Cell Division最新文献

Background: Zinc finger protein 169 (ZNF169) plays a key role in cancer development. However, the specific role of ZNF169 in the tumorigenesis of thyroid carcinoma (THCA) remains poorly understood.

Methods: The expression of ZNF169 was measured using immunohistochemistry, RT-qPCR, and western blot. Cell proliferation was detected using CCK-8 assay and cell colony formation assays, while cell migration was determined by Transwell assay. Flow cytometry was used to detect cell apoptosis and cell cycle distribution. The interaction of ZNF169 and its downstream gene was studied using luciferase assay and CHIP-PCR. Recovery assay in cells and animals were also performed to demonstrate the mechanism.

Results: ZNF169 was highly expressed in THCA tissues and cells lines compared with matched adjacent non-cancerous thyroid tissues or normal thyroid epithelial cell. Moreover, thyroid cancer cell proliferation and migration were suppressed following ZNF169 knockdown, while were potentiated by ZNF169 overexpression. ZNF169 also regulate THCA cell apoptosis and cell cycle progression. Mechanically, ZNF169 enhanced the transcription activity and expression of F-box/WD repeat-containing protein 10 (FBXW10) via the binding to its promoter. There was a positive correlation between ZNF169 and FBXW10 in THCA patients. In addition, knockdown of FBXW10 suppressed the proliferation of THCA cells. Recovery assays in vitro and in vivo demonstrated that FBXW10 knockdown reversed the effects of ZNF169 overexpression on THCA cell proliferation and tumor growth.

Conclusions: In summary, ZNF169 promotes THCA progression via upregulation of FBXW10, which may provide a novel theoretical basis for the development of clinical therapies for THCA.

Objective: This study aimed to investigate the regulatory effects of long non-coding RNA-ANRIL on CDKN2A in the cell cycle of Kasumi-1 cells and elucidate the underlying molecular mechanisms.

Methods: ANRIL and CDKN2A expression levels were quantified using RT-qPCR in peripheral blood samples from acute myeloid leukemia (AML) patients. CDKN2A knockdown efficiency was validated via RT-qPCR, and cell cycle distribution was analyzed using flow cytometry. Cell proliferation assays were conducted with CCK-8 following palbociclib treatment and CDKN2A downregulation. RNA immunoprecipitation (RIP) identified potential ANRIL-associated targets, while western blotting assessed the expression levels of GSK3β/β-catenin/cyclin D1 signaling components and related proteins.

Results: ANRIL and CDKN2A were markedly overexpressed in AML patient samples. Knockdown of ANRIL and CDKN2A led to G1 phase arrest accompanied by reduced CDK2/4/6 and cyclin D1 protein levels, while ANRIL upregulation induced the opposite effect. Palbociclib treatment for 24 h and 48 h elevated the G1 phase cell population and suppressed CDK2/4/6 and cyclin D1 protein expression, demonstrating its ability to counteract ANRIL-driven cell cycle progression. Downregulation of ANRIL and CDKN2A also suppressed the GSK3β/β-catenin signaling pathway, reducing cyclin D1 expression, whereas ANRIL upregulation reactivated this axis. Co-transfection experiments showed that simultaneous cyclin D1 suppression and ANRIL overexpression attenuated ANRIL's stimulatory effects on cell cycle progression. RIP analysis confirmed a physical interaction between ANRIL and CDKN2A. Furthermore, CDKN2A downregulation inhibited cell proliferation and reversed GSK3β/β-catenin/cyclin D1 pathway activation mediated by ANRIL upregulation.

Conclusion: ANRIL facilitates Kasumi-1 cell survival by modulating CDKN2A to activate the GSK3β/β-catenin/cyclin D1 signaling pathway.

Background: Dysregulation of SF3A3 has been related to the development of many cancers. Here, we investigated the functional role of SF3A3 in hepatocellular carcinoma (HCC).

