INhibitor of Growth protein 4 (ING4) is a potential chromatin modifier that has been implicated in several cancer-related processes. However, the role of ING4 in prostate cancer (PC) is largely unknown. This study aimed to assess ING4's role in global transcriptional regulation in PC cells to identify potential cellular processes associated with ING4 loss. RNA-Seq using next-generation sequencing (NGS) was used to identify altered genes in LNCaP PC cells following ING4 depletion. Ingenuity pathways analysis (IPA®) was applied to the data to highlight candidates, ING4-regulated pathways, networks and cellular processes. Selected genes were validated using RT-qPCR. RNA-Seq of LNCaP cells revealed a total of 159 differentially expressed genes (fold change ≥ 1.5 or ≤ - 1.5, FDR ≤ 0.05) following ING4 knockdown. RT-qPCR used to validate the expression level of selected genes was in agreement with RNA-Seq results. Key genes, unique pathways, and biological networks were identified using IPA® analysis. This is the first report of global gene regulation in PC cells by ING4. The resultant differential expression profile revealed the potential role of ING4 in PC pathogenesis possibly through modulation of key genes, pathways and biological networks that are central drivers of the disease. Collectively, these findings shed light on a novel transcriptional regulator of PC that ultimately may influence the disease progression and as a potential target in the disease therapy.

中文翻译：

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确定生长蛋白4抑制剂（ING4）作为前列腺癌治疗的潜在靶标。

生长蛋白4抑制剂（ING4）是一种潜在的染色质修饰剂，与多种癌症相关过程有关。但是，ING4在前列腺癌（PC）中的作用尚不清楚。这项研究旨在评估ING4在PC细胞中全球转录调控中的作用，以鉴定与ING4丢失相关的潜在细胞过程。使用下一代测序（NGS）的RNA-Seq用于鉴定ING4耗尽后LNCaP PC细胞中的基因改变。对数据进行了独创性途径分析（IPA®），以突出显示候选者，ING4调节的途径，网络和细胞过程。使用RT-qPCR验证选择的基因。ING4敲低后，LNCaP细胞的RNA-Seq显示共有159个差异表达的基因（倍数变化≥1.5或≤-1.5，FDR≤0.05）。用于验证所选基因表达水平的RT-qPCR与RNA-Seq结果一致。使用IPA®分析鉴定了关键基因，独特途径和生物网络。这是ING4对PC细胞进行全局基因调控的第一份报告。产生的差异表达谱揭示了ING4在PC发病机制中的潜在作用，可能是通过调节作为该疾病主要驱动力的关键基因，途径和生物学网络来实现的。这些发现共同揭示了PC的新型转录调控因子，该转录调控因子最终可能会影响疾病的进展并成为疾病治疗的潜在靶标。这是ING4对PC细胞进行全局基因调控的第一份报告。产生的差异表达谱揭示了ING4在PC发病机制中的潜在作用，可能是通过调节作为该疾病主要驱动力的关键基因，途径和生物学网络来实现的。这些发现共同揭示了PC的新型转录调控因子，该转录调控因子最终可能会影响疾病的进展并成为疾病治疗的潜在靶标。这是ING4对PC细胞进行全局基因调控的第一份报告。产生的差异表达谱揭示了ING4在PC发病机制中的潜在作用，可能是通过调节作为该疾病主要驱动力的关键基因，途径和生物学网络来实现的。这些发现共同揭示了PC的新型转录调控因子，该转录调控因子最终可能会影响疾病的进展并成为疾病治疗的潜在靶标。