Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger pr...Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZN展开更多
The liver is the most common site of metastases in patients with colorectal cancer.Colorectal liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver microenvironment.Th...The liver is the most common site of metastases in patients with colorectal cancer.Colorectal liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver microenvironment.The aberrant activation of Wingless/It(Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium,but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymalepithelial transition interactions.In liver microenvironment,metastatic cells can also survive and adapt through dormancy,which makes them less susceptible to pro-apoptotic signals and therapies.Treatment of CRLMs is challenging due to its variability and heterogeneity.Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been recognized in chemoresistance.At the state of art,there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie.In this review,current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered.In addition,an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.展开更多
基金supported by the Science-Technology Foundation for Middle-aged and Young Scientists of Wannan Medical College(No.WK2021F19)the 2023 Wannan Medical College Research Fund(No.WK2023ZZD18).
文摘Objective:Uterine corpus endometrial carcinoma(UCEC),a kind of gynecologic malignancy,poses a significant risk to women’s health.The precise mechanism underlying the development of UCEC remains elusive.Zinc finger protein 554(ZNF554),a member of the Krüppel-associated box domain zinc finger protein superfamily,was reported to be dysregulated in various illnesses,including malignant tumors.This study aimed to examine the involvement of ZNF554 in the development of UCEC.Methods:The expression of ZNF554 in UCEC tissues and cell lines were examined by qRT-PCR and Western blot assay.Cells with stably overexpressed or knocked-down ZNF554 were established through lentivirus infection.CCK-8,wound healing,and Transwell invasion assays were employed to assess cell proliferation,migration,and invasion.Propidium iodide(PI)staining combined with fluorescence-activated cell sorting(FACS)flow cytometer was utilized to detect cell cycle distribution.qRT-PCR and Western blotting were conducted to examine relative mRNA and protein levels.Chromatin immunoprecipitation assay and luciferase reporter assay were used to explore the regulatory role of ZNF554 in RNA binding motif 5(RBM5).Results:The expression of ZNF554 was found to be reduced in both UCEC samples and cell lines.Decreased expression of ZNF554 was associated with higher tumor stage,decreased overall survival,and reduced disease-free survival in UCEC.ZNF554 overexpression suppressed cell proliferation,migration,and invasion,while also inducing cell cycle arrest.In contrast,a decrease in ZNF554 expression resulted in the opposite effect.Mechanistically,ZNF554 transcriptionally regulated RBM5,leading to the deactivation of the Wingless(WNT)/β-catenin signaling pathway.Moreover,the findings from rescue studies demonstrated that the inhibition of RBM5 negated the impact of ZNF554 overexpression onβ-catenin and p-glycogen synthase kinase-3β(p-GSK-3β).Similarly,the deliberate activation of RBM5 reduced the increase inβ-catenin and p-GSK-3βcaused by the suppression of ZN
文摘The liver is the most common site of metastases in patients with colorectal cancer.Colorectal liver metastases(CRLMs)are the result of molecular mechanisms that involve different cells of the liver microenvironment.The aberrant activation of Wingless/It(Wnt)/β-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium,but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymalepithelial transition interactions.In liver microenvironment,metastatic cells can also survive and adapt through dormancy,which makes them less susceptible to pro-apoptotic signals and therapies.Treatment of CRLMs is challenging due to its variability and heterogeneity.Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/β-catenin pathway has been recognized in chemoresistance.At the state of art,there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie.In this review,current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered.In addition,an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.
