Identification of androgen-responsive microRNAs and androgen-related genes in breast cancer.
BACKGROUND
Androgen receptors (ARs) are expressed in many breast cancer cells, but the mechanism of action of androgens is not as well-characterized as in other cell types. The study of microRNAs has recently provided with important insights into the biology of hormone-dependent cancer.


METHODS
We attempted to identify microRNAs induced by dihydrotestosterone in an AR-positive cell line. We examined a possible correlation among microRNAs, target genes, and ARs in breast cancer tissues using immunohistochemistry and laser capture microscopy.


RESULTS
Our analysis demonstrated that miR-363 and its possible target IQ motif and WD repeats-1 (IQWD1) are involved in a microRNA-mRNA pathway related to the mechanism of action of androgens. Our analyses showed that a high tumor level of IQWD1 in patients with breast cancer was significantly associated with adverse clinical outcomes.


CONCLUSIONS
Our findings indicated that the recruitment of IQWD1 to ARs may be a prerequisite for the growth stimulation by androgens through ARs in breast cancer cells.
2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575 Japan. hsasano@patholo2.med.tohoku.ac.jp.
Kiichiroh
K
Nakano
Yasuhiro
Y
Miki
Shuko
S
Hata
Akiko
A
Ebata
Kiyoshi
K
Takagi
Keely M
KM
McNamara
Minako
M
Sakurai
Mariko
M
Masuda
Hisashi
H
Hirakawa
Takanori
T
Ishida
Takashi
T
Suzuki
Noriaki
N
Ohuchi
Hironobu
H
Sasano
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000494:pharmacology; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D049109:Cell Proliferation; D013196:Dihydrotestosterone / Q000494:pharmacology*; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D007124:Immunoenzyme Techniques; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured; D055815:Young Adult
D048868:Adaptor Proteins, Signal Transducing; D000728:Androgens; D014408:Biomarkers, Tumor; C501825:DCAF6 protein, human; C574861:MIRN363 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011944:Receptors, Androgen; D013196:Dihydrotestosterone
Breast cancer; IQWD1; androgen; microRNA