Methods: SF3A3 expression in HCC tissues and cell lines was examined using RT-qPCR. Changes in malignant behavior of HCC cells after downregulation of SF3A3 were assessed by EdU, colony formation, flow cytometry, wound healing, and Transwell invasion assays. Multiple datasets were combined to identify the upstream modifiers of SF3A3. The binding relationship between STIL and FOXM1 was explored by co-IP assay, and the effect of STIL and FOXM1 on the binding of FOXM1 at the SF3A3 promoter was detected by ChIP-qPCR assay. A xenograft tumor model was established to explore the changes of tumors in vivo, and the expression of Ki67, GPC3, and p53 in tumor tissues was detected by immunohistochemistry.

Results: SF3A3 and STIL were overexpressed in HCC tissues and cells, and downregulation of SF3A3 or STIL inhibited the malignant behavior of HCC cells by promoting the expression of p53. An interaction between STIL and FOXM1 regulated the SF3A3 expression in HCC cells. Knockdown of FOXM1 further enhanced the anti-tumor effects of STIL loss on HCC cells in vitro and in vivo, whereas SF3A3 overexpression overturned the impact of STIL loss on HCC cells in vitro and in vivo.

Conclusions: Our findings indicate that STIL/FOXM1 expedites HCC development by activating SF3A3, which highlights the importance of SF3A3 as a promising prognostic marker and therapeutic target for HCC.

Background: Mitosis and cytokinesis are regulated by reversible phosphorylation events controlled by kinases and phosphatases. Drosophila Polo kinase, like its human ortholog PLK1, plays several roles in this process. Multiple mechanisms contribute to regulate Polo/PLK1 activity, localization and interactions. We previously showed that the microtubule-associated protein Map205 interacts with Polo during interphase and cytokinesis, inhibiting and sequestering Polo on microtubules. During mitosis, phosphorylation of Map205 at a Cyclin-Dependent Kinase site allows Polo to dissociate from Map205, when Polo must fulfill its mitotic functions. How the Polo/Map205 interaction is restored during mitotic exit remained unknown.

Results: Here we show that PP2A-Tws/B55 is required to dephosphorylate Map205, and enables the Map205-dependent localization of Polo to microtubules during cytokinesis. In addition, we show that PP2A-Tws is required for spindle function during cytokinesis, consistent with the essential role of Polo in this process.

Conclusions: These findings complement previous studies to provide an understanding of the full cycle of Polo regulation by Map205, kinases and phosphatases. Our findings have implications for the wider network of cell cycle regulatory circuitry.

Background: Abnormal expression of six-transmembrane epithelial antigen of prostate 4 (STEAP4) has been implicated in the carcinogenesis of hepatocellular carcinoma (HCC). However, the biological role and regulatory mechanisms of STEAP4 in HCC remain unclear.

Methods and results: Here, we analyzed STEAP4 expression levels and differentially expressed genes (DEGs) between STEAP4 high- and low-expression groups using multiple databases. Proliferation assays, 5-ethynyl-2'-deoxyuridine (EdU) assays, propidium iodide (PI) flow cytometry, and colony formation assays were conducted to assess the effects of STEAP4 on HCC cell proliferation, cell cycle progression, and clonogenic capacity. STEAP4 was downregulated in HCC tumor tissues, with lower expression associated with poorer overall survival (OS) and disease-free survival (DFS) in patients. Functional network analysis suggested that STEAP4 regulates cell cycle signaling, with tumor sections showing a negative correlation between STEAP4 and cell cycle proteins. Overexpression of STEAP4, combined with non-cytotoxic copper exposure in the HepG2 cell line, reduced proliferation and clonogenicity, induced cell cycle arrest, and downregulated the mRNA and protein levels of cell cycle-regulating genes. A predictive model based on STEAP4 and cell cycle gene demonstrated prognostic value in HCC patients.

Conclusions: Our results lay a foundation for further study of the cell cycle regulatory role of STEAP4 with Cu²⁺ reductase activity in HCC, indicating that STEAP4 may be a promising therapeutic target for HCC.

