Janiak Marek, Paskal Wiktor, Rak Beata, Garbicz Filip, Jarema Robert, Sikora Krzysztof, Włodarski Paweł
The Department of Histology and Embryology, Medical University of Warsaw, Warsaw, Poland.
Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland.
APMIS. 2017 Feb;125(2):101-105. doi: 10.1111/apm.12638. Epub 2016 Dec 28.
In prostate cancer TIMP4 expression level fluctuates with tumor progression. The mechanism and factors influencing its expression remain unclear. The aim of the study was to test the hypothesis on regulation of TIMP4 by microRNA-200b-3p. The levels of TIMP4 and miR-200b-3p expression were determined by real time PCR in 27 prostate carcinomas and eight benign prostatic hyperplasia samples. We found that miR-200b-3p positively correlated with TIMP4 expression in cancer samples (r = 0.46; p < 0.02). Moreover, mean miR-200b-3p level and TIMP4 expression were both higher in cancer tissues compared to benign prostatic hyperplasia samples (p > 0.05). Next, to test probable mechanisms of the regulation androgen-sensitive human prostate adenocarcinoma cells (LNCaP) were transfected with synthetic-miR-200b-3p or its synthetic antagonist. Modulation of miR-200b-3p in LNCaP cells had an impact on TIMP4 expression confirming the observation made in analyzed clinical samples. Two targets of miR-200b-3p: ZEB1 and ETS1 were investigated subsequently as potential regulators of TIMP4, however, no effect of their modulation on TIMP4 expression in LNCaP cells was found. Concluding, miR-200b-3p mediates regulation of TIMP4 expression in prostate cancer but exact mechanism needs to be investigated.
在前列腺癌中，TIMP4的表达水平随肿瘤进展而波动。影响其表达的机制和因素仍不清楚。本研究的目的是验证microRNA-200b-3p对TIMP4调控的假说。通过实时PCR测定了27例前列腺癌和8例良性前列腺增生样本中TIMP4和miR-200b-3p的表达水平。我们发现，在癌症样本中miR-200b-3p与TIMP4表达呈正相关（r = 0.46；p < 0.02）。此外，与良性前列腺增生样本相比，癌症组织中的平均miR-200b-3p水平和TIMP4表达均更高（p > 0.05）。接下来，为了测试可能的调控机制，用合成的miR-200b-3p或其合成拮抗剂转染雄激素敏感的人前列腺腺癌细胞（LNCaP）。LNCaP细胞中miR-200b-3p的调节对TIMP4表达有影响，这证实了在分析的临床样本中的观察结果。随后研究了miR-200b-3p的两个靶标：ZEB1和ETS1作为TIMP4的潜在调节因子，然而，未发现它们的调节对LNCaP细胞中TIMP4表达有影响。总之，miR-200b-3p介导前列腺癌中TIMP4表达的调控，但确切机制有待研究。
