Functional transcriptomic annotation and protein–protein interaction analysis identify <scp>EZH</scp>2 and <scp>UBE</scp>2C as key upregulated proteins in ovarian cancer

Martínez-Canales, Sandra; Rodas, Miguel López de; Nuncia-Cantarero, Miriam; Páez, Raquel; Amir, Eitan; Győrffy, Balázs; Pandiella, Atanasio; Galán-Moya, Eva María; Ocaña, Alberto

doi:10.1002/cam4.1406

Cited by 16 publications

(16 citation statements)

References 20 publications

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“…Overexpression of MYOF has been associated with many cancers in humans, including breast cancer, lung cancer, and pancreatic cancer, and is shown to promote tumorigenesis, tumor cell motility, proliferation, migration, and metastasis [32][33][34]. Furthermore, other studies had reported up-regulation or down-regulation of TMEM156, ELOVL5, KIF23, AMPD3, CCNB1, CENPE, UBE2C, NXPE3, and PDE4DIP to be associated with numerous types of cancers in humans, such as breast cancer, ovarian cancer, non-small cell lung cancer, clear cell renal cell carcinoma, stomach cancer, colorectal cancer, esophageal cancer, pancreatic cancer, hepatocellular cancer, lung cancer, and prostate cancer [35][36][37][38][39][40][41][42][43][44][45]. Our results were consistent with the previous findings that indicated DEGs to possibly have great implication in tumor/cancer progression.…”

Section: Discussionmentioning

confidence: 99%

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

Ishikawa

Rahman

Yamauchi

et al. 2020

Viruses

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Milk extracellular vesicles (EVs) form an excellent source of mRNAs, microRNAs (miRNAs), proteins, and lipids that represent the physiological and pathological status of the host. Recent studies have reported milk EVs as novel biomarkers for many infectious diseases in both humans and animals. For example, miRNAs in milk EVs from cattle were used for early detection of bacterial infection in the mammary gland. Based on these findings, we hypothesized that mRNAs in milk EVs are suitable for gaining a better understanding of the pathogenesis of bovine leukemia virus (BLV) infection and prognosis of the clinical stage in cattle. For that purpose, milk EVs were isolated from BLV-infected and uninfected cattle, and mRNAs were investigated using microarray analysis. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed mainly focusing on the differentially expressed genes (DEGs) in milk EVs from BLV-infected cattle. GO and KEGG analyses suggested the DEGs in milk EVs from BLV-infected cattle had involved in diverse molecular functions, biological processes, and distinct disease-related pathways. The present study suggested that BLV infection causes profound effects on host cellular activity, changing the mRNA expression profile in milk EVs obtained from BLV-infected cattle. Overall, our results suggested that the mRNA profile in milk EVs to be a key factor for monitoring the clinical stage of BLV infection. This is the first report of mRNA profiling of milk EVs obtained from BLV-infected cattle.

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Section: Discussionmentioning

confidence: 99%

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

Ishikawa

Rahman

Yamauchi

et al. 2020

Viruses

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“…Among these genes, UBE2C, TOP2A, and KIAA0101 have node degrees exceeding 20. In recent years, it was found that UBE2C was lowly expressed in normal tissues while highly expressed in a variety of tumors such as lung cancer, [ 27 ] breast cancer, [ 28 ] ovarian cancer, [ 29 ] esophageal cancer, [ 30 ] and gastric cancer. [ 31 ] Overexpression of UBE2C positively correlates to poor prognosis in tumors.…”

Section: Discussionmentioning

confidence: 99%

Identification of crucial genes associated with lung adenocarcinoma by bioinformatic analysis

