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

Abstract 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.
PMID
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Authors

Mayor MeshTerms
Keywords

BMI1

Breast cancer

miR-218

signaling pathway

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28857013
OWN - NLM
STAT- MEDLINE
DA  - 20170831
DCOM- 20170908
LR  - 20170908
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 8
DP  - 2017 Aug
TI  - Lower expression of miR-218 in human breast cancer is associated with lymph node 
      metastases, higher grades, and poorer prognosis.
PG  - 1010428317698362
LID - 10.1177/1010428317698362 [doi]
AB  - 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 &lt; 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.
FAU - Ahmadinejad, Fereshteh
AU  - Ahmadinejad F
AD  - 1 Cellular and Molecular Research Center, Shahrekord University of Medical
      Sciences, Shahrekord, Iran.
FAU - Mowla, Seyed Javad
AU  - Mowla SJ
AD  - 2 Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat
      Modares University, Tehran, Iran.
FAU - Honardoost, Mohammad-Amin
AU  - Honardoost MA
AD  - 3 Division of Cellular and Molecular Biology, Department of Biology, Faculty of
      Science, University of Isfahan, Isfahan, Iran.
AD  - 4 Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore,
      A*STAR (Agency for Science, Technology and Research), Singapore.
AD  - 5 Department of Physiology, Yong Loo Lin School of Medicine, National University 
      of Singapore, Singapore.
FAU - Arjenaki, Mostafa Gholami
AU  - Arjenaki MG
AD  - 6 Clinical Biochemistry Research Center, Shahrekord University of Medical
      Sciences, Shahrekord, Iran.
FAU - Moazeni-Bistgani, Mohammad
AU  - Moazeni-Bistgani M
AD  - 7 Department of Surgery, Shahrekord University of Medical Sciences, Shahrekord,
      Iran.
FAU - Kheiri, Soleyman
AU  - Kheiri S
AD  - 8 Department of Epidemiology and Biostatistics, School of Health, Shahrekord
      University of Medical Sciences, Shahrekord, Iran.
FAU - Teimori, Hossein
AU  - Teimori H
AD  - 1 Cellular and Molecular Research Center, Shahrekord University of Medical
      Sciences, Shahrekord, Iran.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MIRN218 microRNA, human)
RN  - 0 (MicroRNAs)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Breast Neoplasms/*genetics/pathology
MH  - Breast Neoplasms, Male/*genetics/pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Lymphatic Metastasis
MH  - Male
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Neoplasm Grading
MH  - Prognosis
OTO - NOTNLM
OT  - BMI1
OT  - Breast cancer
OT  - miR-218
OT  - signaling pathway
EDAT- 2017/09/01 06:00
MHDA- 2017/09/09 06:00
CRDT- 2017/09/01 06:00
AID - 10.1177/1010428317698362 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Aug;39(8):1010428317698362. doi: 10.1177/1010428317698362.