Low UGP2 Expression Is Associated with Tumour Progression and Predicts Poor Prognosis in Hepatocellular Carcinoma

Hu, Qiuyue; Shen, Shen; Li, Jianhao; Liu, Liwen; Liu, Xin; Zhang, Yingying; Zhou, Yongjian; Zhu, Weiwei; Yu, Yan; Cui, Guangying

doi:10.1155/2020/3231273

Cited by 12 publications

(11 citation statements)

References 32 publications

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“…The study of Wang et al suggested that overexpressed miR-93-5p enhanced the proliferation capacity of HCC by inhibiting the expression of PPARGC1A. A previous study suggested that low UGP2 expression was independently associated with poor prognosis of HCC (Hu et al, 2020). ILVBL is the major 2-OH acyl-CoA lyase involved in the cleavage reaction in the fatty acid α-oxidation of the phytosphingosine degradation pathway (Kitamura et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma

Wen

Yan

Shi

et al. 2021

Front. Mol. Biosci.

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Background: Ferroptosis, as a unique programmed cell death modality, has been found to be closely related to the occurrence and development of hepatocellular carcinoma (HCC). Hypoxia signaling pathway has been found to be extensively involved in the transformation and growth of HCC and to inhibit anti-tumor therapy through various approaches. However, there is no high-throughput study to explore the potential link between ferroptosis and hypoxia, as well as their combined effect on the prognosis of HCC.Methods: We included 370 patients in The Cancer Genome Atlas (TCGA) database and 231 patients in the International Cancer Genome Consortium (ICGC) database. Univariate COX regression and Least Absolute Shrinkage and Selection Operator approach were used to construct ferroptosis-related genes (FRGs) and hypoxia-related genes (HRGs) prognostic signature (FHPS). Kaplan–Meier method and Receiver Operating Characteristic curves were analyzed to evaluate the predictive capability of FHPS. CIBERSOR and single-sample Gene Set Enrichment Analysis were used to explore the connection between FHPS and tumor immune microenvironment. Immunohistochemical staining was used to compare the protein expression of prognostic FRGs and HRGs between normal liver tissue and HCC tissue. In addition, the nomogram was established to facilitate the clinical application of FHPS.Results: Ten FRGs and HRGs were used to establish the FHPS. We found consistent results in the TCGA training cohort, as well as in the independent ICGC validation cohort, that patients in the high-FHPS subgroup had advanced tumor staging, shorter survival time, and higher mortality. Moreover, patients in the high-FHPS subgroup showed ferroptosis suppressive, high hypoxia, and immunosuppression status. Finally, the nomogram showed a strong prognostic capability to predict overall survival (OS) for HCC patients.Conclusion: We developed a novel prognostic signature combining ferroptosis and hypoxia to predict OS, ferroptosis, hypoxia, and immune status, which provides a new idea for individualized treatment of HCC patients.

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Section: Discussionmentioning

confidence: 99%

Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma

Wen

Yan

Shi

et al. 2021

Front. Mol. Biosci.

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“…Of interest for future study are top sensitivity hit UGP2 and resistance hit COPS4 which were the most lowly expressed and highly expressed screen hits in the large chemotherapy treatment‐resistant breast cancer patient tumor cohort. Although not studied in the context of breast cancer, UGP2 expression (both high and low) has been implicated in the progression of other cancers [47,48], and our data suggest a potential uncharacterized role for UGP2 in breast cancer in the context of treatment. COPS4 is part of the multisubunit COP9 that plays roles in DNA repair and cell cycle regulation in part through modulating the activity of E3 ubiquitin ligases [49].…”

Section: Discussionmentioning

confidence: 81%

An in vivo genome‐wide shRNA screen identifies BCL6 as a targetable biomarker of paclitaxel resistance in breast cancer

