PMID- 23492819
OWN - NLM
STAT- MEDLINE
DCOM- 20130930
LR  - 20220309
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Print)
IS  - 0143-3334 (Linking)
VI  - 34
IP  - 5
DP  - 2013 May
TI  - MicroRNA-93 regulates NRF2 expression and is associated with breast 
      carcinogenesis.
PG  - 1165-72
LID - 10.1093/carcin/bgt026 [doi]
AB  - MicroRNAs (miRNA) are small non-coding RNAs that regulate the expression of 
      approximately 60% of all human genes and play important roles in disease 
      processes. Recent studies have demonstrated a link between dysregulated 
      expression of miRNAs and breast carcinogenesis. Long-term estrogen exposure is 
      implicated in development of human breast cancers, yet underlying mechanisms 
      remain elusive. We have recently demonstrated that antioxidant vitamin C (vit C) 
      prevents estrogen-induced breast tumor development. In this study, we 
      investigated the role of vit C in the regulation of microRNA-93 (miR-93) and its 
      target gene(s) in a rat model of mammary carcinogenesis. Female August Copenhagen 
      Irish (ACI) rats were treated with vit C in the presence or absence of 
      17beta-estradiol (E2) for 8 months. We demonstrate an increased expression of the 
      miR-93 in E2-treated mammary tissues and in human breast cell lines and vit C 
      treatment reverted E2-mediated increase in miR-93 levels. MiRNA target prediction 
      programs suggest one of the target genes of miR-93 to be nuclear factor erythroid 
      2-related factor 2 (NRF2). In contrast with miR-93 expression, NRF2 protein 
      expression was significantly decreased in E2-treated mammary tissues, mammary 
      tumors, and in breast cancer cell lines, and its expression was significantly 
      increased after vit C treatment. Ectopic expression of miR-93 decreased protein 
      expression of NRF2 and NRF2-regulated genes. Furthermore, miR-93 decreased 
      apoptosis, increased colony formation, mammosphere formation, cell migration and 
      DNA damage in breast epithelial cells, whereas silencing of miR-93 in these cells 
      inhibited these carcinogenic processes. Taken together, our findings suggest an 
      oncogenic potential of miR-93 during E2-induced breast carcinogenesis.
FAU - Singh, Bhupendra
AU  - Singh B
AD  - Division of Pharmacology and Toxicology, School of Pharmacy, University of 
      Missouri-Kansas City, Kansas City, MO 64108, USA.
FAU - Ronghe, Amruta M
AU  - Ronghe AM
FAU - Chatterjee, Anwesha
AU  - Chatterjee A
FAU - Bhat, Nimee K
AU  - Bhat NK
FAU - Bhat, Hari K
AU  - Bhat HK
LA  - eng
GR  - CA109551/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130314
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Estrogens)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 4TI98Z838E (Estradiol)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects/genetics
MH  - Ascorbic Acid/pharmacology
MH  - Breast Neoplasms/*genetics/metabolism/*pathology/prevention & control
MH  - Cell Line, Tumor
MH  - Cell Movement/drug effects/genetics
MH  - Cell Transformation, Neoplastic/*genetics/metabolism/*pathology
MH  - DNA Damage
MH  - Estradiol/pharmacology
MH  - Estrogens/adverse effects
MH  - Female
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - NF-E2-Related Factor 2/*genetics/metabolism
MH  - Rats
MH  - Rats, Inbred ACI
MH  - Rats, Sprague-Dawley
MH  - Up-Regulation/drug effects
PMC - PMC3643421
EDAT- 2013/03/16 06:00
MHDA- 2013/10/01 06:00
PMCR- 2014/05/01
CRDT- 2013/03/16 06:00
PHST- 2013/03/16 06:00 [entrez]
PHST- 2013/03/16 06:00 [pubmed]
PHST- 2013/10/01 06:00 [medline]
PHST- 2014/05/01 00:00 [pmc-release]
AID - bgt026 [pii]
AID - 10.1093/carcin/bgt026 [doi]
PST - ppublish
SO  - Carcinogenesis. 2013 May;34(5):1165-72. doi: 10.1093/carcin/bgt026. Epub 2013 Mar 
      14.