Wang Chunyang, Tao Weiyang, Ni Shaobin, Chen Qiyin, Zhao Zhongshan, Ma Li, Fu Yiming, Jiao Zhixing
Department of Urology, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Cancer Sci. 2015 Apr;106(4):375-82. doi: 10.1111/cas.12626. Epub 2015 Mar 16.
Prostate cancer (PCa) prevails as the most commonly diagnosed malignancy in men and the third leading cause of cancer-related deaths in developed countries. One of the distinct characteristics of prostate cancer is overexpression of the small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1), and the upregulation of SENP1 contributes to the malignant progression and cell proliferation of PCa. Previous studies have shown that the expression of microRNA-145 (miRNA-145) was extensively deregulated in PCa cell lines and primary clinical prostate cancer samples. Independent target prediction methods have indicated that the 3'-untranslated region of SENP1 mRNA is a potential target of miR-145. Here we found that low expression of miR-145 was correlated with high expression of SENP1 in PCa cell line PC-3. The transient introduction of miR-145 caused cell cycle arrest in PC-3 cells, and the opposite effect was observed when miR-145 inhibitor was transfected. Further studies revealed that the SENP1 3'-untranslated region was a regulative target of miR-145 in vitro. MicroRNA-145 also suppressed tumor formation in vivo in nude mice. Taken together, miR-145 plays an important role in tumorigenesis of PCa through interfering SENP1.
前列腺癌（PCa）是男性中最常被诊断出的恶性肿瘤，也是发达国家癌症相关死亡的第三大主要原因。前列腺癌的一个显著特征是小泛素样修饰物（SUMO）特异性蛋白酶1（SENP1）的过度表达，而SENP1的上调促进了PCa的恶性进展和细胞增殖。先前的研究表明，微小RNA-145（miRNA-145）的表达在PCa细胞系和原发性临床前列腺癌样本中广泛失调。独立的靶标预测方法表明，SENP1 mRNA的3'非翻译区是miR-145的潜在靶标。在此我们发现，在PCa细胞系PC-3中，miR-145的低表达与SENP1的高表达相关。miR-145的瞬时导入导致PC-3细胞的细胞周期停滞，而转染miR-145抑制剂时则观察到相反的效果。进一步的研究表明，SENP1的3'非翻译区在体外是miR-145的调控靶标。MicroRNA-145在裸鼠体内也抑制肿瘤形成。综上所述，miR-145通过干扰SENP1在PCa的肿瘤发生中起重要作用。
