HIF-1α Mediates Functional Switching of TGF-Β Signaling by Regulating the PKM mRNA Splicing and Metabolic Reprogramming in Non-Small Cell Lung Cancer

2020 ◽  
Author(s):  
Yiwei Huang ◽  
Zhencong Chen ◽  
Tao Lu ◽  
Mengnan Zhao ◽  
Guoshu Bi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Mrna Splicing ◽  
Metabolic Reprogramming ◽  
Small Cell Lung ◽  
Functional Switching

scholarly journals N6-Methyladenosine RNA Methylation Regulator-Related Alternative Splicing (AS) Gene Signature Predicts Non–Small Cell Lung Cancer Prognosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhenyu Zhao ◽  
Qidong Cai ◽  
Pengfei Zhang ◽  
Boxue He ◽  
Xiong Peng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Alternative Splicing ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Regulatory Genes ◽  
Mrna Splicing ◽  
Cancer Prognosis ◽  
Small Cell Lung ◽  
Rna Methylation

Aberrant N6-methyladenosine (m6A) RNA methylation regulatory genes and related gene alternative splicing (AS) could be used to predict the prognosis of non–small cell lung carcinoma. This study focused on 13 m6A regulatory genes (METTL3, METTL14, WTAP, KIAA1429, RBM15, ZC3H13, YTHDC1, YTHDC2, YTHDF1, YTHDF2, HNRNPC, FTO, and ALKBH5) and expression profiles in TCGA-LUAD (n = 504) and TCGA-LUSC (n = 479) datasets from the Cancer Genome Atlas database. The data were downloaded and bioinformatically and statistically analyzed, including the gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. There were 43,948 mRNA splicing events in lung adenocarcinoma (LUAD) and 46,020 in lung squamous cell carcinoma (LUSC), and the data suggested that m6A regulators could regulate mRNA splicing. Differential HNRNPC and RBM15 expression was associated with overall survival (OS) of LUAD and HNRNPC and METTL3 expression with the OS of LUSC patients. Furthermore, the non–small cell lung cancer prognosis-related AS events signature was constructed and divided patients into high- vs. low-risk groups using seven and 14 AS genes in LUAD and LUSC, respectively. The LUAD risk signature was associated with gender and T, N, and TNM stages, but the LUSC risk signature was not associated with any clinical features. In addition, the risk signature and TNM stage were independent prognostic predictors in LUAD and the risk signature and T stage were independent prognostic predictors in LUSC after the multivariate Cox regression and receiver operating characteristic analyses. In conclusion, this study revealed the AS prognostic signature in the prediction of LUAD and LUSC prognosis.

scholarly journals Nrf2 Mediates Metabolic Reprogramming in Non-Small Cell Lung Cancer

2020 ◽  
Vol 10 ◽  
Author(s):  
Jiangang Zhao ◽  
Xu Lin ◽  
Di Meng ◽  
Liping Zeng ◽  
Runzhou Zhuang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
Related Factor ◽  
Small Cell Lung ◽  
Antioxidant Genes ◽  
Nrf2 Activation ◽  
Underlying Mechanisms

Nuclear factor erythroid-2–related factor-2 (NFE2L2/Nrf2) is a transcription factor that regulates the expression of antioxidant genes. Both Kelch-like ECH-associated protein 1 (Keap1) mutations and Nrf2 mutations contribute to the activation of Nrf2 in non-small cell lung cancer (NSCLC). Nrf2 activity is associated with poor prognosis in NSCLC. Metabolic reprogramming represents a cancer hallmark. Increasing studies reveal that Nrf2 activation promotes metabolic reprogramming in cancer. In this review, we discuss the underlying mechanisms of Nrf2-mediated metabolic reprogramming and elucidate its role in NSCLC. Inhibition of Nrf2 can alter metabolic processes, thus suppress tumor growth, prevent metastasis, and increase sensitivity to chemotherapy in NSCLC. In conclusion, Nrf2 may serve as a therapeutic target for the treatment of NSCLC.

