Browsing by Subject "Ubiquitination"

Now showing 1 - 3 of 3
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    BPTF promotes glioma development through USP34-mediated de-ubiquitination of FOXC1
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2025) Pan, Yanling; Yuan, Feng; Lin, Zhiren; Li, Yijie
    Glioma is the most prevalent malignant tumor of the brain, and the study of the molecular mechanisms associated with its development has important clinical significance. Our previous study found that BPTF promotes the malignant phenotype of glioma and is significantly associated with poor prognosis; the downstream regulatory mechanisms are explored in this study. Western blot and immuno-histochemical staining were used to detect protein expression in cells or tissues. BPTF knockdown as well as FOXC1-overexpressing lentiviruses were used in combination for the construction of the U251 cell model, leading to functional rescue experiments. CCK8 assay, flow cytometry, scratch assay, and Transwell assay were used to detect cell proliferation, apoptosis, and migration, respectively. Finally, immuno-precipitation assays, combined with western blot (WB), were used to detect the interaction between proteins as well as the level of ubiquitination modification. The obtained results suggested that BPTF knockdown may inhibit the malignant behavior of glioma cells by downregulating FOXC1 expression. Moreover, FOXC1 expression was significantly higher in glioma tissues than in normal brain tissues and was significantly associated with higher tumor stage and worse patient prognosis. Finally, the mechanism of FOXC1 regulation by BPTF was found to result from the affected protein stability of FOXC1 through USP34-mediated de-ubiquitylation. In conclusion, the BPTF/FOXC1 axis was identified as a key promotor in glioma development and may be a potential target in the inhibition of glioma development.
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    Suppressing SMURF1 to preserve GSTM2: An approach to reducing gastric cancer aggressiveness in vitro and in vivo
    (2026) Jingwu Li; Yuanting Liu; Weiwei Zuo; Guoming Ma; Biología Celular e Histología
    Background. Smad Ubiquitination Regulatory Factor-1 (SMURF1) is implicated in promoting gastric cancer progression by enhancing cell proliferation, migration, and invasion. This study aims to elucidate how SMURF1 drives gastric cancer aggressiveness, with a focus on its interaction with Glutathione S-transferase mu 2 (GSTM2). Methods. Bioinformatics analysis identified dysregulated SMURF1 and GSTM2 expression in stomach adenocarcinoma (STAD). The relation between GSTM2 and SMURF1 was predicted using Unibrowser. Functional assays, including cell counting kit-8, wound healing, and Transwell invasion, were conducted on gastric cancer cells to explore the effects of GSTM2 and/or SMURF1. The ubiquitination level of GSTM2 was measured using western blot and immuno-precipitation. In vivo tumorigenicity was assessed in a xenograft mouse model, alongside analysis of tumor growth and molecular markers of epithelial-mesenchymal transition (EMT). Results. SMURF1 was highly expressed and the GSTM2 level was significantly downregulated in STAD. GSTM2 silencing activated the viability, migration, and invasion of gastric cancer cells, and these cell functions were inhibited by GSTM2 overexpression, which was reversed by SMURF1 overexpression. SMURF1 was predicted to be an E3 ubiquitin ligase for GSTM2. SMURF1 overexpression or Cyclohexanecarboxamide (CHX) addition suppressed GSTM2 levels in gastric cancer cells. Silencing of SMURF1 restrained GSTM2 ubiquitination. In vivo, GSTM2 overexpression suppressed tumor growth and EMT markers, such as Vimentin, while elevating E-cadherin, which was offset by SMURF1 upregulation. Conclusion. This study reveals a novel oncogenic axis, where SMURF1 promotes gastric cancer progression by targeting GSTM2 for degradation. Inhibiting SMURF1 stabilizes GSTM2, leading to reduced cell proliferation, migration, and invasion both in vitro and in vivo.
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    TRIM3 inhibits colorectal cancer cell migration and lipid droplet formation by promoting FABP4 degradation
    (Universidad de Murcia, Departamento de Biologia Celular e Histiologia, 2024) Zuo, Qi; Xu, Qimei; Li, Zhen; Luo, Dixian; Peng, Hanwu; Duan, Zhi
    This study is to investigate the regulation of TRIM3/FABP4 on colorectal cancer (CRC) cell migration and lipid metabolism. After transfection of HCT116, LoVo, or SW480 cells, the expression of FABP4, TRIM3, N-cadherin, Vimentin, E-cadherin, and lipid droplet (LD) formation-related genes was measured by qRT-PCR or western blot assays. Wound healing and Transwell assays were applied to detect CRC cell migration and invasion abilities. The levels of triglyceride (TG) and total cholesterol (TC) were measured and the formation of LDs was observed. Additionally, the relationship between FABP4 and TRIM3 was confirmed by Co-IP and ubiquitination assays. Furthermore, a liver metastasis model of CRC was established to explore the effect of FABP4 on CRC tumor metastasis in vivo. FABP4 was upregulated in CRC cells. Downregulation of FABP4 or upregulation of TRIM3 resulted in repressed cell migration and invasion, decreased TG and TC levels, and reduced numbers of LDs. In nude mice, knockdown of FABP4 reduced metastatic nodules in the liver. Mechanistically, TRIM3 combined FABP4 and decreased its protein expression by ubiquitination. Overexpressed FABP4 reversed the influence of TRIM3 upregulation on CRC cell migration and LD formation. In conclusion, underexpressed TRIM3 suppressed FABP4 ubiquitination and accelerated CRC cell migration and LD formation