Anchi Takashi, Tamura Kenji, Furihata Mutsuo, Satake Hirofumi, Sakoda Hatsune, Kawada Chiaki, Kamei Maiko, Shimamoto Tsutomu, Fukuhara Hideo, Fukata Satoshi, Ashida Shingo, Karashima Takashi, Yamasaki Ichiro, Yasuda Masaharu, Kamada Masayuki, Inoue Keiji, Shuin Taro
Department of Urology, Kochi Medical School, Kochi University, Nankoku, Kochi 783-8505.
Oncol Lett. 2012 Feb;3(2):264-268. doi: 10.3892/ol.2011.505. Epub 2011 Dec 1.
Clinically high-grade prostate cancers (PC) with high Gleason scores of 8-10 exhibit rapid growth and are more likely to spread beyond the prostate. These cancer types demonstrate a poor response to androgen deprivation therapy and eventually acquire a castration-resistant phenotype. To identify novel molecular cancer drug targets, we previously analyzed the gene expression profiles of high-grade PC using a cDNA microarray combined with laser microbeam microdissection and found a number of genes that are transactivated in high-grade PC. Among these genes, we report the identification of a novel molecular target, small nuclear ribonucleoprotein polypeptide E (SNRPE). Semi-quantitative RT-PCR confirmed that SNRPE is overexpressed in high-grade PC cells compared with normal prostatic epithelial cells. Knockdown of SNRPE expression by short interfering RNA (siRNA) resulted in the marked suppression of PC cell proliferation. By contrast, SNRPE overexpression promoted PC cell proliferation, indicating its oncogenic effects. Furthermore, we demonstrated that SNRPE regulates androgen receptor (AR) mRNA expression in PC cells. Knockdown of SNRPE expression by siRNA resulted in the marked suppression of AR and its downstream target genes at the mRNA level. We suggest that the regulation of AR expression by SNRPE is essential for cell proliferation and progression of high-grade PC and that it may be a novel molecular target for cancer drugs.
临床上高分级前列腺癌（PC），其Gleason评分高达8 - 10分，生长迅速，且更有可能扩散至前列腺以外。这些癌症类型对雄激素剥夺疗法反应不佳，并最终获得去势抵抗表型。为了确定新的分子癌症药物靶点，我们之前使用cDNA微阵列结合激光微束显微切割技术分析了高分级PC的基因表达谱，发现了一些在高分级PC中被反式激活的基因。在这些基因中，我们报告鉴定出一个新的分子靶点，小核核糖核蛋白多肽E（SNRPE）。半定量逆转录聚合酶链反应（RT-PCR）证实，与正常前列腺上皮细胞相比，SNRPE在高分级PC细胞中过表达。通过短干扰RNA（siRNA）敲低SNRPE的表达导致PC细胞增殖受到显著抑制。相反，SNRPE的过表达促进了PC细胞增殖，表明其致癌作用。此外，我们证明SNRPE在PC细胞中调节雄激素受体（AR）mRNA的表达。通过siRNA敲低SNRPE的表达导致在mRNA水平上AR及其下游靶基因受到显著抑制。我们认为，SNRPE对AR表达的调节对于高分级PC的细胞增殖和进展至关重要，并且它可能是癌症药物的一个新的分子靶点。
