HN1L promotes stem cell‐like properties by regulating TGF‐β signaling pathway through targeting FOXP2 in prostate cancer

Abstract

Dysregulated 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 qRT-PCR, western blotting 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, CD44 and SOX2, 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 FOXP2 and positively regulated TGF-β expression via upregulation of FOXP2. In addition, 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.