Uridine‐cytidine kinase 2 (<scp>UCK</scp>2): A potential diagnostic and prognostic biomarker for lung cancer

Wu, Yingjie; Jamal, Muhammad; Xie, Tian; Sun, Jiaxing; Song, Tianbao; Yin, Qian; Li, Jingyuan; S, Pan; Zeng, Xingruo; Xie, Songping; Zhang, Qiuping

doi:10.1111/cas.14125

Cited by 36 publications

(33 citation statements)

References 34 publications

(36 reference statements)

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“…Functionally, UCK2 is a pyrimidine ribonucleotide kinase that catalyzes phosphorylation of uridine to uridine monophosphate and cytidine to cytidine monophosphate. Overexpression of UCK2 is regarded as an indicator of unfavorable prognosis in various cancers, including HCC, pancreatic cancer, breast cancer, and lung cancer ( 34 – 37 ). However, few studies have revealed the detailed mechanisms underlying the regulation of UCK2.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2

et al. 2020

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The long noncoding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) has emerged as a novel player in hepatocellular carcinoma (HCC). Hypoxia is a common characteristic of the microenvironment of HCC. This study aimed to investigate whether lncRNA-NEAT1 is induced by hypoxia in HCC, and the mechanism that underlies LncRNA-NEAT1 function. Methods: The expression changes of lncRNA-NEAT1 in HCC cell lines under hypoxic conditions were examined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The regulatory effect of HIF-1α on lncRNA-NEAT1 was confirmed with chromatin immunoprecipitation (ChIP) and luciferase reporter assays. The function of lncRNA-NEAT1 on HCC cell growth under hypoxic conditions was determined by CCK-8 assay and flow cytometry. lncRNA-NEAT1 was predicted to serve as a competing endogenous RNA (ceRNA) within microRNA (miRNA)/mRNA axes based on microarray data, public HCC-related datasets and integrative bioinformatics analysis, and the miR-199a-3p/UCK2 axis was selected and validated by qRT-PCR, western blotting, RNA immunoprecipitation, and luciferase reporter analyses. The role of miR-199a-3p/UCK2 in HCC and its functional association with lncRNA-NEAT1 were assessed both in vitro and in vivo. Results: LncRNA-NEAT1 expression was significantly induced by hypoxia in SNU-182 and HUH7 cells. HIF-1α was shown to regulate lncRNA-NEAT1 transcription. Under hypoxic conditions, lncRNA-NEAT1 maintained the growth of HCC cells and inhibited apoptosis and cell cycle arrest. LncRNA-NEAT1 was predicted to regulate a panel of HCC-associated miRNA-mRNA pairs consisting of 8 miRNAs and 13 mRNAs. LncRNA-NEAT1 was shown to function as a ceRNA of miR-199a-3p/UCK2 both in HCC cells under hypoxic conditions and in an animal model. Conclusion: LncRNA-NEAT1 is a hypoxia-responsive lncRNA in HCC cell lines Insilico evidence suggested that LncRNA-NEAT1 may sustainthe growth of HCC cells by Zhang et al. LncRNA-NEAT1 in HCC Under Hypoxia regulating HCC-associated mRNAs that interact with tumor-suppressive miRNAs. The lncRNA-NEAT1/miR-199a-3p/UCK2 pathway may contribute to the progression of HCC cell lines in a hypoxic microenvironment and therefore may represent a novel therapeutic target for HCC.

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Section: Discussionmentioning

confidence: 99%

Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2

et al. 2020

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“…In recent years, a variety of bioinformatics methods have contributed greatly to the discovery of biomarkers associated with tumor development, diagnosis and prognosis (5)(6)(7)(8). The combined use of multiple databases of biological information for the analysis of cancer has also yielded certain breakthroughs.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential key genes in gastric cancer using bioinformatics analysis

