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...
Main Authors: | , , , , , , |
---|---|
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 |
_version_ | 1818198697541894144 |
---|---|
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. |
first_indexed | 2024-12-12T02:09:59Z |
format | Article |
id | doaj.art-bcddc8500b244b8c98eba693955d12bd |
institution | Directory Open Access Journal |
issn | 1475-2867 |
language | English |
last_indexed | 2024-12-12T02:09:59Z |
publishDate | 2020-07-01 |
publisher | BMC |
record_format | Article |
series | Cancer Cell International |
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 |
work_keys_str_mv | AT jiaxinliu aberrantmethylationandmicrornatargetregulationareassociatedwithdownregulatedneurl1badiagnosticandprognostictargetincoloncancer AT zhaoliu aberrantmethylationandmicrornatargetregulationareassociatedwithdownregulatedneurl1badiagnosticandprognostictargetincoloncancer AT xiaozhizhang aberrantmethylationandmicrornatargetregulationareassociatedwithdownregulatedneurl1badiagnosticandprognostictargetincoloncancer AT yanliyan aberrantmethylationandmicrornatargetregulationareassociatedwithdownregulatedneurl1badiagnosticandprognostictargetincoloncancer AT shuaishao aberrantmethylationandmicrornatargetregulationareassociatedwithdownregulatedneurl1badiagnosticandprognostictargetincoloncancer AT demaoyao aberrantmethylationandmicrornatargetregulationareassociatedwithdownregulatedneurl1badiagnosticandprognostictargetincoloncancer AT tuotuogong aberrantmethylationandmicrornatargetregulationareassociatedwithdownregulatedneurl1badiagnosticandprognostictargetincoloncancer |