A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma

Liu, Yingyi; Yao, Yijun; Liu, Bo; Zhang, Hao; Yang, Zhangshuo; Xia, Peng; Jiang, Xiang; Ma, Weijie; Wu, Xiaoling; Mei, Chengjie; Wang, Ganggang; Gao, Meng; Xu, Kequan; GongYe, Xiangdong; Cheng, Zhigang; Jiang, Ping; Chen, Xi; Yua, Yuan

doi:10.7150/ijbs.69495

Cited by 18 publications

(17 citation statements)

References 52 publications

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“…The expression levels of E2Fs (E2F1-8) were all signi cantly upregulated in LUAD tissues [13], Wang et al investigated the expression, prognosis value, mutation, and potential relationship with immunological aspects of E2Fs in LUAD by bio-informatics analysis [13].E2F1 is expressed strongly in 59.8% of ESCC and that the over-expression was correlated with tumor progression, lymph node metastasis, and poor prognosis after surgery [15]. Over-expression of E2F1 was signi cantly associated to worsen OS in all NSCLC patients followed for 200 months, as well as in LUAD patients [24],which was duplicated in HCC patients [25].…”

Section: Discussionmentioning

confidence: 99%

Prognosis Role of E2F1 in Cancer: a Meta-analysis

Wen

Liu

et al. 2022

Preprint

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Objective E2F1 has been confirmed to be highly expressed in a variety of cancers. To better understand the prognostic value of E2F1 in cancer patients, this study was conducted to comprehensively evaluate the prognostic value of E2F1 in cancer according to published data. Method PubMed, Web of Science and CNKI Database were searched until May 31th, 2022 by using key words to retrieve the published literatures on the role of E2F1 expression in the prognostic value of cancer. The literatures were identified according to the inclusion and exclusion criteria. The pooled result of hazard ratio (HR) and 95% confidence interval (CI) was calculated with Stata17.0 software. Result A total of 17 articles were included in this study involved in 4481 cancer patients. The pooled results showed that higher E2F1 expression was significantly correlated with unfavorable overall survival (OS) (HR = 1.10, 95%CI:1.03–1.16, I2 = 95.3%, PHeterogeneity=0.000) and disease-free survival (DFS) (HR = 1.41, 95%CI:1.33–1.49, I2 = 95.2%, PHeterogeneity=0.000) of cancer patients. Such a significant association of was maintained subgroup of sample size of patients (> 150: for OS, HR = 1.77, 95%CI:1.25–2.51, and for DFS, HR = 0.91, 95%CI:0.28–2.98; or < 150: for OS, HR = 1.93, 95%CI:0.94–3.06, and for DFS, HR = 4.39, 95%CI:4.05–4.76), ethnicity (Asian: for OS, HR = 1.65, 95%CI:1.19–2.29, and for DFS, HR = 1.08, 95%CI:0.25–4.61; or not Asian: HR = 3.55, 95%CI:1.92–6.55, and for DFS, HR = 2.87, 95%CI:1.15–7.14), the data from database (clinical: for OS, HR = 1.24, 95%CI: 0.54–2.82, and for DFS, HR = 1.40, 95%CI:0.40–4.94; or database: for OS, HR = 2.29, 95%CI:1.72–3.06, and for DFS, HR = 3.09, 95%CI:1.12–8.49), paper published year (after 2014: for OS, HR = 1.90, 95%CI:1.41–2.55;and for DFS,HR = 1.87, 95%CI:1.21–2.89; or before 2014: for OS, HR = 1.40, 95%CI:0.27–7.13, and for DFS, HR = 1.22, 95%CI:0.10-15.59);cancer type (female specific cancer: for OS, HR = 1.41, 95%CI:0.43–4.65, and for DFS, HR = 0.64, 95%CI:0.15–2.72; or non-gender specific cancers: for OS, HR = 2.00, 95%CI:1.30–3.09, and for DFS, HR = 2.95, 95%CI:1.47–5.91). Conclusion E2F1 could be served as a prognostic biomarker in cancer patients and higher levels of in cancer patients could predict shorter OS and DFS.

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Section: Discussionmentioning

confidence: 99%

Prognosis Role of E2F1 in Cancer: a Meta-analysis

Wen

Liu

et al. 2022

Preprint

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“…OIP5 level has been shown to be enhanced at G1 phase [ 28 ], and it is localized to chromosomes at postmitotic stage [ 28 ]. Stable binding of OIP5 to centromeres is essential for recruitment of CENP-A [ 16 , 24 , 29 ]. These findings suggest that OIP5 is involved in regulation of cell cyclin proteins.…”

Section: Discussionmentioning

confidence: 99%

“…Centromere protein U (CENPU) has been shown to accelerate the G1/S transition of hepatocellular carcinoma cell proliferation by interacting with E2F6 and affecting transcription of E2F1 [ 29 ]. The altered genes by CENPN knockdown are enriched in pathways related to cell cycle regulation [ 30 ].…”

