Ubiquitin-conjugating enzyme E2C regulates apoptosis-dependent tumor progression of non-small cell lung cancer via ERK pathway

Zhang, Zhongmian; Liu, Ping; Wang, Jian; Gong, Ting; Zhang, Fang; Ma, Jun; Han, Ning

doi:10.1007/s12032-015-0609-8

Cited by 38 publications

(32 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Ubiquitin-conjugating enzyme E2C ( UBE2C ), which encodes a member of the E2 ubiquitin-conjugating enzyme family, had been reported to serve momentous roles in various malignancies, including breast cancer, colorectal cancer, and hepatocellular carcinoma ( Ieta et al, 2007 ; Loussouarn et al, 2009 ; Chen et al, 2010 ; Bavi et al, 2011 ). For lung cancer, a study showed that progression-free survival and poorer OS of NSCLC patients was associated with UBE2C overexpression ( Kadara et al, 2009 ; Zhang et al, 2015 ). Kinesin family member 20A ( KIF20A ) belongs to the kinesin superfamily-6, a microtubule-correlated motor protein, is required for cell cycle mitosis ( Yan et al, 2012 ; Zhang et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis

Liu

et al. 2018

Front. Genet.

109

View full text Add to dashboard Cite

Background and Objective: Non-small cell lung cancer (NSCLC) accounts for 80–85% of all patients with lung cancer and 5-year relative overall survival (OS) rate is less than 20%, so that identifying novel diagnostic and prognostic biomarkers is urgently demanded. The present study attempted to identify potential key genes associated with the pathogenesis and prognosis of NSCLC.Methods: Four GEO datasets (GSE18842, GSE19804, GSE43458, and GSE62113) were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) between NSCLC samples and normal ones were analyzed using limma package, and RobustRankAggreg (RRA) package was used to conduct gene integration. Moreover, Search Tool for the Retrieval of Interacting Genes database (STRING), Cytoscape, and Molecular Complex Detection (MCODE) were utilized to establish protein–protein interaction (PPI) network of these DEGs. Furthermore, functional enrichment and pathway enrichment analyses for DEGs were performed by Funrich and OmicShare. While the expressions and prognostic values of top genes were carried out through Gene Expression Profiling Interactive Analysis (GEPIA) and Kaplan Meier-plotter (KM) online dataset.Results: A total of 249 DEGs (113 upregulated and 136 downregulated) were identified after gene integration. Moreover, the PPI network was established with 166 nodes and 1784 protein pairs. Topoisomerase II alpha (TOP2A), a top gene and hub node with higher node degrees in module 1, was significantly enriched in mitotic cell cycle pathway. In addition, Interleukin-6 (IL-6) was enriched in amb2 integrin signaling pathway. The mitotic cell cycle was the most significant pathway in module 1 with the highest P-value. Besides, five hub genes with high degree of connectivity were selected, including TOP2A, CCNB1, CCNA2, UBE2C, and KIF20A, and they were all correlated with worse OS in NSCLC. Conclusion: The results showed that TOP2A, CCNB1, CCNA2, UBE2C, KIF20A, and IL-6 may be potential key genes, while the mitotic cell cycle pathway may be a potential pathway contribute to progression in NSCLC. Further, it could be used as a new biomarker for diagnosis and to direct the synthesis medicine of NSCLC.

show abstract

Section: Discussionmentioning

confidence: 99%

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis

Liu

et al. 2018

Front. Genet.

109

View full text Add to dashboard Cite

show abstract

“…Ubiquitin-conjugating enzyme E2 C ( UBE2C ), a member of the E2 ubiquitin-conjugating enzyme family, was required for the destruction of mitotic cyclins and for cell cycle progression and may be involved in cancer progression. It was reported to be a promising biomarker in tumor progression and prognosis [29] , [30] , [31] , [32] .…”

Section: Discussionmentioning

confidence: 99%

Co-expression network analysis identified six hub genes in association with progression and prognosis in human clear cell renal cell carcinoma (ccRCC)

et al. 2017

View full text Add to dashboard Cite

Human clear cell renal cell carcinoma (ccRCC) is one of the most common types of malignant adult kidney tumors. We constructed a weighted gene co-expression network to identify gene modules associated with clinical features of ccRCC (n = 97). Six hub genes (CCNB2, CDC20, CEP55, KIF20A, TOP2A and UBE2C) were identified in both co-expression and protein-protein interaction (PPI) networks, which were highly correlated with pathologic stage. The significance of expression of the hub genes in ccRCC was ranked top 4 among all cancers and correlated with poor prognosis. Functional analysis revealed that the hub genes were significantly enriched in cell cycle regulation and cell division. Gene set enrichment analysis suggested that the samples with highly expressed hub gene were correlated with cell cycle and p53 signaling pathway. Taken together, six hub genes were identified to be associated with progression and prognosis of ccRCC, and they might lead to poor prognosis by regulating p53 signaling pathway.

show abstract

“…Recently, E2 ubiquitin conjugating enzyme UBE2C was reported to be overexpressed in multiple human tumors and might be served as a potential cancer biomarker [ 17 , 18 ]. In NSCLC, overexpression of UBE2C in tumor tissues was correlated with advanced tumor stage and apoptosis dependent cell proliferation [ 19 ]. Another study in breast cancer indicated that UBE2C down-regulation promoted the chemosensitivity of epirubicin and docetaxel resistant breast cancer cells [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Ubiquitin conjugating enzyme E2 L3 promoted tumor growth of NSCLC through accelerating p27kip1 ubiquitination and degradation

Zhao

Yang

et al. 2017

Oncotarget

View full text Add to dashboard Cite

The molecular pathogenesis of human lung cancer has not been completely clarified. Here, we reported that UBE2L3, a member of the ubiquitin-conjugating enzymes (E2s), were overexpressed in non-small-cell lung cancer (NSCLC) tissues compared with the non-tumor tissues. High expression of UBE2L3 was correlated with advanced tumor stage and adverse outcomes. Knockdown of UBE2L3 inhibited NSCLC cell growth while ectopic expression of UBE2L3 promoted NSCLC cell growth in a cell cycle dependent manner. The results of subcutaneous tumor xenograft studies revealed that knockdown of UBE2L3 attenuated the in vivo tumor growth. Mechanistically, we observed that UBE2L3 could interact with F-box protein Skp2, a member of the SCF (Skp2) ubiquitin ligase complex, and thus promoted the ubiquitination and proteasomal degradation of p27kip1. Furthermore, NSCLC cases with high level of UBE2L3 and low level of p27kip1 had worst prognosis, suggesting that combination of UBE2L3 and p27kip1 is a more powerful prognostic marker for NSCLC patients. Taken together, the current study presented a novel marker for predicting prognosis and a potential therapeutic target for NSCLC patients.

show abstract

Ubiquitin-conjugating enzyme E2C regulates apoptosis-dependent tumor progression of non-small cell lung cancer via ERK pathway

Cited by 38 publications

References 22 publications

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis

Identification of Candidate Biomarkers Correlated With the Pathogenesis and Prognosis of Non-small Cell Lung Cancer via Integrated Bioinformatics Analysis

Co-expression network analysis identified six hub genes in association with progression and prognosis in human clear cell renal cell carcinoma (ccRCC)

Ubiquitin conjugating enzyme E2 L3 promoted tumor growth of NSCLC through accelerating p27kip1 ubiquitination and degradation

Contact Info

Product

Resources

About