HN1L promotes stem cell‐like properties by regulating TGF‐β signaling pathway through targeting FOXP2 in prostate cancer
- 14 September 2021
- journal article
- research article
- Published by Wiley in Cell Biology International
- Vol. 46 (1), 83-95
- https://doi.org/10.1002/cbin.11701
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.This publication has 33 references indexed in Scilit:
- Downregulation of FOXP2 promoter human hepatocellular carcinoma cell invasionTumor Biology, 2015
- The Forkhead Transcription Factor FOXP2 Is Required for Regulation of p21WAF1/CIP1 in 143B Osteosarcoma Cell Growth ArrestPLOS ONE, 2015
- MSC-Regulated MicroRNAs Converge on the Transcription Factor FOXP2 and Promote Breast Cancer MetastasisCell Stem Cell, 2014
- HN1 Negatively Influences the β‐Catenin/E‐Cadherin Interaction, and Contributes to Migration in Prostate CellsJournal of Cellular Biochemistry, 2014
- Mechanisms Governing Metastatic Dormancy and ReactivationCell, 2013
- Defining the mode of tumour growth by clonal analysisNature, 2012
- Androgen regulated HN1 leads proteosomal degradation of androgen receptor (AR) and negatively influences AR mediated transactivation in prostate cellsMolecular and Cellular Endocrinology, 2012
- Ubiquitously Expressed Hematological and Neurological Expressed 1 Downregulates Akt-Mediated GSK3β Signaling, and Its Knockdown Results in Deregulated G2/M Transition in Prostate CellsDNA and Cell Biology, 2011
- Radical Prostatectomy versus Watchful Waiting in Early Prostate CancerThe New England Journal of Medicine, 2011
- Cloning, expression and subcellular localization of HN1 and HN1L genes, as well as characterization of their orthologs, defining an evolutionarily conserved gene familyGene, 2004