Dysregulated hematological and neurological expressed 1-like (HN1L) has been implicated in carcinogenesis of difference cancers, including hepatocellular carcinoma and breast cancer. However, the role of HN1L in the progression of prostate cancer (PCA) remains unknown. Therefore, we aimed to investigate the role of HN1L in stemness and progression of PCA. The expression of HN1L in PCA tissues and cells was determined by quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blot analysis, and/or immunohistochemistry (IHC). CD133⁺ cells were sorted from PCA cells using magnetic fluorescence cell sorting technology and were considered as cancer stem cells (CSCs). Sphere formation assays, transwell assays, and animal experiments were conducted to assess cell stemness, migration, invasion, and in vivo tumorigenesis, respectively. The results showed that HN1L expression was higher in PCA tissues and cells as compared with normal tissues and cells, as well as in CD133⁺ cells as compared with CD133⁻ cells. HN1L knockdown significantly decreased the expression levels of CSC markers including OCT4 (POU class 5 homeobox 1), CD44, and SRY-box transcription factor 2, inhibited cell migration, invasion, and tumorigenesis and decreased the number of tumor spheroids and CD133⁺ cell population. Furthermore, we found that HN1L could bind to forkhead box P2 (FOXP2) and positively regulated transforming growth factor-β (TGF-β) expression via upregulation of FOXP2. In addition, the overexpression of TGF-β in HN1L-knockdown PCA cells increased the number of tumor spheroids and CD133⁺ cell population, as well as enhanced cell migration and invasion. Collectively, this study demonstrates that HN1L promotes stem cell-like properties and cancer progression by targeting FOXP2 through TGF-β signaling pathway in PCA.

中文翻译：

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HN1L 通过靶向前列腺癌中的 FOXP2 来调节 TGF-β 信号通路，从而促进干细胞样特性


血液学和神经学表达失调的 1-like (HN1L) 与不同癌症的致癌作用有关，包括肝细胞癌和乳腺癌。然而，HN1L 在前列腺癌 (PCA) 进展中的作用仍不清楚。因此，我们旨在研究 HN1L 在 PCA 干性和进展中的作用。通过定量逆转录聚合酶链反应 (qRT-PCR)、蛋白质印迹分析和/或免疫组织化学 (IHC) 测定 PCA 组织和细胞中 HN1L 的表达。使用磁性荧光细胞分选技术从 PCA 细胞中分选 CD133 ⁺细胞，并将其视为癌症干细胞 (CSC)。进行球体形成测定、transwell测定和动物实验分别评估细胞干性、迁移、侵袭和体内肿瘤发生。结果表明，与正常组织和细胞相比，PCA组织和细胞中HN1L的表达较高，CD133 ⁺细胞中的HN1L表达高于CD133 ^-细胞。 HN1L 敲低显着降低了 CSC 标志物的表达水平，包括 OCT4（POU 5 类同源盒 1）、CD44 和 SRY-box 转录因子 2，抑制细胞迁移、侵袭和肿瘤发生，并减少肿瘤球体和 CD133 ⁺细胞群的数量。此外，我们发现HN1L可以与叉头框P2（FOXP2）结合，并通过上调FOXP2来正向调节转化生长因子-β（TGF-β）的表达。此外，HN1L敲低PCA细胞中TGF-β的过度表达增加了肿瘤球体和CD133 ⁺细胞群的数量，并增强了细胞迁移和侵袭。 总的来说，这项研究表明，HN1L 通过 PCA 中的 TGF-β 信号通路靶向 FOXP2，从而促进干细胞样特性和癌症进展。