MicroRNA expression profiling in male and female familial breast cancer.
BACKGROUND
Gender-associated epigenetic alterations are poorly investigated in male and female familial breast cancer (fBC). MicroRNAs may contribute to the different biology in men and women particularly related to RASSF1A pathways.


METHODS
Microarray technology was used to evaluate miRNA profile in 24 male and 43 female fBC. Key results were validated using RT-qPCR in an external samples set. In vitro studies were carried out to verify microRNA-target gene interaction.


RESULTS
Pathway enrichment analysis with the 287 differentially expressed microRNAs revealed several signalling pathways differently regulated in male and female cases. Because we previously hypothesised a peculiar involvement of RASSF1A in male fBC pathogenesis, we focussed on the MAPK and the Hippo signalling pathways that are regulated by RASSF1A. Male miR-152 and miR-497 upregulation and RASSF1A and NORE1A interacting gene downregulation were observed, confirming a possible indirect interaction between miRNAs and the two genes.


CONCLUSIONS
For the first time, a different microRNA expression pattern in male and female fBC has been shown. Moreover, the importance of RASSF1A pathway in male fBC carcinogenesis has been confirmed, highlighting a possible role for miR-152 and miR-497 in controlling MAPK and Hippo signalling pathways, regulated by RASSF1A.
IRCCS 'Giovanni Paolo II', Molecular Genetics Laboratory, Viale Orazio Flacco 65, Bari 70124, Italy.
R
R
Pinto
IRCCS 'Giovanni Paolo II', Molecular Genetics Laboratory, Viale Orazio Flacco 65, Bari 70124, Italy.
S
S
De Summa
IRCCS 'Giovanni Paolo II', Molecular Genetics Laboratory, Viale Orazio Flacco 65, Bari 70124, Italy.
K
K
Danza
IRCCS 'Giovanni Paolo II', Anatomopathology Unit, Bari, Italy.
O
O
Popescu
IRCCS 'Giovanni Paolo II', Experimental Medical Oncology Unit, Bari, Italy.
A
A
Paradiso
IRCCS 'Casa Sollievo della Sofferenza', Medical Genetics Unit, San Giovanni Rotondo (FG), Italy.
L
L
Micale
IRCCS 'Casa Sollievo della Sofferenza', Medical Genetics Unit, San Giovanni Rotondo (FG), Italy.
G
G
Merla
IRCCS 'Casa Sollievo della Sofferenza', Medical Genetics Unit, San Giovanni Rotondo (FG), Italy.
O
O
Palumbo
IRCCS 'Casa Sollievo della Sofferenza', Medical Genetics Unit, San Giovanni Rotondo (FG), Italy.
M
M
Carella
IRCCS 'Giovanni Paolo II', Molecular Genetics Laboratory, Viale Orazio Flacco 65, Bari 70124, Italy.
S
S
Tommasi
D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D018567:Breast Neoplasms, Male / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D046228:Microarray Analysis; D015398:Signal Transduction
D035683:MicroRNAs