Section: Discussionmentioning

confidence: 99%

OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

Cui

Chen

et al. 2023

Research

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Spermatogonial stem cells (SSCs) have important applications in both reproduction and regenerative medicine. Nevertheless, specific genes and signaling transduction pathways in mediating fate decisions of human SSCs remain elusive. Here, we have demonstrated for the first time that OIP5 (Opa interacting protein 5) controlled the self-renewal and apoptosis of human SSCs. RNA sequencing identified that NCK2 was a target for OIP5 in human SSCs, and interestingly, OIP5 could interact with NCK2 as shown by Co-IP (co-immunoprecipitation), IP-MS (mass spectrometry), and GST pulldown assays. NCK2 silencing decreased human SSC proliferation and DNA synthesis but enhanced their apoptosis. Notably, NCK2 knockdown reversed the influence of OIP5 overexpression on human SSCs. Moreover, OIP5 inhibition decreased the numbers of human SSCs at S and G2/M phases, while the levels of numerous cell cycle proteins, including cyclins A2, B1, D1, E1 and H, especially cyclin D1, were remarkably reduced. Significantly, whole-exome sequencing of 777 patients with nonobstructive azoospermia (NOA) revealed 54 single-nucleotide polymorphism mutations of the OIP5 gene (6.95%), while the level of OIP5 protein was obviously lower in testes of NOA patients compared to fertile men. Collectively, these results implicate that OIP5 interacts with NCK2 to modulate human SSC self-renewal and apoptosis via cell cyclins and cell cycle progression and that its mutation and/or lower expression is correlated with azoospermia. As such, this study offers novel insights into molecular mechanisms underlying the fate determinations of human SSCs and the pathogenesis of NOA, and it provides new targets for treating male infertility.

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“…Several studies have also shown that the CENP genes are associated with multiple cancer metastases, CENPA is associated with breast and kidney cancer metastasis [68], and CENPF and CENPU are associated with prostate cancer metastasis [69,70]. CENPU is also involved in hepatocellular carcinoma and lung cancer metastasis [71,72]. The G2/M phase is regulated by CENPA, CENPF, and CENPW has been documented [73].…”

Section: Discussionmentioning

confidence: 99%

Significance of centromere protein genes and their associated immune and metabolic differences in the prediction of prognosis and treatment outcome in breast cancer

Yang

Yan

Liu

et al. 2022

Preprint

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Background: Genes of the centromere protein (CENP) are involved in the kinetochore assembly during mitosis. The expression of some CENPgenes has been associated with various carcinogenesis and development. However, it is unclear whether abnormal expression of CENP genes as a unit affects the clinical outcome, immune cell infiltration, and immunotherapy of breast cancer (BRCA) patients. Methods: We systematically evaluated CENP genes and comprehensively determined the correlation between high and low expression and prognosis, staging, malignant phenotype, and drug sensitivity of BRCA. The correlation between CENP genes and immune cell infiltration was comprehensively determined. Further screening for immune- and metabolic-related hub genes was used to quantify subtypes of patients. Then, we evaluated their value in prognosis prediction and treatment response to BRCA. The correlation between CENP genes and drug resistance was also determined by sequencing the tissues of patients. Single-cell sequencing to further analyze CENP genes expression in metastatic cancer. Results: The CENP genes were significantly differentially expressed in BRCA compared to para-cancer. Highly expressed CENP genes had a poor prognosis, late stage, and a high proportion of malignant phenotypes. We identified high and low CENPclusters and observed that high expression was associated with poor prognosis, high immune escape, and reduced drug sensitivity in patients. Afterward, we screened immune- and metabolic-related hub genes and predicted the prognosis of BRCA patients based on them. Furthermore, CENP genes were elevated in drug-resistant breast cancer tissues and metastatic breast cancer tissues. Conclusion: Collectively, we determined the prognostic impact of the CENP genes on BRCA patients. Furthermore, by further screening the hub genes to subgroup breast cancer patients to predict prognosis and to be able to explore more effective treatment strategies based on the expression of CENP genes.

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A positive feedback loop of CENPU/E2F6/E2F1 facilitates proliferation and metastasis via ubiquitination of E2F6 in hepatocellular carcinoma

Cited by 18 publications

References 52 publications

Prognosis Role of E2F1 in Cancer: a Meta-analysis

Prognosis Role of E2F1 in Cancer: a Meta-analysis

OIP5 Interacts with NCK2 to Mediate Human Spermatogonial Stem Cell Self-Renewal and Apoptosis through Cell Cyclins and Cycle Progression and Its Abnormality Is Correlated with Male Infertility

Significance of centromere protein genes and their associated immune and metabolic differences in the prediction of prognosis and treatment outcome in breast cancer

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