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...

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Main Authors: Jiaxin Liu, Zhao Liu, Xiaozhi Zhang, Yanli Yan, Shuai Shao, Demao Yao, Tuotuo Gong
Format: Article
Language:English
Published: BMC 2020-07-01
Series:Cancer Cell International
Subjects:
Online Access:http://link.springer.com/article/10.1186/s12935-020-01379-5
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author Jiaxin Liu
Zhao Liu
Xiaozhi Zhang
Yanli Yan
Shuai Shao
Demao Yao
Tuotuo Gong
author_facet Jiaxin Liu
Zhao Liu
Xiaozhi Zhang
Yanli Yan
Shuai Shao
Demao Yao
Tuotuo Gong
author_sort Jiaxin Liu
collection DOAJ
description 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.
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spelling doaj.art-bcddc8500b244b8c98eba693955d12bd2022-12-22T00:41:55ZengBMCCancer Cell International1475-28672020-07-0120111310.1186/s12935-020-01379-5Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancerJiaxin Liu0Zhao Liu1Xiaozhi Zhang2Yanli Yan3Shuai Shao4Demao Yao5Tuotuo Gong6Department of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Oncology Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Geriatric Surgery, The First Affiliated Hospital of Xi’an Jiaotong UniversityDepartment of Radiotherapy, The First Affiliated Hospital of Xi’an Jiaotong UniversityAbstract 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.http://link.springer.com/article/10.1186/s12935-020-01379-5Colon cancerMethylationBioinformatic analysisEarly diagnosis and prognosismicroRNA
spellingShingle Jiaxin Liu
Zhao Liu
Xiaozhi Zhang
Yanli Yan
Shuai Shao
Demao Yao
Tuotuo Gong
Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer
Cancer Cell International
Colon cancer
Methylation
Bioinformatic analysis
Early diagnosis and prognosis
microRNA
title Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer
title_full Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer
title_fullStr Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer
title_full_unstemmed Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer
title_short Aberrant methylation and microRNA-target regulation are associated with downregulated NEURL1B: a diagnostic and prognostic target in colon cancer
title_sort aberrant methylation and microrna target regulation are associated with downregulated neurl1b a diagnostic and prognostic target in colon cancer
topic Colon cancer
Methylation
Bioinformatic analysis
Early diagnosis and prognosis
microRNA
url http://link.springer.com/article/10.1186/s12935-020-01379-5
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