BACKGROUND Retinoid acid induced 16 (RAI16) was reported to enhance tumorigenesis in hepatocellular carcinoma (HCC). The androgen receptor (AR) is a nuclear hormone receptor that functions as a critical oncogene in several cancer progressions. However, whether RAI16 is a candidate AR target gene that may involve in prostate cancer progression was unclear. MATERIALS & METHODS RAI16 expression was detected in prostate cancer cells with or without the AR agonist R1881 treatment by quantitative RT-PCR and Western blot. Direct AR binding to the RAI16 promoter was tested using AR chromatin immunoprecipitation (ChIP) and luciferase assay. Cell viability and colony formation assays in response to R1881 were analyzed in cells with RAI16 knockdown by specific siRNA. RESULTS The expression of RAI16 was high in LNCaP(AI), LNCaP(AD), C4-2 expressing AR, but low in Du145 and Pc-3 cells without AR expressing. In addition, the expression of RAI16 could be induced by 10 nM R1881 treatment LNCaP(AD) and C4-2 cells, but inhibited by AR specific siRNA treatment. Furthermore, AR binds directly to ARE3 (-2003~-1982bp) of RAI16 promoter region by ChIP and luciferase assay. RAI16 knockdown inhibited the enhancement of cell viability and colony formation of AR stimulation. CONCLUSIONS We demonstrate for the first time that RAI16 is a direct target gene of AR. RAI16 may involved in cell growth of prostate cancer cells in response to AR signaling.

中文翻译：

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类维生素A酸诱导16作为前列腺癌细胞中新的雄激素受体靶标的鉴定。

背景技术据报道，类维生素A诱导的16（RAI16）可增强肝细胞癌（HCC）的肿瘤发生。雄激素受体（AR）是一种核激素受体，在几种癌症的进展过程中起着至关重要的癌基因的作用。但是，RAI16是否是可能参与前列腺癌进展的候选AR目标基因尚不清楚。材料与方法通过定量RT-PCR和Western印迹，在有或没有AR激动剂R1881处理的前列腺癌细胞中检测到RAI16表达。使用AR染色质免疫沉淀（ChIP）和荧光素酶测定法测试了直接AR与RAI16启动子的结合。在具有RAI16抑制作用的细胞中，通过特异性siRNA分析了响应R1881的细胞活力和集落形成分析。结果RAI16在表达AR的LNCaP（AI），LNCaP（AD），C4-2中高表达。但在不表达AR的Du145和Pc-3细胞中含量较低。此外，RAI16的表达可被10nM R1881处理的LNCaP（AD）和C4-2细胞诱导，但被AR特异性siRNA处理抑制。此外，通过ChIP和荧光素酶测定，AR直接结合至RAI16启动子区域的ARE3（-2003〜-1982bp）。RAI16组合式抑制细胞活力的增强和AR刺激的集落形成。结论我们首次证明RAI16是AR的直接靶基因。RAI16可能参与响应AR信号的前列腺癌细胞的生长。通过ChIP和荧光素酶测定，AR直接与RAI16启动子区域的ARE3（-2003〜-1982bp）结合。RAI16组合式抑制细胞活力的增强和AR刺激的集落形成。结论我们首次证明RAI16是AR的直接靶基因。RAI16可能参与响应AR信号的前列腺癌细胞的生长。通过ChIP和荧光素酶测定，AR直接与RAI16启动子区域的ARE3（-2003〜-1982bp）结合。RAI16组合式抑制细胞活力的增强和AR刺激的集落形成。结论我们首次证明RAI16是AR的直接靶基因。RAI16可能参与响应AR信号的前列腺癌细胞的生长。