The forkhead box transcription factor A2 (FOXA2) is a member of the hepatocyte nuclear factor family and plays an important role in liver development and metabolic homeostasis, but its role in the metastasis of hepatocellular carcinoma (HCC) has not been evaluated. In this study, we found that the expression of FOXA2 was decreased in 68.1% (49/72) of human HCC tissues compared with their paired non-cancerous adjacent tissues. Clinicopathological analysis revealed that reduced FOXA2 expression was correlated with aggressive characteristics (venous invasion, poor differentiation, high tumor node metastasis grade). FOXA2 level was even lower in portal vein tumor thrombus compared with primary tumor tissues and correlated with epithelial-mesenchymal transition in HCC cells. Overexpression of FOXA2 inhibited migration and invasion of Focus cells, whereas knockdown of FOXA2 in HepG2 showed the opposite effect. Moreover, upregulation of FOXA2 suppressed HCC metastasis to bone, brain and lung in two distinct mouse models. Finally, we proved that FOXA2 repressed the transcription of matrix metalloproteinase (MMP)-9 and exerted its antimetastasis effect partially through downregulation of MMP-9. In conclusion, our findings indicate that FOXA2 plays a critical role in HCC metastasis and may serve as a novel therapeutic target for HCC.
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http://dx.doi.org/10.1093/carcin/bgu180 | DOI Listing |
J Cancer
January 2025
Department of Oral and Maxillofacial Surgery, School of Stomatology, Hebei Medical University, Hebei Technology Innovation Center of Oral Health, Key Laboratory of Stomatology and Clinical Research Centre for Oral Diseases, Hebei Province, Shijiazhuang, 050017, China.
HOXD13, a member of the homeobox gene family, plays a critical role in developmental processes and has been implicated in various malignancies, including pancreatic cancer and glioma. However, its role in oral squamous cell carcinoma (OSCC) remains poorly understood. This study aimed to elucidate the potential of HOXD13 as a diagnostic biomarker and therapeutic target for OSCC.
View Article and Find Full Text PDFExp Cell Res
December 2024
Biology Teaching and Research Office, Tianjin Vocational Institute, Tianjin, China.
Hypoxia-caused spermatogenesis impairment may contribute to male infertility. FOXA2 has been found to be abundant in spermatogonial stem cells and critical for spermatogenesis. Here we aimed to explore the roles of FOXA2 in regulating spermatogonial cells against hypoxia stimulation.
View Article and Find Full Text PDFCells
December 2024
Vancouver Prostate Centre, Department of Urological Sciences, University of British Columbia, Vancouver, BC V6H 3Z6, Canada.
Neuroendocrine prostate cancer (NEPC), an aggressive and lethal subtype of prostate cancer (PCa), often arises as a resistance mechanism in patients undergoing hormone therapy for prostate adenocarcinoma. NEPC is associated with a significantly poor prognosis and shorter overall survival compared to conventional prostate adenocarcinoma due to its aggressive nature and limited response to standard of care therapies. This transdifferentiation, or lineage reprogramming, to NEPC is characterised by the loss of androgen receptor (AR) and prostate-specific antigen (PSA) expression, and the upregulation of neuroendocrine (NE) biomarkers such as neuron-specific enolase (NSE), chromogranin-A (CHGA), synaptophysin (SYP), and neural cell adhesion molecule 1 (NCAM1/CD56), which are critical for NEPC diagnosis.
View Article and Find Full Text PDFA significant number of castration-resistant prostate cancer (CRPC) evolve into a neuroendocrine (NE) subtype termed NEPC, leading to resistance to androgen receptor (AR) pathway inhibitors and poor clinical outcomes. Through Hi-C analyses of a panel of patient-derived xenograft tumors, here we report drastically different 3D chromatin architectures between NEPC and CRPC samples. Such chromatin re-organization was faithfully recapitulated in vitro on isogenic cells undergoing NE transformation (NET).
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon, 34141, Republic of Korea.
Cellular differentiation is controlled by intricate layers of gene regulation, involving the modulation of gene expression by various transcriptional regulators. Due to the complexity of gene regulation, identifying master regulators across the differentiation trajectory has been a longstanding challenge. To tackle this problem, a computational framework, single-cell Boolean network inference and control (BENEIN), is presented.
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