et al. 2021

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Paclitaxel is a common breast cancer drug; however, some tumors are resistant. The identification of biomarkers for paclitaxel resistance or sensitivity would enable the development of strategies to improve treatment efficacy. A genome-wide in vivo shRNA screen was performed on paclitaxel-treated mice with MDA-MB-231 tumors to identify genes associated with paclitaxel sensitivity or resistance. Gene expression of the top screen hits was associated with tumor response (resistance or sensitivity) among patients who received neoadjuvant chemotherapy containing paclitaxel. We focused our validation on screen hit B-cell lymphoma 6 (BCL6), which is a therapeutic target in cancer but for which no effects on drug response have been reported. Knockdown of BCL6 resulted in increased tumor regression in mice treated with paclitaxel. Similarly, inhibiting BCL6 using a small molecule inhibitor enhanced paclitaxel treatment efficacy both in vitro and in vivo in breast cancer models. Mechanism studies revealed that reduced BCL6 enhances the efficacy of paclitaxel by inducing sustained G1/S arrest, concurrent with increased apoptosis and expression of target gene cyclindependent kinase inhibitor 1A. In summary, the genome-wide shRNA knockdown screen has identified BCL6 as a potential targetable resistance biomarker of paclitaxel response in breast cancer.

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“…Zeng et al found that UGP2 was identified as a progression marker that promotes the growth and motility of human glioma cells and performs a crucial role in the proliferation of LGG (Zeng et al, 2019). Hu et al found that low UGP2 expression was associated with tumor progression and poor prognosis for HCC (Hu et al, 2020). Nonetheless, studies on the function of UGP2 in tumors are limited, particularly in LGG.…”

Section: Discussionmentioning

confidence: 99%

N6-methyladenosine RNA methylation regulator-related alternative splicing gene signature as prognostic predictor and in immune microenvironment characterization of patients with low-grade glioma

et al. 2022

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Background: N6-methyladenosine (m6A) RNA methylation is an important epigenetic modification affecting alternative splicing (AS) patterns of genes to regulate gene expression. AS drives protein diversity and its imbalance may be an important factor in tumorigenesis. However, the clinical significance of m6A RNA methylation regulator-related AS in the tumor microenvironment has not been investigated in low-grade glioma (LGG).Methods: We used 12 m6A methylation modulatory genes (WTAP, FTO, HNRNPC, YTHDF2, YTHDF1, YTHDC2, ALKBH5, YTHDC1, ZC3H13, RBM15, METTL14, and METTL3) from The Cancer Genome Atlas (TCGA) database as well as the TCGA-LGG (n = 502) dataset of AS events and transcriptome data. These data were downloaded and subjected to machine learning, bioinformatics, and statistical analyses, including gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Univariate Cox, the Least Absolute Shrinkage and Selection Operator (LASSO), and multivariable Cox regression were used to develop prognostic characteristics. Prognostic values were validated using Kaplan-Maier survival analysis, proportional risk models, ROC curves, and nomograms. The ESTIMATE package, TIMER database, CIBERSORT method, and ssGSEA algorithm in the R package were utilized to explore the role of the immune microenvironment in LGG. Lastly, an AS-splicing factor (SF) regulatory network was examined in the case of considering the role of SFs in regulating AS events.Results: An aggregate of 3,272 m6A regulator-related AS events in patients with LGG were screened using six machine learning algorithms. We developed eight AS prognostic characteristics based on splice subtypes, which showed an excellent prognostic prediction performance. Furthermore, quantitative prognostic nomograms were developed and showed strong validity in prognostic prediction. In addition, prognostic signatures were substantially associated with tumor immune microenvironment diversity, ICB-related genes, and infiltration status of immune cell subtypes. Specifically, UGP2 has better promise as a prognostic factor for LGG. Finally, splicing regulatory networks revealed the potential functions of SFs.Conclusion: The present research offers a novel perspective on the role of AS in m6A methylation. We reveal that m6A methylation regulator-related AS events can mediate tumor progression through the immune-microenvironment, which could serve as a viable biological marker for clinical stratification of patients with LGG so as to optimize treatment regimens.

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Low UGP2 Expression Is Associated with Tumour Progression and Predicts Poor Prognosis in Hepatocellular Carcinoma

Cited by 12 publications

References 32 publications

Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma

Construction and Validation of a Combined Ferroptosis and Hypoxia Prognostic Signature for Hepatocellular Carcinoma

An in vivo genome‐wide shRNA screen identifies BCL6 as a targetable biomarker of paclitaxel resistance in breast cancer

N6-methyladenosine RNA methylation regulator-related alternative splicing gene signature as prognostic predictor and in immune microenvironment characterization of patients with low-grade glioma

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