Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer

Abstract

Background Aberrant methylation and miRNA-target-gene regulation function as important mechanisms for gene inactivation in colon carcinogenesis. Although a serious of molecular events (such as aberrant alterations of genomics and epigenetics) have been identified to be related to prognostic in colon cancer (CC) patients, beneficial biomarkers for early diagnosis and prognostic evaluation remain largely unknown. Methods In our study, the role of NEURL1B, including gene expression analysis, methylation characteristic, miRNA-target regulation, diagnostic and prognostic significance, were evaculated using multiple bioinformatic tools based on TCGA database and clinical samples. Results Our data showed that NEURL1B was aberrantly downregulated in CC, regardless of the mRNA level or protein level. Moreover, ROC curve and multivariate Cox regression analysis demonstrated that NEURL1B was a diagnostic and independent prognostic facter for CC patients. Of interest, methylation of NEURL1B was also high and closely associated with poor survival in CC. In addition, multiple NEURL1B-target miRNAs were found to be overexpressed in CC tissues. Thus, our findings suggested that NEURL1B participated in the pathological processes of CC as a tumor suppressor gene. Double management, including DNA methylation modification and miRNA-target regulation, were considered to be related to the downregulation of NEURL1B. Importantly, there existing be an significant intersection between miRNAs-target pathways and NEURL1B-target pathways, suggesting that miR-17 and miR-27a might promote tumor cell malignant property by targeting NEURL1B degradation via the activation of PI3K/AKT signaling pathway. Conclusions Taking together, the first investigation of NEURL1B in CC provide us a strong evidences that it might be served as a potential biomarkers for early diagnosis and prognostic evaluation in CC.

Aberrantly hypermethylated ARID1B is a novel biomarker and potential therapeutic target of colon adenocarcinoma

“…Consistent with the significant downregulation of ARID1B expression in colon cell lines and TCGA tissues, ARID1B was hypermethylated in COAD tissues. Comparison of these findings with those of previous studies confirmed silenced expression of genes, especially ARID1B by aberrant methylation of DNA in cancer (Chuang and Jones, 2007;Khursheed et al, 2013;Liu et al, 2020;Tan et al, 2020). AKR1C2 mRNA, a gene previously identified as a Nrf2-target, was not found in HCT116 cells (Ebert et al, 2011).…”

Immune depletion of the methylated phenotype of colon cancer is closely related to resistance to immune checkpoint inhibitors

“…Herein, using transcriptome, DNA methylation, and driver mutations of CRC, we developed a classifier based on multi-omics integration for the prognosis prediction of CRC for the first time. At present, many studies have proved that CRC is the result of accumulation of multiple gene mutations and epigenetic modifications, and DNA hypermethylation or hypomethylation can be used as epigenetic biomarkers to predict the occurrence and prognostic effects of CRC (75)(76)(77). Driver mutations in the genome can be viewed as responsible for molecular changes associated with CRC progression, so targeting such genes for the elimination of multiple CRC gene dependencies could significantly improve efficacy (78).…”

Characterizing and Targeting Genes Regulated by Transcription Factor MYBL2 in Lung Adenocarcinoma Cells

“…In addition to CENPA, we identified additional potential target genes of MYBL2 and FOXM1 in lung adenocarcinoma ( Figure 4 ). For example, neuralized E3 ubiquitin protein ligase 1B (NEURL1B) is known to act as a tumor suppressor gene in colon cancer and medulloblastoma [ 41 , 42 ]. However, in our study, we found that NEURL1B acts more like an oncogene in lung adenocarcinoma cells.…”