Background: Research has elucidated that homeobox B9 (HOXB9), an important transcriptional activator, plays a pivotal role in promoting the invasion and metastasis of hepatocellular carcinoma (HCC) cells. However, the mechanism by which HOXB9 promotes the invasion and metastasis of HCC cells is incompletely understood and needs further exploration.
Methods: HOXB9 and snail family transcriptional repressor 2 (SNAI2) expression were analyzed using qRT-PCR and western blotting. The invasion and metastasis of hepatocellular carcinoma (HCC) cells were investigated using in vitro and in vivo assays. The H3K27me3 enrichment and HOXB9 interaction with microRNA 203a (MIR203A) or SNAI2 were detected using ChIP-qPCR. Transcriptional activities of SNAI2 and MIR203A promoter were detected using dual-luciferase reporter assays. Co-IP and GST pull-down assays were performed to confirm the binding between HOXB9 and EZH2.
Results: HOXB9 and SNAI2 were highly expressed in HCC tissues and their expression was positively intercorrelated and associated with poor prognosis in patients with HCC. In vitro and in vivo experiments confirmed that HOXB9 can upregulate the expression of SNAI2 to promote the invasion and metastasis of HCC cells. Furthermore, HOXB9 elevated SNAI2 expression by inhibiting MIR203A expression, a tumor suppressor gene, in HCC cells. Mechanistically, HOXB9 recruited enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) through interaction with its WD-binding domain, which increased EZH2-mediated histone H3 lysine 27 trimethylation (H3K27me3) at the MIR203A promoter region, in turn repressing the transcriptional activity and expression of MIR203A and consequently increasing the SNAI2 level in HCC cells. Finally, empirical evidence from in vitro and in vivo studies confirmed that mitigation of the HOXB9-mediated enhancement of epigenetic silencing of MIR203A inhibited SNAI2 expression, impeding the invasion and metastasis of HCC cells.
Conclusions: Our study reveals a novel mechanism by which HOXB9 promotes the invasion and metastasis of HCC cells and expands the understanding of the function of HOXB9 in tumor progression and provides a novel therapeutic strategy for curtailing HCC invasion and metastasis.
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http://dx.doi.org/10.1186/s12967-024-05690-x | DOI Listing |
Front Oncol
December 2024
Organ Transplantation Clinical Medical Center of Xiamen University, Department of Organ Transplantation, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China.
A 13-year-old boy was admitted to Xiang'an Hospital of Xiamen University due to HBV-related liver cancer. Intrahepatic metastasis was considered to occur by CT scan. A gastroscope revealed esophagogastric variceal bleeding, and later, the patient underwent a successful liver transplantation.
View Article and Find Full Text PDFInnate Immun
December 2024
Department of Clinical Pathology, Faculty of Medicine, Ain-Shams University, Cairo, Egypt.
Background: Globally, colorectal cancer (CRC) is among the most prevalent malignant tumors. It is characterized by unlimited proliferation, invasion, and metastasis. MicroRNA-126 (miR-126) has been shown in many studies to play a significant role in CRC, but data regarding its role in CRC Egyptian patients are limited.
View Article and Find Full Text PDFBiotechnol J
December 2024
Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.
With a high mortality rate, colon cancer (CC) is the third most common malignant tumor worldwide. The primary causes are thought to be the high invasiveness and migration of CC cells. The functions of Golgi phosphoprotein 3 (GOLPH3), stress-induced phosphoprotein 1 (STIP1), and the signal transducer and activator of transcription 3 (STAT3) signaling pathway in the invasion and migration of CC cells were examined in this study.
View Article and Find Full Text PDFNat Cancer
December 2024
Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
The cerebrospinal fluid (CSF) border accommodates diverse immune cells that permit peripheral cell immunosurveillance. However, the intricate interactions between CSF immune cells and infiltrating cancer cells remain poorly understood. Here we use fate mapping, longitudinal time-lapse imaging and multiomics technologies to investigate the precise origin, cellular crosstalk and molecular landscape of macrophages that contribute to leptomeningeal metastasis (LM) progression.
View Article and Find Full Text PDFBMC Cancer
December 2024
Department of Cardiothoracic Surgery, Shenzhen Guangming District People's Hospital, Shenzhen, China.
Background: Long non-coding RNA 01116 (linc01116) has been shown to be dysregulated in many tumors, and is closely related to the prognosis. This meta-analysis aimed to examine the correlation between linc01116 expression and cancer prognosis.
Methods: Six electronic databases were searched, and eligible studies were screened based on the inclusion and exclusion criteria.
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