LncRNA PCGEM1和雄激素受体在前列腺癌中的共定位表达及临床意义

摘要

背景与目的：长链非编码RNA(long non-coding RNA，lncRNA)可参与肿瘤调控，有研究提示lncRNA PCGEM1可能影响雄激素受体(androgen receptor，AR)通路。本研究拟检测前列腺癌lncRNA PCGEM1和AR的表达情况，探讨其在前列腺癌中的表达及意义。方法：构建RNA核酸探针，应用荧光原位杂交(lfuores-cencein situ hybridization，FISH)技术检测前列腺癌lncRNA PCGEM1的表达情况，并使用荧光免疫组织化学技术检测前列腺癌AR的表达；采用RNA-pull down技术检测PCGEM1和AR的共同作用。结果：依赖AR的LNCaP细胞的PCGEM1表达水平显著高于非AR依赖性的PC3和DU145细胞，差异有统计学意义(P<0.01)。前列腺癌组织中PCGEM1的表达与AR表达程度显著相关。与良性前列腺肿瘤相比，转移性肿瘤中的PCGEM1细胞核内定位显著不同，雄激素去势显著影响PCGEM1的表达及细胞内定位。而共定位检测发现，PCGEM1与AR之间存在一定程度的共定位现象。结论：本研究通过FISH研究发现，PCGEM1表达在雄激素去势条件下显著上调，而在转移性前列腺癌中，PCGEM1和AR的共定位表达表明，lncRNA PCGEM1和AR相互作用可能共同参与调控前列腺癌的恶性进展及转移。%Background and purpose:Long non-coding RNA (lncRNA) could be an important player in cancer biology. Recent studies showed that lncRNA PCGEM1 might be important in the regulation of androgen recep-tor (AR) signaling pathway. We tried to observe the expressions of lncRNA PCGEM1 and AR in prostate cancer, and investigate their role and signiifcance in prostate cancer genesis and progress.Methods:The expression of lncRNA PCGEM1 was observed in prostate cancer by lfuorescencein situ hybridization (FISH) technique. Then detection of AR was performed by immunolfuorescence histochemistry methods. Their co-effective role was checked by RNA pull-down technique.Results:Compared with the AR-independent cell line such as PC3 or DU145, AR-dependent cell line such as LNCaP showed much higher expression of lncRNA PCGEM1 (P<0.01). PCGEM1 and AR could be co-localized in most of these prostate cancer samples, especially in the metastasis samples. Moreover, androgen deprivation promoted the translocation of PCGEM1 into nucleus. RNA pull-down results also proved the co-effective role of PCGEM1 and AR.Conclusion:This study showed that lncRNA PCGEM1 was highly expressed in metastatic prostate cancer. It was related to the progress and malignant behavior of the prostate cancer. Its co-localization with AR may play an important role in prostate cancer genesis and progress.