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

Mingxi Jia,Zheng Li,Yi Shi,Jing Deng,Da Fu,Jie Bai,Yang Xie,Yushui Ma,Zavuga Zuberi,Juan Li,Wen Li

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.

Highlights

Lung cancer is a malignant tumor with the highest morbidity and mortality in the world, and it is a serious threat to human health [1,2]
The long non-coding RNAs (lncRNAs) (WT1-AS)–miRNA–mRNA (IGF2BP2) regulatory axis associated with Lung adenocarcinoma (LUAD) prognosis was identified based on the survival-related analysis and Curiously, we discovered that miR-200a-3p expression was significantly higher in LUAD tissues than in paired non-tumor tissues, contrary to other assays and analyses, and we consider that this may be related to the smaller paired sample size (n = 46)
Our findings demonstrated that high expression of IGF2BP2 was related to poor prognosis in LUAD, and the expression of IGF2BP2 was positively correlated with the TNM stage and tumor size

Summary

Introduction

Lung cancer is a malignant tumor with the highest morbidity and mortality in the world, and it is a serious threat to human health [1,2]. Long non-coding RNA (lncRNA) and microRNA (miRNA) are the most studied noncoding RNAs, and they play an important role in tumor diagnosis and treatment. LncRNAs play an important role in regulating gene expression by binding to chromatin regulatory proteins, and they can interact with other RNAs and proteins to alter chromatin modification and transcriptional or post-transcriptional gene regulation [7,8,9]. BBOX1-AS1 upregulates the expression of SH2B1 by sponging miR-361-3p, thereby promoting the development of colorectal cancer [18]. The role of the lncRNA-related ceRNA regulatory network in LUAD remains unclear, and the establishment of a ceRNA network is very important for the prognosis prediction and treatment decision-making of LUAD patients [19,20]

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