Dai¹,

Zhou²,

Wang³

2020

Medicine

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Lung cancer is the world's most common malignancies and ranks first among all cancer-related deaths. Lung adenocarcinoma (LUAD) is the most frequent histological type in lung cancer. Its pathogenesis has not yet been fully elucidated, so it is of great significance to explore related genes for elucidating the molecular mechanism involved in occurrence and development of LUAD. To explore the crucial genes associated with LUAD development and progression, microarray datasets GSE7670, GSE10072, and GSE31547 were acquired from the Gene Expression Omnibus (GEO) database. R language Limma package was adopted to screen the differentially expressed genes (DEGs). The clusterProfiler package was used for enrichment analysis and annotation of the Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathways for DEGs. The Search Tool for the Retrieval of Interacting Genes database (STRING) was used to construct the protein interaction network for DEGs, while Cytoscape was adopted to visualize it. The functional module was screened with Cytoscape's MCODE (The Molecular Complex Detection) plugin. The crucial genes associated with LUAD were identified by cytoHubba plugin. Kaplan–Meier plotter online tool was used to perform survival analysis of the hub gene. Three hundred twenty-one DEGs in total were screened, of which 105 were upregulated and 216 were downregulated. It was found that some GO terms and pathways (e.g., collagen trimer, extracellular structure organization, heparin binding, complement and coagulation cascades, malaria, protein digestion and absorption, and PPAR signaling pathway) were considerably enriched in DEGs. UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, PRC1, and CDK1 were identified as crucial genes. Survival analysis showed that the overexpression of UBE2C, TOP2A, RRM2, CDC20, CCNB2, KIAA0101, BUB1B, TPX2, and PRC1 significantly reduced the overall survival of LUAD patients. One of the crucial genes: UBE2C was validated by immunohistochemistry to be upregulated in LUAD tissues. This study screened out potential biomarkers of LUAD, providing a theoretical basis for elucidating the pathogenesis and evaluating the prognosis of LUAD.

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“…However, the exact mechanism of UBE2C in HCC progression has not been elucidated. A previous study using transcriptomic functional annotation and protein–protein interacting network analyses demonstrated that the histone-lysine N-methyltransferase (EZH2) and UBE2C were identified as principal interacting proteins of druggable networks [18], implying that the EZH2–UBE2C interaction may be critical for cancer progression.…”

Section: Discussionmentioning

confidence: 99%

UBE2C functions as a potential oncogene by enhancing cell proliferation, migration, invasion, and drug resistance in hepatocellular carcinoma cells

et al. 2019

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Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality worldwide. Recently, ubiquitin-conjugating enzyme E2C (UBE2C) has been reported to be overexpressed in human cancers and act as a potential oncogene. However, little is known about the functional roles of UBE2C in HCC progression. In the present study, analysis of UBE2C mRNA expression in The Cancer Genome Atlas (TCGA) dataset reveals that significantly higher UBE2C mRNA levels was found in HCC tissues and associated with higher HCC grade. Elevated UBE2C mRNA levels in HCC indicated worsened survival probabilities. Through performing loss-of-function assays, we demonstrated that knockdown of UBE2C expression obviously suppressed proliferation, migration, and invasion of HCC cells in vitro. Moreover, HCC cells with UBE2C knockdown showed higher sensitivity for the treatment of chemotherapeutic drug, including adriamycin (ADR) and 5-fluorouracil (5-FU). Silencing of UBE2C also increased the sensitivity of HCC cells to sorafenib, an approved treatment for patients with advanced-stage HCC. Our findings strongly suggest that UBE2C emerges as a marker for prognosis in HCC, and blocking UBE2C may be a novel strategy for HCC therapies.

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Functional transcriptomic annotation and protein–protein interaction analysis identify EZH2 and UBE2C as key upregulated proteins in ovarian cancer

Cited by 16 publications

References 20 publications

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

mRNA Profile in Milk Extracellular Vesicles from Bovine Leukemia Virus-Infected Cattle

Identification of crucial genes associated with lung adenocarcinoma by bioinformatic analysis

UBE2C functions as a potential oncogene by enhancing cell proliferation, migration, invasion, and drug resistance in hepatocellular carcinoma cells

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