PMID- 25123132
OWN - NLM
STAT- MEDLINE
DCOM- 20150313
LR  - 20211021
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 35
IP  - 11
DP  - 2014 Nov
TI  - Overexpression of miR-146a in basal-like breast cancer cells confers enhanced 
      tumorigenic potential in association with altered p53 status.
PG  - 2567-75
LID - 10.1093/carcin/bgu175 [doi]
AB  - The tumor suppressor p53 is the most frequently mutated gene in human cancers, 
      mutated in 25-30% of breast cancers. However, mutation rates differ according to 
      breast cancer subtype, being more prevalent in aggressive estrogen 
      receptor-negative tumors and basal-like and HER2-amplified subtypes. This 
      heterogeneity suggests that p53 may function differently across breast cancer 
      subtypes. We used RNAi-mediated p53 knockdown (KD) and antagomir-mediated KD of 
      microRNAs to study how gene expression and cellular response to p53 loss differ 
      in luminal versus basal-like breast cancer. As expected, p53 loss caused 
      downregulation of established p53 targets (e.g. p21 and miR-34 family) and 
      increased proliferation in both luminal and basal-like cell lines. However, some 
      p53-dependent changes were subtype specific, including expression of miR-134, 
      miR-146a and miR-181b. To study the cellular response to miR-146a upregulation in 
      p53-impaired basal-like lines, antagomir KD of miR-146a was performed. KD of 
      miR-146a caused decreased proliferation and increased apoptosis, effectively 
      ablating the effects of p53 loss. Furthermore, we found that miR-146a 
      upregulation decreased NF-kappaB expression and downregulated the NF-kappaB-dependent 
      extrinsic apoptotic pathway (including tumor necrosis factor, FADD and TRADD) and 
      antagomir-mediated miR-146a KD restored expression of these components, 
      suggesting a plausible mechanism for miR-146a-dependent cellular responses. These 
      findings are relevant to human basal-like tumor progression in vivo, since 
      miR-146a is highly expressed in p53 mutant basal-like breast cancers. These 
      findings suggest that targeting miR-146a expression may have value for altering 
      the aggressiveness of p53 mutant basal-like tumors.
CI  - (c) The Author 2014. Published by Oxford University Press. All rights reserved. For 
      Permissions, please email: journals.permissions@oup.com.
FAU - Sandhu, Rupninder
AU  - Sandhu R
AD  - UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA.
FAU - Rein, Jessica
AU  - Rein J
AD  - Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel 
      Hill, NC 27599, USA.
FAU - D'Arcy, Monica
AU  - D'Arcy M
AD  - Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel 
      Hill, NC 27599, USA.
FAU - Herschkowitz, Jason I
AU  - Herschkowitz JI
AD  - Department of Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, TX 77030, USA and.
FAU - Hoadley, Katherine A
AU  - Hoadley KA
AD  - UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA.
FAU - Troester, Melissa A
AU  - Troester MA
AD  - UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA, 
      Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel 
      Hill, NC 27599, USA, Department of Pathology and Laboratory Medicine, University 
      of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA troester@unc.edu.
LA  - eng
GR  - P30 ES010126/ES/NIEHS NIH HHS/United States
GR  - R25 CA057726/CA/NCI NIH HHS/United States
GR  - U01-CA-179715/CA/NCI NIH HHS/United States
GR  - U01-ES-019472/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20140814
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (MIRN146 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Suppressor Protein p53)
SB  - IM
MH  - Breast Neoplasms/*genetics/pathology
MH  - Carcinogenesis/*genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MCF-7 Cells
MH  - MicroRNAs/*biosynthesis/genetics
MH  - Mutation
MH  - NF-kappa B/metabolism
MH  - RNA Interference
MH  - Signal Transduction/genetics
MH  - Tumor Suppressor Protein p53/*genetics
PMC - PMC4288116
EDAT- 2014/08/16 06:00
MHDA- 2015/03/17 06:00
PMCR- 2015/11/01
CRDT- 2014/08/16 06:00
PHST- 2014/08/16 06:00 [entrez]
PHST- 2014/08/16 06:00 [pubmed]
PHST- 2015/03/17 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - bgu175 [pii]
AID - 10.1093/carcin/bgu175 [doi]
PST - ppublish
SO  - Carcinogenesis. 2014 Nov;35(11):2567-75. doi: 10.1093/carcin/bgu175. Epub 2014 
      Aug 14.