Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis

Breast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better...

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Main Authors: Fereshteh Ahmadinejad, Seyed Javad Mowla, Mohammad-Amin Honardoost, Mostafa Gholami Arjenaki, Mohammad Moazeni-Bistgani, Soleyman Kheiri, Hossein Teimori
Format: Article
Language:English
Published: SAGE Publishing 2017-08-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317698362
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author Fereshteh Ahmadinejad
Seyed Javad Mowla
Mohammad-Amin Honardoost
Mostafa Gholami Arjenaki
Mohammad Moazeni-Bistgani
Soleyman Kheiri
Hossein Teimori
author_facet Fereshteh Ahmadinejad
Seyed Javad Mowla
Mohammad-Amin Honardoost
Mostafa Gholami Arjenaki
Mohammad Moazeni-Bistgani
Soleyman Kheiri
Hossein Teimori
author_sort Fereshteh Ahmadinejad
collection DOAJ
description Breast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better prognosis of clinical outcomes would be of the great essence. MicroRNAs are highly conserved small non-coding regulatory RNAs involved in post-transcriptional regulating of gene expression during different cellular mechanisms. Accumulating studies suggest that miR-218 plays a multifunctional role in various cancer types and different stages. Here, to address prognostic significance of miR-218 in breast cancer, we investigate the expression profile of miR-218 and B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI1 ) gene, as one of the putative targets of miR-218, in 33 paired breast tumors and their adjacent normal tissues with respect to the clinicopathological features of patients using quantitative real-time polymerase chain reaction. The correlation of both miR-218 and BMI1 gene expression with overall survival of breast cancer patients was also examined recruiting OncoLNC data portal. Finally, to better understand biological function of miR-218 in breast cancer, we performed in silico Gene Ontology and signaling pathway enrichment analysis on miR-218 targetome. According to our data, significant elevation of the expression of miR-218 and downregulation of BMI1 were observed in clinical breast cancer specimens compared with normal tissues ( p  < 0.0001). The lower expression of miR-218 was associated with lymph node metastases, higher grades, and poorer prognosis (logrank p  = 0.00988), whereas no significant difference in overall survival was observed between patients with higher and lower expression of BMI1 (logrank p  = 0.254). These findings suggest that miR-218 expression profiling might be clinically applicable as a prognostic biomarker in breast cancer. In addition, our in silico enrichment analyses revealed that the association of miR-218 expression with breast cancer prognosis might be through its involvement in endocytosis and gap junction biological pathways.
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spelling doaj-art-0c63e76ef3fe4fcebdb94d1feeeb82bf2025-08-20T03:32:47ZengSAGE PublishingTumor Biology1423-03802017-08-013910.1177/1010428317698362Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosisFereshteh Ahmadinejad0Seyed Javad Mowla1Mohammad-Amin Honardoost2Mostafa Gholami Arjenaki3Mohammad Moazeni-Bistgani4Soleyman Kheiri5Hossein Teimori6Cellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, IranDepartment of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, IranDepartment of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, SingaporeClinical Biochemistry Research Center, Shahrekord University of Medical Sciences, Shahrekord, IranDepartment of Surgery, Shahrekord University of Medical Sciences, Shahrekord, IranDepartment of Epidemiology and Biostatistics, School of Health, Shahrekord University of Medical Sciences, Shahrekord, IranCellular and Molecular Research Center, Shahrekord University of Medical Sciences, Shahrekord, IranBreast cancer is considered as the most prevalent malignancy in women worldwide. Despite emergence of several prognosticators for better management of patients, there are still limitations for their clinical application due to the complexity of breast tumors, and therefore, new biomarkers for better prognosis of clinical outcomes would be of the great essence. MicroRNAs are highly conserved small non-coding regulatory RNAs involved in post-transcriptional regulating of gene expression during different cellular mechanisms. Accumulating studies suggest that miR-218 plays a multifunctional role in various cancer types and different stages. Here, to address prognostic significance of miR-218 in breast cancer, we investigate the expression profile of miR-218 and B-cell-specific Moloney murine leukemia virus integration site 1 ( BMI1 ) gene, as one of the putative targets of miR-218, in 33 paired breast tumors and their adjacent normal tissues with respect to the clinicopathological features of patients using quantitative real-time polymerase chain reaction. The correlation of both miR-218 and BMI1 gene expression with overall survival of breast cancer patients was also examined recruiting OncoLNC data portal. Finally, to better understand biological function of miR-218 in breast cancer, we performed in silico Gene Ontology and signaling pathway enrichment analysis on miR-218 targetome. According to our data, significant elevation of the expression of miR-218 and downregulation of BMI1 were observed in clinical breast cancer specimens compared with normal tissues ( p  < 0.0001). The lower expression of miR-218 was associated with lymph node metastases, higher grades, and poorer prognosis (logrank p  = 0.00988), whereas no significant difference in overall survival was observed between patients with higher and lower expression of BMI1 (logrank p  = 0.254). These findings suggest that miR-218 expression profiling might be clinically applicable as a prognostic biomarker in breast cancer. In addition, our in silico enrichment analyses revealed that the association of miR-218 expression with breast cancer prognosis might be through its involvement in endocytosis and gap junction biological pathways.https://doi.org/10.1177/1010428317698362
spellingShingle Fereshteh Ahmadinejad
Seyed Javad Mowla
Mohammad-Amin Honardoost
Mostafa Gholami Arjenaki
Mohammad Moazeni-Bistgani
Soleyman Kheiri
Hossein Teimori
Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis
Tumor Biology
title Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis
title_full Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis
title_fullStr Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis
title_full_unstemmed Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis
title_short Lower expression of miR-218 in human breast cancer is associated with lymph node metastases, higher grades, and poorer prognosis
title_sort lower expression of mir 218 in human breast cancer is associated with lymph node metastases higher grades and poorer prognosis
url https://doi.org/10.1177/1010428317698362
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