Viana Nayara I, Reis Sabrina T, Dip Nelson G, Morais Denis R, Moura Caio M, Silva Iran A, Katz Betina, Srougi Miguel, Leite Katia R M, Antunes Alberto A
Laboratory of Medical Investigation (LIM55), University of Sao Paulo Medical School, Sao Paulo - Brazil.
Int J Biol Markers. 2014 Sep 30;29(3):e246-52. doi: 10.5301/jbm.5000069.
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).
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.
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).
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.
本研究旨在分析miR - 143和miR - 145及其靶标(KRAS、ERK5、MAP3K3和MAP4K4)的基因和蛋白表达在良性前列腺增生(BPH)发病机制中的作用。
我们分析了44例接受手术治疗的BPH患者的标本。对照组由2名年轻器官捐献者的前列腺样本组成。使用实时聚合酶链反应(qRT - PCR)评估miRNAs及其靶基因,并通过蛋白质印迹法评估蛋白水平。
miR - 143和miR - 145分别在62.5%和73.8%的病例中过表达。ERK5和MAP4K4基因分别在59.4%和100%的BPH样本中表达下调,而KRAS和MAP3K3分别在79.4%和61.5%的样本中过表达。发现KRAS(4312.2亮度/面积)和MAP3K3(7461.7亮度/面积)的蛋白表达均增加,而前列腺大于60克的患者样本中ERK5蛋白含量更高(p = 0.019)。
BPH样本中miR - 143和miR - 145的过表达表明其与疾病发病机制有关;此外,后一种miRNA可能通过抑制MAP4K4发挥作用。KRAS和MAP3K3的过表达也可能与BPH发病机制有关。需要进一步分析以证实这些结果。