MicroRNAs 143 and 145 may be involved in benign prostatic hyperplasia pathogenesis through regulation of target genes and proteins.
OBJECTIVE
The aim of this study was to analyze the roles of miR-143 and miR-145, as well as the gene and protein expression of their targets (KRAS, ERK5, MAP3K3, and MAP4K4) in the pathogenesis of benign prostatic hyperplasia (BPH).


METHODS
We analyzed the specimens of 44 patients diagnosed with BPH who underwent surgical treatment. The control group consisted of prostate samples from 2 young patients who were organ donors. miRNAs and their target genes were assessed using real-time polymerase chain reaction (qRT-PCR), and protein levels were assessed by Western blotting.


RESULTS
miR-143 and miR-145 were overexpressed in, respectively, 62.5% and 73.8% of the cases. The ERK5 and MAP4K4 genes were underexpressed respectively in 59.4% and 100% of the BPH samples, whereas KRAS and MAP3K3 were overexpressed respectively in 79.4% and 61.5% of the samples. Increased protein expression was found for both KRAS (4,312.2 luminance/area) and MAP3K3 (7,461.7 luminance/area), while the ERK5 protein was more abundant in the samples from patients with prostate larger than 60 grams (p=0.019).


CONCLUSIONS
The overexpression of miR-143 and miR-145 in BPH samples suggests an association with the pathogenesis of the disease; additionally, the latter miRNA may act through the inhibition of MAP4K4. KRAS and MAP3K3 overexpression may also be associated with BPH pathogenesis. Further analyses are necessary to confirm these results.
Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Sao Paulo - Brazil.
Nayara I
NI
Viana
Sabrina T
ST
Reis
Nelson G
NG
Dip
Denis R
DR
Morais
Caio M
CM
Moura
Iran A
IA
Silva
Betina
B
Katz
Miguel
M
Srougi
Katia R M
KR
Leite
Alberto A
AA
Antunes
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000096:biosynthesis / Q000235:genetics; D048748:MAP Kinase Kinase Kinase 3 / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics*; D008875:Middle Aged; D048054:Mitogen-Activated Protein Kinase 7 / Q000096:biosynthesis / Q000235:genetics; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000096:biosynthesis / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; C117307:KRAS protein, human; C542359:MIRN143 microRNA, human; C541010:MIRN145 microRNA, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C117090:MAP4K4 protein, human; D017346:Protein Serine-Threonine Kinases; D048054:Mitogen-Activated Protein Kinase 7; D048748:MAP Kinase Kinase Kinase 3; C482625:MAP3K3 protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins