Increased CDCA2 Level Was Related to Poor Prognosis in Hepatocellular Carcinoma and Associated With Up-Regulation of Immune Checkpoints

Tang, Mengying; Liao, Mingchu; Ai, Xiaohong; He, Guicheng

doi:10.3389/fmed.2021.773724

Cited by 6 publications

(8 citation statements)

References 30 publications

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“…The potential use of this aptamer in HCC immunotherapy was previously explored 38 . It was also found that the upregulation of immune checkpoint CD274 could increase the expression of cell division cycle-associated protein 2 (CDCA2) and predict the poor prognosis of HCC 39 . We found that ACTG1, E2F3, RASSF3, and WDR76 in the ceRNA network are closely related to the immune checkpoints, suggesting that the ceRNA network regulates the immune escape of HCC cells.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel circRNA–miRNA–mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis

Zhong

Lin

Huang

2023

Sci Rep

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In recent years, circular RNAs (circRNAs) have been found to play an essential regulatory role in hepatocellular carcinoma (HCC) through various mechanisms, particularly the endogenous competitive RNA (ceRNA) mechanism. Therefore, it is significant to explore the circRNAs in hepatoma. In this study, we constructed the ceRNA and survival network using Cytoscape. We also used R, Perl software, and multiple online databases and platforms, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), to perform overall survival, immune cell infiltration, immune checkpoints, pathway activity, and anticancer drug sensitivity analysis of the genes. Finally, the receiver operator characteristic curve (ROC) analysis was performed to identify the diagnosis value of the genes. KEGG analysis revealed the T cell receptor signaling pathway as the main enrichment pathway. A total of 29 genes related to survival and prognosis were screened out. The findings suggest that ZNF544, WDR76, ACTG1, RASSF3, E2F3, ASRGL1, and POGK are associated with multilevel immune cell infiltration. Additionally, immune checkpoint analysis screened out the ACTG1, E2F3, RASSF3, and WDR76. It was also revealed that the WDR76, E2F3, ASRGL1, and POGK mainly activated the cell cycle and DNA damage response (DDR) pathway. The results suggest that the sensitivity toward trametinib, refametinib (RDEA119), and selumetinib correlates to the expression of WDR76. ROC analysis showed that the area under the curve (AUC) of all genes in the regulatory axis was greater than 0.7. The identified hsa_circ_0000417/hsa_circ_0002688/hsa_circ_0001387--hsa-miR-199a-5p--WDR76 regulatory axis may provide new insights into the progression, clinical diagnosis, and treatment of HCC.

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Section: Discussionmentioning

confidence: 99%

Identification of a novel circRNA–miRNA–mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis

Zhong

Lin

Huang

2023

Sci Rep

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“…In addition to reports, which revealed that overexpression of CDCA2 is a common event in lung, prostate, and oral cancers, Tang et al reported that CDCA2 was increased in HCC as well based on analyses of data from TCGA [ 17 ]. Furthermore, they suggested that CDCA2 had a high diagnostic power and was associated with poor survival for HCC [ 17 ]. On the basis of these reports, we investigated the effects of CDCA2 on the malignant behaviors of HCC cells using biological experiments in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…For example, activation of AKT–mTOR pathway contributes to the progression of lung cancer, breast cancer, endometrial cancer, and HCC [ 27 – 30 ]. Using gene set enrichment analysis, Tang et al demonstrated that CDCA2 may be involved in mTOR pathway [ 17 ]. Consistently, by biological experiments, we discovered that overexpression of CDCA2 triggered the increasing of phosphorylation of mTOR and AKT in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Besides, CDCA2 high expression may be closely related to oral squamous cell carcinoma, a types of head and neck squamous cell carcinoma (OSCC) development by blocking cell cycle arrest and apoptosis [16]. In addition to reports, which revealed that overexpression of CDCA2 is a common event in lung, prostate, and oral 5 Analytical Cellular Pathology cancers, Tang et al reported that CDCA2 was increased in HCC as well based on analyses of data from TCGA [17]. Furthermore, they suggested that CDCA2 had a high diagnostic power and was associated with poor survival for HCC [17].…”

Section: Discussionmentioning

confidence: 99%

“…In 2022, Tang et al investigated the expression pattern and the prognostic value of CDCA2 in HCC based on the data from The Cancer Genome Atlas database (TCGA-LIHC) using bioinformatics methods. They revealed that CDCA2 is an independent prognostic biomarker in HCC, and enhanced expression of CDCA2 is correlated with the up-regulation of immune checkpoints [ 17 ]. However, the exact role of CDCA2 on the malignant growth of HCC cell has not been studied.…”

Section: Introductionmentioning

confidence: 99%

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CDCA2 Promotes HCC Cells Development via AKT–mTOR Pathway

Fan

Shi

et al. 2022

Analytical Cellular Pathology

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Background. Hepatocellular carcinoma (HCC) is a highly aggressive and solid malignancy with a poor prognosis. Cell division cycle associated 2 (CDCA2) is highly expressed in HCC and is considered to be closely related to the prognosis of patients with HCC. In this research, we aimed to investigate the function and potential mechanism of CDCA2 in HCC cells. Methods. Gain- and loss-of-function experiments were conducted to determine the biological function of CDCA2 in HCC cells. Quantitative reverse transcription-polymerase chain reaction and western blot were utilized to examine the Messenger RNA (mRNA) and protein levels of CDCA2 in HCC cells. The malignant behaviors of HCC cells were analyzed by several biological experiments including cell viability, cell colony formation, and transwell assays. Western blot was also implemented to examine the expression of : AKT, protein kinase B and mTOR, mammalian target of rapamycin (AKT–mTOR) pathway related proteins and Cyclin D1. Results. A significant increase of CDCA2 was observed in HCC cell lines. Upregulation of CDCA2 resulted in the enhancement of the growth, migration, and invasion of HCC cells. Inversely, depletion of CDCA2 displayed the opposite results. Furthermore, the protein levels of p-AKT, p-mTOR, and Cyclin D1 were elevated with CDCA2 upregulation and reduced with CDCA2 depletion in HCC cells. Conclusion. Our observations revealed that CDCA2 promoted the malignant development of HCC cells, and AKT–mTOR pathway might involve in the underlying mechanism.

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PPP1R81 correlates with the survival and cell proliferation in lower-grade glioma

Xiao

Jie

Zhou³

et al. 2023

Bioscience Reports

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Background: The specific functions of PPP1R81 has been elucidated in multiple cancers; however, its role in lower-grade glioma (LGG) remains unknown. In this research, we inspected the specific role of PPP1R81 in LGG.  Methods: We totally evaluated the expression pattern and prognostic role of PPP1R81 in multitudinous tumors. Subsequently, we systematically examined the connection between PPP1R81 expression and prognosis, clinical characteristics, biological functions, genetic variations, and immunological characteristics in LGG according to The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Altas (CGGA) databases. In Vitro experiments were executed to inspect the expression level and specific roles of PPP1R81 in LGG.</p>  Results: PPP1R81 was elevated in multiple tumors and was tightly linked to a poor prognosis. LGG with higher expression of PPP1R81 showed poorer prognosis compared to lower expression of PPP1R81. The results of univariate and multivariate Cox regression analyses confirmed that the expression of PPP1R81 was an independent prognostic biomarker of LGG. Immune cell infiltration, immune checkpoint genes (ICPGs), copy number alterations (CNA), and tumor mutation burden (TMB) were also closely associated with PPP1R81 expression in LGG. In vitro experiments demonstrated that PPP1R81 was upregulated and closely interrelated with cell proliferation and cell cycle in LGG.</p>  Conclusion: PPP1R81 was an independent prognostic signature and underlying therapeutic target for patients with LGG.</p>

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Increased CDCA2 Level Was Related to Poor Prognosis in Hepatocellular Carcinoma and Associated With Up-Regulation of Immune Checkpoints

Cited by 6 publications

References 30 publications

Identification of a novel circRNA–miRNA–mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis

Identification of a novel circRNA–miRNA–mRNA regulatory axis in hepatocellular carcinoma based on bioinformatics analysis

CDCA2 Promotes HCC Cells Development via AKT–mTOR Pathway

PPP1R81 correlates with the survival and cell proliferation in lower-grade glioma

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