JAB1 regulates CPNE1-related differentiation via direct binding to CPNE1 in HiB5 hippocampal progenitor cells

Yoo, Jae Cheal; Park, Nammi; Choi, Hye Young; Park, Jae Yong; Yi, Gwan Su

doi:10.1016/j.bbrc.2018.02.101

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…Also, CPNE1 mediated NF-kB signaling by facilitating TNF-α-dependent Inhibitory-κB (IkB) degradation [ 40 , 41 ]. Via interacting directly with p65, CPNE1 lead to shear of p65 N-terminus and terminated the transcription of NF-kB, which in turn inhibited transcriptional activation of NF-kB [ 42 ]. It had been recognized that NF-kB was linked to multiple behaviors of cancer cells, including cell proliferation, apoptosis, migration and invasion [ 43 ] and played pivotal functions in initiation and progression of many malignancies (breast cancer, lung cancer, gastric cancer) [ 44 – 47 ].…”

Section: Discussionmentioning

confidence: 99%

CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma

Huang

Wang

et al. 2022

Cancer Cell Int

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Background Copine1 (CPNE1), the first discovered CPNE1 family member, participates in the process of carcinogenesis and development of diverse tumors. Our study aimed to investigate the expression and prognostic value of CPNE1 gene in hepatocellular carcinoma (HCC), to explore its functional network in HCC and its effects on biological behaviors. Methods HCCDB, CCLE, HPA and LinkedOmics online databases were used to explore the expression of CPNE1 gene and analyze the co-expression network of CPNE1 in hepatocellular carcinoma. Gene set enrichment analysis (GSEA) was used for GO functional annotation, KEGG pathway enrichment analysis and regulators of CPNE1 networks in LIHC. HepG2 and MHCC-97H cells were selected to construct CPNE1 knockdown cell lines by transfection with siRNA, and Hep3B cell was selected to construct CPNE1 overexpression cell line by transfection with plasmid. The effect of CPNE1 on the proliferation of hepatocellular carcinoma cells was examined by CCK8 assay and clone formation assay; the effect of CPNE1 on the migration ability of hepatocellular carcinoma cells was assessed by cell scratch assay and Transwell cell migration assay; finally, the expression of related signaling pathway proteins was examined by Western Blot. The correlation of CPNE1 expression with immune infiltration and immune checkpoint molecules in HCC tissues was analyzed using TIMER online database and GSEA. Results CPNE1 was highly expressed in HCC tissues and significantly correlated with sex, age, cancer stage and tumor grade. Overall survival (OS) was significantly lower in patients with high CPNE1 expression than in patients with low CPNE1 expression, and CPNE1 could be used as an independent prognostic indicator for HCC. Knockdown of CPNE1 gene inhibited the AKT/P53 pathway, resulting in decreased proliferation, migration and invasion of HCC cells. Overexpression of CPNE1 gene showed the opposite results. The level of CPNE1 expression in HCC was significantly and positively correlated with the level of infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (P < 0.001). GSEA results also showed that CPNE1 of LIHC was involved in some immune response regulating signaling pathways. Conclusions Our study firstly found the expression of CPNE1 was significantly higher in LIHC tissues than in normal liver tissues, and high CPNE1 expression was associated with poor prognosis. In addition, we identified the possible mechanism by which CPNE1 functioned in LIHC. CPNE1 influenced AKT/P53 pathway activation and LIHC cell proliferation and migration. There was a significant correlation between CPNE1 expression and tumor immune infiltration in LIHC.

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Section: Discussionmentioning

confidence: 99%

CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma

Huang

Wang

et al. 2022

Cancer Cell Int

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“…Also, CPNE1 mediated NF-kB signaling by facilitating TNF-α-dependent Inhibitory-κB (IkB) degradation [36]. Via interacting directly with p65, CPNE1 lead to shear of p65 Nterminus and terminated the transcription of NF-kB, which in turn inhibited transcriptional activation of NF-kB [37]. It had been recognized that NF-kB was linked to multiple behaviors of cancer cells, including cell proliferation, apoptosis, migration and invasion [38] and played pivotal functions in initiation and progression of many malignancies (breast cancer, lung cancer, gastric cancer) [39][40][41][42].…”

Section: Discussionmentioning

confidence: 99%

Exploring the Prognostic Value and Biological Function of CPNE1 Gene in Hepatocellular Carcinoma

