Long Noncoding RNAs as Putative Biomarkers for Prostate Cancer Detection
Long Noncoding RNAs as Putative Biomarkers for Prostate Cancer Detection
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DOI：
10.1016/j.jmoldx.2014.06.009
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发表时间：
2014-11-01
影响因子：
4.1
通讯作者：
Perera, Ranjan J.
中科院分区：
文献类型：
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作者：
Lee, Bongyong;Mazar, Joseph;Perera, Ranjan J.
前列腺癌是美国男性死亡的主要原因之一。目前迫切需要开发敏感和特异的生物标志物来早期检测前列腺癌，以减少过度治疗和伴随的发病率。我们在前列腺癌细胞系和患者样本中鉴定了一组差异表达的长链非编码RNA，并进一步表征了前列腺癌组织样本（格里森评分> 6.0）和将它们与匹配的正常（健康）组织进行比较。有趣的是，这些标记物也在患者尿液样本中成功检测到，并且与正常（健康）尿液相比，这些标记物的表达上调。 AK024556 (SPRY4-IT1) 在人前列腺癌细胞 PC3 中高度上调，但在 LNCaP 中则不然，并且 PC3 细胞中 SPRY4-IT1 的 siRNA 敲低可抑制细胞增殖和侵袭并增加细胞凋亡。显色原位杂交测定被开发用于检测原发性前列腺腺癌组织样本中的长非编码RNA，为临床诊断铺平了道路。我们相信，这些结果将为更广泛的研究奠定基础，以开发用于早期前列腺癌检测的新型基于长链非编码RNA的诊断测定法，并将有助于区分良性前列腺癌和癌前病变。
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 over-treatment 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 tine 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.