  • Stomach Neoplasms* / genetics
  • Stomach Neoplasms* / pathology

Substances

  • MIRN320 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Biomarkers, Tumor
  • Polycomb Repressive Complex 1
  • BMI1 protein, human
  • COUP Transcription Factor II
  • NR2F2 protein, human