Huang

Wang

et al. 2021

Preprint

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BackgroundLiver hepatocellular carcinoma (LIHC), the major histology subtype of primary liver cancer, accounts for 70-80% proportion of total liver cancer cases. Copine1 (CPNE1), the first discovered CPNE1 family member, participates in the process of carcinogenesis and development of diverse tumors. Our study aimed to investigate the expression and prognostic value of CPNE1 gene in hepatocellular carcinoma (HCC), to explore its functional network in HCC and its effects on biological behaviors such as proliferation, migration and invasion of HCC cells, and to explore its related signaling pathways.METHODSHCCDB, CCLE and HPA online databases were used to explore the expression of CPNE1 gene in HCC tissues; LinkedOmics online database was used to analyze the co-expression network of CPNE1 in hepatocellular carcinoma, and gene set enrichment analysis (GSEA) was used for GO functional annotation, KEGG pathway enrichment analysis, kinase target enrichment, miRNA target enrichment and transcription factor target enrichment analysis. The expression levels of CPNE1 in normal hepatocytes and several hepatocellular carcinoma cell lines were detected by RT-qPCR, and finally HepG2 and MHCC-97H cells were selected to construct CPNE1 knockdown cell lines by transfection with siRNA, and the knockdown efficiency was detected by Western Blot and RT-qPCR. The effect of CPNE1 knockdown on the proliferation of hepatocellular carcinoma cells was examined by CCK8 assay and clone formation assay; the effect of CPNE1 knockdown on the migration ability of hepatocellular carcinoma cells was assessed by cell scratch assay and Transwell cell migration assay; finally, the expression of related signaling pathway proteins was examined by Western Blot. The correlation of CPNE1 expression with immune infiltration and immune checkpoint molecules in HCC tissues was analyzed using TIMER online database.RESULTSAnalysis in several databases showed that CPNE1 was highly expressed in HCC tissues and significantly correlated with sex, age, cancer stage and tumor grade. Overall survival (OS) was significantly lower in patients with high CPNE1 expression than in patients with low CPNE1 expression, and CPNE1 could be used as an independent prognostic indicator for HCC. GSEA analysis showed that co-expressed genes of CPNE1 were mainly involved in biological processes such as establishment of protein localization to membrane, ribonucleoprotein complex biogenesis and lipid localization. Q-PCR showed that CPNE1 expression was upregulated in HCC cells compared with normal hepatocytes, and knockdown of CPNE1 gene inhibited the AKT/P53 pathway, resulting in decreased proliferation, migration and invasion of HCC cells. The level of CPNE1 expression in HCC was significantly and positively correlated with the level of infiltration of B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p<0.001), and with the expression of immune checkpoint molecules PDCD1, CD274, CTLA4, LAG3, HAVCR2, and TIGIT.CONCLUSIONThe expression of CPNE1 was significantly higher in HCC tissues than in normal liver tissues, and high CPNE1 expression was associated with poor prognosis. Knockdown of CPNE1 inhibited AKT/P53 pathway activation and suppressed HCC cell proliferation and migration. There was a significant correlation between CPNE1 expression and tumor immune infiltration in HCC.

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“…Various studies have proven that CPNE1 plays a calciumindependent role in neuronal differentiation via AKT phosphorylation [11,12]. Moreover, it can interact with partner proteins, such as 14-3-3γ and JAB1, to induce intracellular signal transduction regulating the functions of neuronal stem cells [13,14]. In addition to functioning in neuronal differentiation, CPNE1, along with Annexin A1 and Annexin A5, can also regulate the process of autophagosome maturation in Ca2+-dependent manner [15,16].…”

Section: Ivyspringmentioning

confidence: 99%

MiR-195-5p is a Potential Factor Responsible for CPNE1 Differential Expression between Subtypes of Non-Small Cell Lung Cancer

Liu

Zhang

et al. 2020

J. Cancer

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Purpose: Lung cancer is the most common malignancy with poor 5-year survival among men and women. Previous studies have shown that CPNE1 is up-regulated in non-small cell lung cancer (NSCLC). However, whether and how CPNE1 expression varies between different subtypes of NSCLC remains less understood. Methods: Bioinformatical analysis and GSE19188 were selected to confirm CPNE1 expression in different subtypes of NSCLC. Four microRNA prediction websites and GSE53883, GSE43000 were used to evaluate the possible targeting microRNAs. Kaplan-Meier survival curves were drawn based on Tumor Lung Bild-114 dataset using R2, UCSC Xena browser or linkedomics platform. Furthermore, we verified our prediction via qRT-PCR, and western blot and luciferase reporter assays. Results: we demonstrated that higher CPNE1 expression was associated with poorer survival in NSCLC patients. Moreover, among the different subtypes, patients with squamous cell lung cancer (SCC) exhibited higher level of CPNE1 expression, as well as substantially poorer survival. MiR-195-5p was down-regulated in NSCLC tissues. Interestingly, SCC patients showed lower miR-195-5p expression compared to patients with lung adenocarcinoma (ADC). In addition, functional assays proved that miR-195-5p overexpression inhibited the proliferation, migration, and invasion of NSCLC-derived cells by directly targeting CPNE1. Pathway analysis showed decreased expression of p-AKT, pErk , and Snail after transfection with miR-195-5p mimics in both lung adenocarcinoma and squamous cell lines. Conclusion: Our findings suggested that miR-195-5p regulation contributed to the differential expression of CPNE1 in NSCLC subtypes.

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JAB1 regulates CPNE1-related differentiation via direct binding to CPNE1 in HiB5 hippocampal progenitor cells

Cited by 11 publications

References 23 publications

CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma

CPNE1 is a potential prognostic biomarker, associated with immune infiltrates and promotes progression of hepatocellular carcinoma

Exploring the Prognostic Value and Biological Function of CPNE1 Gene in Hepatocellular Carcinoma

MiR-195-5p is a Potential Factor Responsible for CPNE1 Differential Expression between Subtypes of Non-Small Cell Lung Cancer

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