Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression
Abstract Background Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function...
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | Journal of Experimental & Clinical Cancer Research |
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| Online Access: | https://doi.org/10.1186/s13046-021-01848-3 |
| _version_ | 1831740584192114688 |
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| author | Shijun Yu Li Li Hui Cai Bin He Yong Gao Yandong Li |
| author_facet | Shijun Yu Li Li Hui Cai Bin He Yong Gao Yandong Li |
| author_sort | Shijun Yu |
| collection | DOAJ |
| description | Abstract Background Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC. Methods NELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections. Results NELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other. Conclusion Our findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease. |
| first_indexed | 2024-12-21T14:00:56Z |
| format | Article |
| id | doaj.art-2d450dacfdee4d1a846423b4df927e4e |
| institution | Directory Open Access Journal |
| issn | 1756-9966 |
| language | English |
| last_indexed | 2024-12-21T14:00:56Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Experimental & Clinical Cancer Research |
| spelling | doaj.art-2d450dacfdee4d1a846423b4df927e4e2022-12-21T19:01:22ZengBMCJournal of Experimental & Clinical Cancer Research1756-99662021-02-0140111610.1186/s13046-021-01848-3Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expressionShijun Yu0Li Li1Hui Cai2Bin He3Yong Gao4Yandong Li5Department of Oncology, Shanghai East Hospital, Tongji University School of MedicineDepartment of Oncology, Shanghai East Hospital, Tongji University School of MedicineDepartment of Geriatrics, The Second Affiliated Hospital of Zhejiang UniversityDepartment of Oncology, Shanghai East Hospital, Tongji University School of MedicineDepartment of Oncology, Shanghai East Hospital, Tongji University School of MedicineDepartment of Oncology, Shanghai East Hospital, Tongji University School of MedicineAbstract Background Accumulating evidence has highlighted the importance of negative elongation factor complex member E (NELFE) in tumorigenesis. However, the relationship between NELFE and gastric cancer (GC) remains unclear. This study aimed to explore the expression pattern and specific function of NELFE in GC. Methods NELFE expression was evaluated by immunohistochemistry and qRT-PCR in GC tissues, respectively. Cell proliferation, migration and invasion were measured by CCK-8, colony formation, transwell assays, and nude mice model. Bioinformatics analysis was performed to search potential target genes of NELFE, and a Cignal Finder 10-Pathway Reporter Array was used to explore potential signaling pathways regulated by NELFE. Dual-luciferase reporter assays, qRT-PCR and western blotting were conducted to verify their regulatory relationship. The expression correlations among NELFE, β-catenin and CSNK2B were further explored by immunohistochemistry on consecutive resections. Results NELFE was significantly overexpressed in GC tissues both in protein and mRNA level and negatively correlated with the prognosis of GC patients. Gain- and loss-of-function experiments showed that NELFE potentiated GC cell proliferation and metastasis in vitro and in vivo. CSNK2B was identified as a downstream effector of NELFE. Wnt/β-catenin signaling may mediate the regulation of CSNK2B by NELFE. In addition, NELFE, β-catenin and CSNK2B were all remarkably upregulated in tumor tissues compared with adjacent normal tissues, and their expression levels in GC were positively correlated with each other. Conclusion Our findings reveal a new NELFE-Wnt/β-catenin-CSNK2B axis to promote GC progression and provide new candidate targets against this disease.https://doi.org/10.1186/s13046-021-01848-3NELFEWnt/β-cateninCSNK2BGastric cancerTumorigenesis |
| spellingShingle | Shijun Yu Li Li Hui Cai Bin He Yong Gao Yandong Li Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression Journal of Experimental & Clinical Cancer Research NELFE Wnt/β-catenin CSNK2B Gastric cancer Tumorigenesis |
| title | Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression |
| title_full | Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression |
| title_fullStr | Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression |
| title_full_unstemmed | Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression |
| title_short | Overexpression of NELFE contributes to gastric cancer progression via Wnt/β-catenin signaling-mediated activation of CSNK2B expression |
| title_sort | overexpression of nelfe contributes to gastric cancer progression via wnt β catenin signaling mediated activation of csnk2b expression |
| topic | NELFE Wnt/β-catenin CSNK2B Gastric cancer Tumorigenesis |
| url | https://doi.org/10.1186/s13046-021-01848-3 |
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