Background: Pre-eclampsia (PE) is a pregnancy specific disease characterized by hypertension and proteinuria. The aim of this study was to investigate the effects of Zinc finger E-box binding homologous box 2 (ZEB2) on PE mice and on placental trophoblast cells, as well as to elucidate its role in Wnt/β-Catenin pathway.

Methods: The PE mice models were established through L-NAME administration. RT-qPCR and western blot assay were used to detect the expression of ZEB2 in human serum, placental tissues, HTR8/Sveno cells, and mice models. Edu assay, flow cytometry, and Transwell analysis were applied for determining HTR8/Sveno cells proliferation, apoptosis, migration, and invasion ability, respectively. The expression levels of related proteins in the Wnt/β-Catenin pathway were detected by western blot analysis. The systolic blood pressure (SBP) of mice was analyzed by the noninvasive tail cuff method. Proteinuria was detected using CBB kits and TUNEL method was used to measure apoptosis of placental tissue cells in PE mice.

Results: The significant increase SBP and urinary protein in L-NAME treated mice indicated the successful construction of the PE mice model. We found that ZEB2 was down-regulated in the serum and placental tissues of PE patients. Further in vitro experiments showed that ZEB2-plasmid enhanced cell proliferation, migration, and invasion, as well as reduced cell apoptosis, compared with the control-plasmid group. In addition, up-regulation of ZEB2 promoted the protein level of Bcl-2 in HTR-8/SVneo cells and inhibited Bax expression. We also found that ZEB2-plasmid activated Wnt/β-Catenin signaling pathway, as confirmed by enhanced Wnt3a, β-Catenin, p-GSK3β, C-Myc, and Cyclin D1 expression. Importantly, the Wnt/β-Catenin signaling inhibitor (XAV939) partially reversed the effects of ZEB2-plasmid on HTR-8/SVneo cells. We also observed similar findings in in vivo mice models as in vitro cell experiments.

Conclusion: ZEB2 was involved in the pathological and physiological processes of PE through Wnt/β-Catenin pathway, which may provide a useful perspective for exploring new therapies for PE.

Cervical carcinoma poses a significant health threat, with traditional treatments proving inadequate in advanced stages. Curcumin, a bioactive compound derived from turmeric, exhibits notable anti-inflammatory, antioxidant, and antineoplastic properties, potentially modulating autophagy, and metastasis in cancer cells. This study examines curcumin's impact on autophagy and metastasis in cervical carcinoma, focusing on its interaction with autophagy-related gene 3 (ATG3). SiHa and HeLa cervical carcinoma cell lines were treated with curcumin, ATG3 knockdown (shATG3), and their combination. Cell migration was evaluated via wound healing assays, while cell proliferation was evaluated with CCK-8 assays. LC3 expression was assessed using immunofluorescence and western blotting. Molecular docking simulations identified curcumin's binding interactions with key proteins. Curcumin and shATG3 significantly inhibited both cell migration and proliferation, with a synergistic effect observed when combined. LC3 expression was enhanced, indicating increased autophagy. Docking studies revealed curcumin's potential binding to MMP2, MMP9, TGF-β, ATG3, LC3, and p62, suggesting modulation of these pathways. The combination of curcumin and ATG3 knockdown significantly inhibited cervical carcinoma cell migration and proliferation, while also enhancing autophagy, supporting the potential of curcumin as a therapeutic agent for cervical carcinoma. Further clinical research is needed to validate these findings.

Purpose: Cervical cancer (CC), a significant global health threat, necessitates comprehensive understanding for improved therapeutic interventions. Many research indicates that dysregulation of the Hippo-YAP1 pathway leads to uncontrolled proliferation and invasion of tumor cells, promoting the progression of various cancers. This article aims to elucidate the role of RNF6 in CC and its regulation of the Hippo-YAP1 signaling pathway.

Methods: The public tumor dataset analyses, immunohistochemistry, and western blotting were used to explore the expression of RNF6 in CC. Gain- and loss-of-function assays were conducted to elucidate the role of RNF6 in the proliferation and invasion of CC cells. Transcriptome sequencing was used to explore RNF6's role in cervical cancer, with validation of its regulation of the Hippo-YAP1 pathway through western blotting and RT-qPCR. Co-transfection of YAP overexpression plasmids into RNF6-silenced CC cells were preformed to confirm YAP1's pivotal role in RNF6-mediated CC progression. Animal experiments were preformed to further validate RNF6 interference's inhibitory effect on CC proliferation in vivo.

