bims-meluca 2021-05-16 papers

Mol Cell Biochem. 2021 May 10.

Octamer transcription factor-1 induces the Warburg effect via up-regulation of hexokinase 2 in non-small cell lung cancer.

Zhen Li, Jin Su, Mingming Sun, Jiaqi Song, Huanran Sun, Jun Fan, Guo Chen, Changliang Shan, Qi Qi, Shuai Zhang.

Reprogramming of energy metabolism is a hallmark of cancer which is prevalent worldwide. Octamer transcription factor-1 (OCT1) is a well-known transcription factor. However, the role of OCT1 in metabolism remodeling has not been well defined. In the present study, we found that OCT1 was up-regulated in non-small cell lung cancer (NSCLC) and correlated with poor patient survival. Further data identified that OCT1 increased glycolysis flux, promoting proliferation in lung cancer cells. Mechanistically, OCT1 facilitated the aerobic glycolysis and cell proliferation via up-regulation of hexokinase 2 (HK2), a crucial enzyme of the Warburg effect. Hence, our findings indicate that, in NSCLC, high levels of OCT1 contribute to the Warburg effect through up-regulation of HK2, linking up the OCT1/HK2 axis and cancer progression, which provide a potential biomarker and therapeutic target for NSCLC treatment.

Keywords: HK2; Non-small cell lung cancer; OCT1; Warburg effect

DOI: https://doi.org/10.1007/s11010-021-04171-9

Oncol Lett. 2021 Jun;21(6): 488

Upregulation of glucosamine-phosphate N-acetyltransferase 1 is a promising diagnostic and predictive indicator for poor survival in patients with lung adenocarcinoma.

Pengyuan Zhu, Shaorui Gu, Haitao Huang, Chongjun Zhong, Zhenchuan Liu, Xin Zhang, Wenli Wang, Shiliang Xie, Kaiqin Wu, Tiancheng Lu, Yongxin Zhou.

Lung adenocarcinoma, a type of non-small cell lung cancer, is the leading cause of cancer death worldwide. Great efforts have been made to identify the underlying mechanism of adenocarcinoma, especially in relation to oncogenes. The present study by integrating computational analysis with western blotting, aimed to understand the role of the upregulation of glucosamine-phosphate N-acetyltransferase 1 (GNPNAT1) in carcinogenesis. In the present study, publicly available gene expression profiles and clinical data were downloaded from The Cancer Genome Atlas to determine the role of GNPNAT1 in lung adenocarcinoma (LUAD). In addition, the association between LUAD susceptibility and GNPNAT1 upregulation were analyzed using Wilcoxon signed-rank test and logistic regression analysis. In LUAD, GNPNAT1 upregulation was significantly associated with disease stage [odds ratio (OR)=2.92, stage III vs. stage I], vital status (dead vs. alive, OR=1.89), cancer status (tumor status vs. tumor-free status, OR=1.85) and N classification (yes vs. no, OR=1.75). Cox regression analysis and the Kaplan-Meier method were utilized to evaluate the association between GNPNAT1 expression and overall survival (OS) time in patients with LUAD. The results demonstrated that patients with increased GNPNAT1 expression levels exhibited a reduced survival rate compared with those with decreased expression levels (P=8.9×10-5). In addition, Cox regression analysis revealed that GNPNAT1 upregulation was significantly associated with poor OS time [hazard ratio (HR): 1.07; 95% confidence interval (CI): 1.04-1.10; P<0.001]. The gene set enrichment analysis revealed that 'cell cycle', 'oocyte meiosis', 'pyrimidine mediated metabolism', 'ubiquitin mediated proteolysis', 'one carbon pool by folate', 'mismatch repair progesterone-mediated oocyte maturation' and 'basal transcription factors purine metabolism' were differentially enriched in the GNPNAT1 high-expression samples compared with GNPNAT1 low-expression samples. The aforementioned pathways are involved in the pathogenesis of LUAD. The findings of the present study suggested that GNPNAT1 upregulation may be considered as a promising diagnostic and prognostic biomarker in patients with LUAD. In addition, the aforementioned pathways may be pivotal pathways perturbed by the abnormal expression of GNPNAT1 in LUAD. The findings of the present study demonstrated the therapeutic value of the regulation of GNPNAT1 in lung adenocarcinoma.

Keywords: glucosamine-phosphate N-acetyltransferase 1; independent predictor; lung adenocarcinoma; poor survival; upregulation

DOI: https://doi.org/10.3892/ol.2021.12750

Cancer Med. 2021 May 15.

Identification of a glycolysis-related gene signature associated with clinical outcome for patients with lung squamous cell carcinoma.

Ziming Xu, Shiwei Zhang, Fulai Nian, Shangyu Xu.

BACKGROUND: Lung squamous cell carcinoma (LUSC), one of the main types of lung cancer, has caused a huge social burden. There has been no significant progress in its therapy in recent years, Resulting in a poor prognosis. This study aims to develop a glycolysis-related gene signature to predict patients' survival with LUSC and explore new therapeutic targets.
METHODS: We obtained the mRNA expression and clinical information of 550 patients with LUSC from the Cancer Genome Atlas (TCGA) database. Glycolysis genes were identified by Gene Set Enrichment Analysis (GSEA). The glycolysis-related gene signature was established using the Cox regression analysis.
RESULTS: We developed five glycolysis-related genes signature (HKDC1, AGL, ALDH7A1, SLC16A3, and MIOX) to calculate each patient's risk score. According to the risk score, patients were divided into high- and low-risk groups and exhibited significant differences in overall survival (OS) between the two groups. The ROC curves showed that the AUC was 0.707 for the training cohort and 0.651 for the validation cohort. Additionally, the risk score was confirmed as an independent risk factor for LUSC patients by Cox regression analysis.
CONCLUSION: We built a gene signature to clarify the connection between glycolysis and LUSC. This model performs well in evaluating patients' survival with LUSC and provides new biomarkers for targeted therapy.

Keywords: gene signature; glycolysis; lung squamous cell carcinoma; survival

DOI: https://doi.org/10.1002/cam4.3945