Prognostic alternative mRNA splicing signature in non-small cell lung cancer

2017 ◽  
Vol 393 ◽  
pp. 40-51 ◽  
Author(s):  
Yuan Li ◽  
Nan Sun ◽  
Zhiliang Lu ◽  
Shouguo Sun ◽  
Jianbing Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Mrna Splicing ◽  
Small Cell Lung ◽  
Alternative Mrna Splicing

scholarly journals Metabolic reprogramming and Notch activity distinguish between non-small cell lung cancer subtypes

2019 ◽  
Vol 121 (1) ◽  
pp. 51-64 ◽  
Author(s):  
Katherine Sellers ◽  
Thaddeus D. Allen ◽  
Michael Bousamra ◽  
JinLian Tan ◽  
Andrés Méndez-Lucas ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
Small Cell Lung ◽  
Cancer Subtypes ◽  
Notch Activity

scholarly journals Programmed cell death ligand-1-mediated enhancement of hexokinase 2 expression is inversely related to T-cell effector gene expression in non-small-cell lung cancer

2019 ◽  
Vol 38 (1) ◽  
Author(s):  
Sehui Kim ◽  
Ji-Young Jang ◽  
Jaemoon Koh ◽  
Dohee Kwon ◽  
Young A. Kim ◽  
...  
Keyword(s):  
Lung Cancer ◽  
T Cells ◽  
T Cell ◽  
Small Cell Lung Cancer ◽  
Tumor Cells ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
Small Cell Lung ◽  
Cell Effector

Abstract Background We investigated the role of PD-L1 in the metabolic reprogramming of non-small cell lung cancer (NSCLC). Methods Changes in glycolysis-related molecules and glycolytic activity were evaluated in PD-L1low and PD-L1high NSCLC cells after transfection or knockdown of PD-L1, respectively. Jurkat T-cell activation was assessed after co-culture with NSCLC cells. The association between PD-L1 and immune response-related molecules or glycolysis were analyzed in patients with NSCLC and The Cancer Genome Atlas (TCGA). Results Transfecting PD-L1 in PD-L1low cells enhanced hexokinase-2 (HK2) expression, lactate production, and extracellular acidification rates, but minimally altered GLUT1 and PKM2 expression and oxygen consumption rates. By contrast, knocking-down PD-L1 in PD-L1high cells decreased HK2 expression and glycolysis by suppressing PI3K/Akt and Erk pathways. Interferon-γ (IFNγ) secretion and activation marker expression was decreased in stimulated Jurkat T-cells when co-cultured with HK2-overexpressing vector-transfected tumor cells rather than empty vector-transfected tumor cells. Immunohistochemistry revealed that PD-L1 expression was positively correlated with HK2 expression in NSCLC (p < 0.001). In TCGA, HK2 exhibited a positive linear association with CD274 (PD-L1) expression (p < 0.001) but an inverse correlation with the expression of CD4, CD8A, and T-cell effector function-related genes in the CD274high rather than CD274low group. Consistently, there were fewer CD8+ T-cells in PD-L1positive/HK2high tumors compared to PD-L1positive/HK2low tumors in squamous cell carcinoma. Conclusions PD-L1 enhances glycolysis in NSCLC by upregulating HK2, which might dampen anti-tumor immunity. PD-L1 may contribute to NSCLC oncogenesis by inducing metabolic reprogramming and immune checkpoint.

scholarly journals xCT (SLC7A11)-mediated metabolic reprogramming promotes non-small cell lung cancer progression

Oncogene ◽  
2018 ◽  
Vol 37 (36) ◽  
pp. 5007-5019 ◽  
Author(s):  
Xiangming Ji ◽  
Jun Qian ◽  
S. M. Jamshedur Rahman ◽  
Peter J. Siska ◽  
Yong Zou ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Progression ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
Small Cell Lung

scholarly journals Metabolic Diversity in Human Non-Small Cell Lung Cancer Cells

2019 ◽  
Author(s):  
Pei-Hsuan Chen ◽  
Ling Cai ◽  
Kenneth Huffman ◽  
Chendong Yang ◽  
Jiyeon Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cell Lung Cancer ◽  
Expression Patterns ◽  
Small Cell ◽  
Metabolic Reprogramming ◽  
Small Cell Lung

SummaryIntermediary metabolism in cancer cells is regulated by diverse cell-autonomous processes including signal transduction and gene expression patterns arising from specific oncogenotypes and cell lineages. Although it is well established that metabolic reprogramming is a hallmark of cancer, we lack a full view of the diversity of metabolic programs in cancer cells and an unbiased assessment of the associations between metabolic pathway preferences and other cell-autonomous processes. Here we quantified over 100 metabolic features, mostly from 13C enrichment of molecules from central carbon metabolism, in over 80 non-small cell lung cancer (NSCLC) cell lines cultured under identical conditions. Because these cell lines were extensively annotated for oncogenotype, gene expression, protein expression and therapeutic sensitivity, the resulting database enables the user to uncover new relationships between metabolism and these orthogonal processes.

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