Wang

Zhao

et al. 2020

biom rep

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Gastric cancer (GC) is one of the most common types of cancer worldwide. Patients must be identified at an early stage of tumor progression for treatment to be effective. The aim of the present study was to identify potential biomarkers with diagnostic value in patients with GC. To examine potential therapeutic targets for GC, four Gene Expression Omnibus (GEO) datasets were downloaded and screened for differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently performed to study the function and pathway enrichment of the identified DEGs. A protein-protein interaction (PPI) network was constructed. The CytoHubba plugin of Cytoscape was used to calculate the degree of connectivity of proteins in the PPI network, and the two genes with the highest degree of connectivity were selected for further analysis. Additionally, the two DEGs with the largest and smallest log Fold Change values were selected. These six key genes were further examined using Oncomine and the Kaplan-Meier plotter platform. A total of 99 upregulated and 172 downregulated genes common to all four GEO datasets were screened. The DEGs were primarily enriched in the Biological Process terms: 'extracellular matrix organization', 'collagen catabolic process' and 'cell adhesion'. These three KEGG pathways were significantly enriched in the categories: 'ECM-receptor interaction', 'protein digestion and absorption', and 'focal adhesion'. Based on Oncomine, expression of ATP4A and ATP4B were downregulated in GC, whereas expression of the other genes were all upregulated. The Kaplan-Meier plotter platform confirmed that upregulated expression of the identified key genes was significantly associated with worse overall survival of patients with GC. The results of the present study suggest that FN1, COL1A1, INHBA and CST1 may be potential biomarkers and therapeutic targets for GC. Additional studies are required to explore the potential value of ATP4A and ATP4B in the treatment of GC.

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“…Uridine-cytidine kinase 2 (UCK2) and ODF2 have not been studied in EnCa. UCK2 was proved to promote migration and invasion of hepatocellular carcinoma cells [ 41 ], which was also seen to be a latent diagnostic and prognostic indicator for lung cancer [ 42 ]. Overexpression of UCK2 was exhibited to be correlated with breast cancer progression and worse prognosis [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Establishment of a novel cell cycle-related prognostic signature predicting prognosis in patients with endometrial cancer

Liu

Mei

et al. 2020

Cancer Cell Int

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Background Endometrial cancer (EnCa) ranks fourth in menace within women’s malignant tumors. Large numbers of studies have proven that functional genes can change the process of tumors by regulating the cell cycle, thereby achieving the goal of targeted therapy. Methods The transcriptional data of EnCa samples obtained from the TCGA database was analyzed. A battery of bioinformatics strategies, which included GSEA, Cox and LASSO regression analysis, establishment of a prognostic signature and a nomogram for overall survival (OS) assessment. The GEPIA and CPTAC analysis were applied to validate the dysregulation of hub genes. For mutation analysis, the “maftools” package was used. Results GSEA identified that cell cycle was the most associated pathway to EnCa. Five cell cycle-related genes including HMGB3, EZH2, NOTCH2, UCK2 and ODF2 were identified as prognosis-related genes to build a prognostic signature. Based on this model, the EnCa patients could be divided into low- and high-risk groups, and patients with high-risk score exhibited poorer OS. Time-dependent ROC and Cox regression analyses revealed that the 5-gene signature could predict EnCa prognosis exactly and independently. GEPIA and CPTAC validation exhibited that these genes were notably dysregulated between EnCa and normal tissues. Lower mutation rates of PTEN, TTN, ARID1A, and etc. were found in samples with high-risk score compared with that with low-risk score. GSEA analysis suggested that the samples of the low- and high-risk groups were concentrated on various pathways, which accounted for the different oncogenic mechanisms in patients in two groups. Conclusion The current research construct a 5-gene signature to evaluate prognosis of EnCa patients, which may innovative clinical application of prognostic assessment.

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Uridine‐cytidine kinase 2 (UCK2): A potential diagnostic and prognostic biomarker for lung cancer

Cited by 36 publications

References 34 publications

Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2

Hypoxia-Induced lncRNA-NEAT1 Sustains the Growth of Hepatocellular Carcinoma via Regulation of miR-199a-3p/UCK2

Identification of potential key genes in gastric cancer using bioinformatics analysis

Establishment of a novel cell cycle-related prognostic signature predicting prognosis in patients with endometrial cancer

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