Lee Bongyong, Mazar Joseph, Aftab Muhammad N, Qi Feng, Shelley John, Li Jian-Liang, Govindarajan Subramaniam, Valerio Felipe, Rivera Inoel, Thurn Tadzia, Tran Tien Anh, Kameh Darian, Patel Vipul, Perera Ranjan J
J Mol Diagn. 2014 Nov;16(6):615-26. doi: 10.1016/j.jmoldx.2014.06.009.
Prostate cancer is one of the leading causes of mortality among US males. There is an urgent unmet need to develop sensitive and specific biomarkers for the early detection of prostate cancer to reduce overtreatment and accompanying morbidity. We identified a group of differentially expressed long noncoding RNAs in prostate cancer cell lines and patient samples and further characterized six long noncoding RNAs (AK024556, XLOC_007697, LOC100287482, XLOC_005327, XLOC_008559, and XLOC_009911) in prostatic adenocarcinoma tissue samples (Gleason score >6.0) and compared them with matched normal (healthy) tissues. Interestingly, these markers were also successfully detected in patient urine samples and were found to be up-regulated when compared with normal (healthy) urine. AK024556 (SPRY4-IT1) was highly up-regulated in human prostate cancer cell line PC3 but not in LNCaP, and siRNA knockdown of SPRY4-IT1 in PC3 cells inhibited cell proliferation and invasion and increased cell apoptosis. Chromogenic in situ hybridization assay was developed to detect long noncoding RNAs in primary prostatic adenocarcinoma tissue samples, paving the way for clinical diagnostics. We believe that these results will set the stage for more extensive studies to develop novel long noncoding RNA-based diagnostic assays for early prostate cancer detection and will help to distinguish benign prostate cancer from precancerous lesions.
前列腺癌是美国男性死亡的主要原因之一。迫切需要开发敏感且特异的生物标志物用于前列腺癌的早期检测,以减少过度治疗及随之而来的发病率。我们在前列腺癌细胞系和患者样本中鉴定出一组差异表达的长链非编码RNA,并进一步对前列腺腺癌组织样本(Gleason评分>6.0)中的6种长链非编码RNA(AK024556、XLOC_007697、LOC100287482、XLOC_005327、XLOC_008559和XLOC_009911)进行了表征,并将它们与匹配的正常(健康)组织进行比较。有趣的是,这些标志物在患者尿液样本中也被成功检测到,并且与正常(健康)尿液相比发现其表达上调。AK024556(SPRY4-IT1)在人前列腺癌细胞系PC3中高度上调,但在LNCaP中未上调,并且在PC3细胞中对SPRY4-IT1进行siRNA敲低可抑制细胞增殖和侵袭并增加细胞凋亡。开发了显色原位杂交检测法以检测原发性前列腺腺癌组织样本中的长链非编码RNA,为临床诊断铺平了道路。我们相信这些结果将为开展更广泛的研究奠定基础,以开发基于新型长链非编码RNA的早期前列腺癌检测诊断方法,并有助于区分良性前列腺癌与癌前病变。