Cargando…

High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer

Most breast cancer (BC) patients succumb to metastatic disease. MiR-34a is a well-known tumor suppressive microRNA which exerts its anti-cancer functions by playing a role in p53, apoptosis induction, and epithelial-mesenchymal transition (EMT) suppression. Molecular Taxonomy of Breast Cancer Intern...

Descripción completa

Detalles Bibliográficos
Autores principales: Tokumaru, Yoshihisa, Katsuta, Eriko, Oshi, Masanori, Sporn, Judith C., Yan, Li, Le, Lan, Matsuhashi, Nobuhisa, Futamura, Manabu, Akao, Yukihiro, Yoshida, Kazuhiro, Takabe, Kazuaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246662/
https://www.ncbi.nlm.nih.gov/pubmed/32357442
http://dx.doi.org/10.3390/ijms21093045
_version_ 1783537998907834368
author Tokumaru, Yoshihisa
Katsuta, Eriko
Oshi, Masanori
Sporn, Judith C.
Yan, Li
Le, Lan
Matsuhashi, Nobuhisa
Futamura, Manabu
Akao, Yukihiro
Yoshida, Kazuhiro
Takabe, Kazuaki
author_facet Tokumaru, Yoshihisa
Katsuta, Eriko
Oshi, Masanori
Sporn, Judith C.
Yan, Li
Le, Lan
Matsuhashi, Nobuhisa
Futamura, Manabu
Akao, Yukihiro
Yoshida, Kazuhiro
Takabe, Kazuaki
author_sort Tokumaru, Yoshihisa
collection PubMed
description Most breast cancer (BC) patients succumb to metastatic disease. MiR-34a is a well-known tumor suppressive microRNA which exerts its anti-cancer functions by playing a role in p53, apoptosis induction, and epithelial-mesenchymal transition (EMT) suppression. Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) cohorts were used to test our hypothesis that miR-34a high BCs translate to less aggressive cancer biology and better survival in large cohorts. There was no association between miR-34a expression levels and clinicopathological features of BC patients except for HER2 positivity. MiR-34a high expressing tumors were associated with lower Nottingham pathological grades and lower MKI67 expression. In agreement, high miR-34a tumors demonstrated lower GSVA scores of cell cycle and cell proliferation-related gene sets. High miR-34a tumors enriched the p53 pathway and apoptosis gene sets. Unexpectedly, high miR-34a tumors also associated with elevated EMT pathway score and ZEB1 and two expressions. MiR-34a expression did not associate with any distant metastasis. Further, high miR-34a tumors did not associate with better survival compared with miR-34a low tumors. In conclusion, the clinical relevance of miR-34a high expressing tumors was associated with suppressed cell proliferation, enhanced p53 pathway and apoptosis, but enhanced EMT and these findings did not reflect better survival outcomes in large BC patient cohorts.
format Online
Article
Text
id pubmed-7246662
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-72466622020-06-10 High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer Tokumaru, Yoshihisa Katsuta, Eriko Oshi, Masanori Sporn, Judith C. Yan, Li Le, Lan Matsuhashi, Nobuhisa Futamura, Manabu Akao, Yukihiro Yoshida, Kazuhiro Takabe, Kazuaki Int J Mol Sci Article Most breast cancer (BC) patients succumb to metastatic disease. MiR-34a is a well-known tumor suppressive microRNA which exerts its anti-cancer functions by playing a role in p53, apoptosis induction, and epithelial-mesenchymal transition (EMT) suppression. Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) cohorts were used to test our hypothesis that miR-34a high BCs translate to less aggressive cancer biology and better survival in large cohorts. There was no association between miR-34a expression levels and clinicopathological features of BC patients except for HER2 positivity. MiR-34a high expressing tumors were associated with lower Nottingham pathological grades and lower MKI67 expression. In agreement, high miR-34a tumors demonstrated lower GSVA scores of cell cycle and cell proliferation-related gene sets. High miR-34a tumors enriched the p53 pathway and apoptosis gene sets. Unexpectedly, high miR-34a tumors also associated with elevated EMT pathway score and ZEB1 and two expressions. MiR-34a expression did not associate with any distant metastasis. Further, high miR-34a tumors did not associate with better survival compared with miR-34a low tumors. In conclusion, the clinical relevance of miR-34a high expressing tumors was associated with suppressed cell proliferation, enhanced p53 pathway and apoptosis, but enhanced EMT and these findings did not reflect better survival outcomes in large BC patient cohorts. MDPI 2020-04-26 /pmc/articles/PMC7246662/ /pubmed/32357442 http://dx.doi.org/10.3390/ijms21093045 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tokumaru, Yoshihisa
Katsuta, Eriko
Oshi, Masanori
Sporn, Judith C.
Yan, Li
Le, Lan
Matsuhashi, Nobuhisa
Futamura, Manabu
Akao, Yukihiro
Yoshida, Kazuhiro
Takabe, Kazuaki
High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer
title High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer
title_full High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer
title_fullStr High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer
title_full_unstemmed High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer
title_short High Expression of miR-34a Associated with Less Aggressive Cancer Biology but Not with Survival in Breast Cancer
title_sort high expression of mir-34a associated with less aggressive cancer biology but not with survival in breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7246662/
https://www.ncbi.nlm.nih.gov/pubmed/32357442
http://dx.doi.org/10.3390/ijms21093045
work_keys_str_mv AT tokumaruyoshihisa highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT katsutaeriko highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT oshimasanori highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT spornjudithc highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT yanli highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT lelan highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT matsuhashinobuhisa highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT futamuramanabu highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT akaoyukihiro highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT yoshidakazuhiro highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer
AT takabekazuaki highexpressionofmir34aassociatedwithlessaggressivecancerbiologybutnotwithsurvivalinbreastcancer