CELLULAR SIGNALLING
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2025
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IF 3.7
Qingqing Chen,Ling Ouyang
Recent findings have indicated that the F-box E3 ubiquitin ligase, F-box only protein 11 (FBXO11), may serve a tumor-suppressing role in certain types of cancers. However, its specific function in ovarian cancer (OC) remains to be elucidated. This study revealed that FBXO11 expression is reduced in OC tissues compared to normal tissues. To assess the role of FBXO11 in OC cells, we established stable human OC cell lines with tetracycline-inducible (Tet-on) expression of FBXO11 CDS or shRNA. FBXO11 inhibited OC cell proliferation, colony formation, migration, invasion, and cell cycle transition from G0/G1 to S phase in vitro . Moreover, FBXO11 suppressed xenograft tumor growth in mice in vivo . Concurrently, FBXO11 reduced the volume of ascites and the number of metastatic tumor nodules in the peritoneal metastasis model. Mechanistically, FBXO11 promoted kinesin family member 2C (KIF2C) to undergo K48-linked ubiquitination and proteasomal degradation, and KIF2C knockdown reversed the tumor-promoting function of FBXO11 downregulation. Additionally, we demonstrated that FBXO11 is a transcriptional target of zinc-finger protein 217 (ZNF217), a known transcriptional repressor that has been implicated in the promotion of OC progression and the prediction of poor prognosis. In summary, FBXO11 functions as a tumor suppressor in OC through ubiquitin-proteasomal degradation of KIF2C; and the low expression level of FBXO11 in OC may be attributed to its transcriptional inhibition by transcription factor ZNF217. These findings provided new insights into understanding the molecular mechanism of OC progression.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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DOI
PubMed
高影响因子
Genes & Diseases
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2021
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IF 7.103
Xiaofeng Zuo,Peixin Meng,Yuxin Bao,Chuntao Tao,Yitao Wang,Xianjun Liu,Youquan Bu,Jiang Zhu
Nasopharyngeal carcinoma (NPC) is a common malignant carcinoma of the head and neck, and the biological mechanisms underlying the pathogenesis of NPC remain not fully understood. In the present study, we systematically analyzed four independent NPC transcriptomic datasets and focused on identifying the critical molecular networks and novel key hub genes implicated in NPC. We found totally 170 common overlapping differentially expressed genes (DEGs) in the four NPC datasets. GO and KEGG pathway analysis revealed that cell cycle dysregulation is a critical event in NPC. Protein–protein interaction (PPI) network analysis identified a 15 hub-gene core network with overexpressed kinesin family member 2C (KIF2C) as a central regulator. Loss-of-function study demonstrated that knockdown of KIF2C significantly inhibited cell growth and cell motility, and delayed cell cycle progression, accompanied with dramatic mitotic defects in spindle formation in NPC cells. RNA-seq analysis revealed that KIF2C knockdown led to deregulation of various downstream genes. KIF2C could also regulate the AKT/mTOR pathways, and enhance paclitaxel sensitivity in NPC cells. Taken together, our results suggest that cell cycle dysregulation is a critical event during NPC pathogenesis and KIF2C is a novel key mitotic hub gene with therapeutic potential in NPC.
研究领域:
肿瘤学
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分子生物学
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基因组学
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DOI
PubMed
高影响因子
Open Medicine
·
2023
·Vol. 18
·期 1
·
IF 2.1
Haibin Li,Chunyan Zhang,Qiang Liu
Adverse cardiovascular events are associated with vascular calcification (VC) process, where vascular smooth muscle cells (VSMCs) differentiate into osteoblastic phenotype and deposit hydroxyapatite crystals. Microtubule-associated protein kinesin family member 2C (KIF2C) expression is decreased obviously in VSMC during calcification induction. Accordingly, we investigate the role and potential mechanism of KIF2C on VSMC calcification. The effects of β-glycerophosphate (β-GP)/KIF2C/lumican (LUM) on calcification, calcium content, alkaline phosphatase (ALP) activity, calcification-related markers, Tubulin, the ratio of polymerized (Po) to free (Fr) tubulin, as well as levels of LUM, apolipoprotein B (APOB), and KIF2C were assessed by Alizarin red S staining, calcium assay kit, ALP assay kit, Western blot, immunofluorescence, and quantitative real-time PCR. The interplay between LUM and APOB was estimated using co-immunoprecipitation and immunofluorescence. As a result, β-GP promoted calcification of human VMSCs (HVMSCs) and repressed KIF2C expression. KIF2C overexpression reversed the effect of β-GP on HVSMCs. LUM silencing attenuated β-GP-induced promotion on HVSMC calcification and increased KIF2C expression by interacting with APOB. Collectively, LUM silencing can alleviate β-GP-induced VSMC calcification through mitigating the repression of APOB on KIF2C expression.
研究领域:
心血管疾病
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细胞生物学
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分子生物学
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DOI
PubMed
高影响因子
American Journal of Cancer Research
·
2024
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IF 3.6
Haiyue Zhu,Yuxin Bao,Xuanqi Dou,Xiaofeng Zuo,Junhong Ye,Haiyu Ma,Youquan Bu,Yitao Wang,Jiang Zhu
Head and neck squamous cell carcinoma (HNSCC) is a significant cause of mortality, while the underlying mechanism remains unclear. Our studies have revealed that KIF2C plays a crucial role in tumor proliferation and metastasis in HNSCC. The results demonstrate that KIF2C is highly expressed at both the mRNA and protein levels and is closely associated with lymph node metastasis. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicate that the differentially expressed genes are enriched in processes or pathways related to cell adhesion and cell mitosis in HNSCC. Moreover, the established protein-protein interaction network identifies KIF2C as a potential hub gene in HNSCC. Knockdown of KIF2C has been demonstrated to significantly reduce cell migration and invasion ability, leading to cell cycle arrest, a high proportion of abnormal cell apoptosis, and cell chromosome division mismatches in the HNSCC cell line. Downstream genes such as PDGFA, EGFR, TP63, SNAI2, KRT5, and KRT14 were found to be down-regulated, and multiple critical pathways, including mTOR, ERK, and PI3K-AKT pathways, were inactivated as a result of KIF2C knockdown. These findings provide strong evidence for the crucial role of KIF2C in HNSCC and suggest that targeting KIF2C may be a promising therapeutic strategy for this disease. Knockdown of KIF2C has been shown to significantly inhibit tumor proliferation in nude mice, demonstrating the potential therapeutic role of KIF2C in HNSCC treatment.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
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癌症研究
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DOI
PubMed
高影响因子
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