Results: Clinical samples and bioinformatics analysis revealed high expression of RNF6 in CC, and closely associated with advanced FIGO (International Federation of Gynecology and Obstetrics) stage, larger tumor size, and poor prognosis. Cellular functional experiments demonstrate that RNF6 promotes the proliferation, invasion, and migration of CC cells, while knockdown of RNF6 yields the opposite effect. Transcriptome sequencing further reveals that RNF6 may promote CC progression through the Hippo-YAP signaling pathway. Western blotting and RT-qPCR further unveil that RNF6 enhances the upregulation of YAP1 protein levels, thereby activating downstream oncogenes CTGF and CYR61 transcription. Additionally, exogenous overexpression of YAP1 reverses the inhibitory effect of RNF6 silencing on CC proliferation and invasion. Furthermore, RNF6 interference significantly attenuates tumor growth in vivo experiments.

Conclusion: Our research reveals that RNF6 is highly expressed in CC, driving malignant progression by upregulating YAP1 protein expression and enhancing the transcription of downstream target genes CTGF and CYR61, offering potential therapeutic targets for CC treatment.

Objective: Hepatocellular carcinoma (HCC) is fatal and poses great challenges to early diagnosis and effective treatment. This paper sought to expound the function of Zinc finger and SCAN domain-containing protein 16 (ZSCAN16) and TBC1 domain family member 31 (TBC1D31) in HCC progression.

Methods: ZSCAN16 and TBC1D31 levels were detected by RT-qPCR, Western blot, and immunohistochemistry. The transcriptional regulation of TBC1D31 by ZSCAN16 was demonstrated by ChIP-qPCR and dual-luciferase assay. Colony formation assay, migration and invasion assays, TUNEL staining, CCK-8 assay, flow cytometry, and western blot analysis were adopted to evaluate the biological activity of HCC cells. The role of the ZSCAN16/TBC1D31 axis in HCC was demonstrated by lentiviral gene intervention combined with functional rescue experiments. Hep3B cells were used to establish a nude mouse xenograft tumor model to study the role of the ZSCAN16/TBC1D31 axis in vivo.

Results: ZSCAN16 and TBC1D31 were highly expressed in HCC. Downregulation of ZSCAN16 repressed the proliferation, migration, and invasion of HCC cells while promoting apoptosis, as well as curbing tumor growth in vivo. Mechanistic studies showed that ZSCAN16 mediated the transcriptional activation of TBC1D31, which in turn led to tumor development. TBC1D31 overexpression reversed the inhibitory effect of ZSCAN16 knockdown on the malignant behavior and tumor growth of HCC cells and accelerated tumor development.

Conclusion: ZSCAN16 mediates transcriptional activation of TBC1D31 and promotes HCC progression.

Glioblastomas (GBM) are most common types of primary brain tumors and miRNAs play an important role in pathogenesis of glioblastomas. Here, we reported a new miRNA, miR-3154, which regulates glioblastoma proliferation and metastasis. miR-3154 was elevated in glioblastoma tissue and cell lines, and its elevation was associated with grade of glioblastomas. Knockdown of miR-3154 in cell lines weakened ability of proliferation and colony formation, and caused cell cycle arrested and higher percentage of apoptosis. Knockdown of miR-3154 also impaired ability of migration and invasion in glioblastoma cells. In mechanism, miR-3154 bound directly to Tumor Protein P53 Inducible Nuclear Protein 1 (TP53INP1), down-regulating TP53INP1 expression at both mRNA and protein level. Silence of TP53INP1 reversed the effect of miR-3154 knockdown on proliferation and metastasis of glioblastoma cells. These findings show that miR-3154 promotes glioblastoma proliferation and metastasis via targeting TP53INP1.