WT1-AS/IGF2BP2 Axis Is a Potential Diagnostic and Prognostic Biomarker for Lung Adenocarcinoma According to ceRNA Network Comprehensive Analysis Combined with Experiments

Cells. 2021 Dec 23;11(1):25. doi: 10.3390/cells11010025.

Abstract

Lung adenocarcinoma (LUAD) is one of the most common malignancies, and there is still a lack of effective biomarkers for early detection and prognostic prediction. Here, we comprehensively analyze the characteristics of. an RNA sequencing data set of LUAD samples. In total, 395 long non-coding RNAs (lncRNAs), 89 microRNAs (miRNAs), and 872 mRNAs associated with c-Myc were identified, which were differentially expressed between tumor and normal tissues. The most relevant pathway was found to be WT1-AS-miR-200a-3p-IGF2BP2 according to the rules of competitive endogenous RNA (ceRNA) regulation. WT1-AS and IGF2BP2 expression were positively correlated and increased in LUAD samples, while miR-200a-3p had relatively low expression. The high expression of WT1-AS and IGF2BP2 was associated with poor prognosis in LUAD patients, while low expression of miR-200a-3p predicted reduced survival (p < 0.05). The analysis of the multi-gene regulation model indicated that the WT1-AS (downregulation)-miR-200a-3p (upregulation)-IGF2BP2 (downregulation) pattern significantly improved the survival of LUAD patients. Finally, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were detected in LUAD cells, and the results are consistent with the bioinformatics analysis. In summary, the WT1-AS/IGF2BP2 axis is a potential prognostic biomarker in LUAD and is expected to become an effective target for diagnosis and treatment.

Keywords: WT1-AS/IGF2BP2 axis; ceRNA network; lung adenocarcinoma; novel biomarkers; prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / genetics*
  • Adenocarcinoma of Lung / pathology
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Line, Tumor
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Gene Ontology
  • Gene Regulatory Networks*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics
  • MicroRNAs / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-myc / metabolism
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Reproducibility of Results

Substances

  • Biomarkers, Tumor
  • IGF2BP2 protein, human
  • MIRN200 microRNA, human
  • MicroRNAs
  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • RNA-Binding Proteins
  • WT1-as long non-coding RNA, human