Dataset Information

ZNF671 Inhibits the Proliferation and Metastasis of NSCLC via the Wnt/?-Catenin Pathway.

ABSTRACT: Background:Lung cancer is the most common cancer in the world and is the main cause of cancer-related death. Revealing the potential mechanism of malignant characteristics of lung cancer is urgent for treating this disease effectively. Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. The role of ZNF671 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of this study was to investigate the function and mechanism of ZNF671 in NSCLC. Methods:ZNF671 expression in NSCLC cells and tissues were detected by Real-Time PCR, Western blot and TCGA databases. Then, we evaluated the prognostic value of ZNF671 expression in NSCLC using the Kaplan-Meier plotter (KM plotter) and TCGA databases. Moreover, the function of ZNF671 in the proliferation and metastasis of lung cancer was investigated by MTT assay, colony formation assay, in vivo experiment, EdU assay, wound healing assay, transwell assay, and 3D culture assay. Luciferase reporter and subcellular fractionation assays were performed to determine the underlying mechanism of ZNF671-mediated proliferation and metastasis of NSCLC. Results:ZNF671 expression was significantly reduced in both NSCLC cell lines and clinical specimens compared to that in normal controls. The survival analysis results indicated that the downregulation of ZNF671 significantly correlates with poor prognosis and predicts a shorter overall survival and post-progression survival among NSCLC patients. Ectopic overexpression of ZNF671 dramatically restrains, whereas silencing ZNF671 enhanced, cell proliferation and metastasis of NSCLC. Mechanically, gene set enrichment analysis (GSEA) showed that the expression of ZNF671 was significantly correlated with Wnt/?-catenin signaling. Simultaneously, our results confirm that the overexpression of ZNF671 inhibits cell cycle progression and metastasis by weakening the Wnt/?-catenin pathway, and then downregulating the expression of downstream target genes CyclinD1 and MMP9. Conclusion:This study found that the overexpression of ZNF671 restrains the proliferation and metastasis of lung cancer through inhibiting Wnt/?-catenin signaling pathway. Furthermore, our current results provide important insights into ZNF671 as an excellent predictive biomarker for NSCLC, thus providing a novel perspective for the treatment of NSCLC.

SUBMITTER: Zhan W

PROVIDER: S-EPMC6986545 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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ZNF671 Inhibits the Proliferation and Metastasis of NSCLC via the Wnt/β-Catenin Pathway.

Zhan Wei W Li Yuzhe Y Liu Xuhui X Zheng Changlong C Fu Yongmei Y

Cancer management and research 20200124

<h4>Background</h4>Lung cancer is the most common cancer in the world and is the main cause of cancer-related death. Revealing the potential mechanism of malignant characteristics of lung cancer is urgent for treating this disease effectively. Zinc finger protein 671 (ZNF671) is a member of the largest transcription factor family in the human genome. The role of ZNF671 in non-small-cell lung cancer (NSCLC) remains unknown. The purpose of this study was to investigate the function and mechanism o ...[more]

PMID: 32158264

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Project description:Osteosarcoma (OS) is a rare type of tumor and mostly occurs in children and adolescents. Approximately 10‑25% of patients with OS have lung metastases, and lung damage caused by lung metastasis is the main cause of mortality. Therefore, studying the growth and metastasis of OS is key in reducing OS mortality and improving prognosis. The expression of long non‑coding RNA (lncRNA) cancer susceptibility 15 (CASC15) in OS patients or OS cell lines were quantified by reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). The expression of vimentin, E‑cadherin, N‑cadherin, and cyclin D were detected by RT‑qPCR and western blotting. Mice were injected with OS cell lines via the tail vein to observe tumor formation in the lung. CCK‑8 and EdU assays were utilized to evaluate cell proliferation. Both Ttranswell assay and cell scratch test detected cell migration. The results revealed that lncRNA‑CASC15 was highly expressed in clinical samples and OS cells. In vitro verification experiments revealed that CASC15 promoted the growth of OS cells. Rescue experiments demonstrated that CASC15 affected the cell cycle by activating the Wnt/β‑catenin pathway, thereby promoting cell proliferation. Furthermore, the transfection dose test indicated that lentiviruses expressing various doses of CASC15‑overexpression (oe‑CASC15) altered the proliferation and migration status of OS cells. CASC15 promoted OS cell metastasis both in vivo and in vitro. The overexpression of CASC15 revealed that the occurrence of metastasis was also related to the Wnt/β‑catenin pathway. The western blotting results revealed that CASC15 could lead to β‑catenin entering the nucleus via the Wnt pathway to promote the epithelial‑mesenchymal transition (EMT) of OS cells. To sum up, CASC15 promoted the proliferation of OS cells in vitro and the growth of OS xenograft tumors in vivo. Moreover, CASC15 promoted the entry of β‑catenin into the nucleus, thus activating the Wnt pathway and subsequently promoting the EMT of OS cells.

Project description:BackgroundNeuro-oncological ventral antigen 1 (NOVA1) is a neuron-specific RNA-binding protein which regulates alternative splicing in the developing nervous system. Recent research has found that NOVA1 plays a significant role in carcinogenesis. In this paper, we examine the role of NOVA1 in non-small cell lung cancer (NSCLC) and its underlying molecular mechanisms.MethodsThe expression of NOVA1 in NSCLC was detected by immunohistochemistry and correlations between NOVA1 expression and clinicopathological factors were analyzed by chi-square tests. Kaplan-Meier survival analysis and the Cox regression model were used to evaluate the predictive effect of prognostic factors. Western blotting, Cell Counting Kit-8, colony formation, apoptosis, migration and invasion assays were used to detect the effects of silencing (si)NOVA1 RNA on Wnt/β-catenin signaling and biological behavior in NSCLC cell lines.ResultsOur study showed that expression of NOVA1 was up-regulated and significantly correlated with poor differentiation (p = 0.020), advanced TNM stage (P = 0.001), T stage (P = 0.001) and lymph node metastasis (P = 0.000) as well as the expression of β-catenin (P = 0.012) in NSCLC. The down-regulation of NSCLC by siRNA significantly inhibited proliferation, migration and invasion and promoted apoptosis in NSCLC cells. Expression of Wnt signaling molecules, including β-catenin, activated β-catenin, cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-7, was also significantly reduced by siNOVA1. The inhibition of Wnt/β-catenin signaling in A549 and H1299 cells by siNOVA1 was reversed after treatment with a β-catenin expression plasmid.ConclusionThe present study suggests that NOVA1 may serve as a potential prognosis biomarker in NSCLC. High NOVA1 expression was associated with poor survival rate. Finally, in vitro experiments verified that NOVA1 promotes NSCLC cell proliferation and invasion by regulating Wnt/β-catenin signaling.

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ZNF671 Inhibits the Proliferation and Metastasis of NSCLC via the Wnt/?-Catenin Pathway.

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ZNF671 Inhibits the Proliferation and Metastasis of NSCLC via the Wnt/β-Catenin Pathway.

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