Hippocalcin-like 1 is a key regulator of LDHA activation that promotes the growth of non-small cell lung carcinoma

Wang, Xiangyu; Xie, Xiaodong; Zhang, Yuanyuan; Ma, Fayang; Pang, Mengjun; Laster, Kyle Vaughn; Li, Xiang; Liu, Kangdong; Dong, Zigang; Kim, Dong Joon

doi:10.1007/s13402-022-00661-0

Cited by 9 publications

(8 citation statements)

References 35 publications

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“…In the present study, higher expression of LDHA indicated worse OS, which suggests that higher LDHA in LUAD might help enhance fat synthesis by promoting acetyl-CoA generation in glycolysis, thus providing more energy for tumor progression. HPCAL1 was the gene with the second-largest hazard ratio in our study, and interestingly, a recent study demonstrated that HPCAL1 could directly bind to LDHA and enhance its activation, thus influencing fatty acid synthesis and promoting NSCLC growth ( Wang et al, 2022 ). IGF2BP1 was reported to be associated with lipid accumulation in macrophages or serve as a biomarker for NSCLC; however, the relationship between IGF2BP1 and fatty acid metabolism in LUAD had not been shown ( Kato et al, 2007 ; Liu et al, 2022 ).…”

Section: Discussionsupporting

confidence: 60%

Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma

et al. 2022

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Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer. Fatty acid metabolism takes part in malignancy progression. However, the roles fatty acid metabolism plays in LUAD are still unclear.Methods: The transcriptomic and clinical data of LUAD patients from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were extracted. ssGSEA, WGCNA, univariable Cox regression, and LASSO Cox regression analyses were performed to identify the fatty acid metabolism-related genes which influenced the overall survival (OS) and build a fatty acid-related risk score (FARS) model. A nomogram was established based on the FARS and other clinicopathological features, and ROC and calibration plots were used to validate the prediction accuracy. The tumor microenvironment (TME) of patients with high and low FARS was compared.Results: A total of 38 genes were identified to be independently related to the survival outcome and put into a FARS model. High FARS patients exhibited significantly worse OS. The nomogram included the FARS and pathological stage, and the AUC of the nomogram predicting 1-, 2-, 3-, 4-, and 5-year OS was 0.789, 0.807, 0.798, 0.809, and 0.753, respectively. Calibration plots also indicated good accuracy. Moreover, the samples of the high FARS had higher expression of PDL1.Conclusion: We constructed a FARS model which could accurately predict the survival outcome of the LUAD patients. The genes of the FARS are related to the tumor microenvironment and patients with high FARS can potentially benefit more from anti-PD1/PDL1 immunotherapy. In addition, the mechanisms of the genes in the FARS affecting prognosis are worthy of further research to develop new gene-targeted drugs.

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Section: Discussionsupporting

confidence: 60%

Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma

et al. 2022

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“…LDHA [ 41 ] and GLUT1 [ 42 ] both display upregulation in NSCLC than normal tissues, which enable to independently predict undesirable clinical outcomes. LDHA activation may enhance the growth of NSCLC [ 43 ], and miR-449a weakens LDHA-independent glycolysis to strengthen the sensitivity of NSCLC cells to ionizing radiotherapy [ 44 ]. NSCLC growth and radiotherapy resistance depend upon GLUT1-independent glucose uptake in tumor-associated neutrophils [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming

Zhang

Tang

Cao

et al. 2022

Evidence-Based Complementary and Alternative Medicine

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Objective. Salvianolic acid B (Sal B) has been demonstrated to be a potential chemoprevention agent for several cancers. Herein, we investigated the pharmacological function of Sal B on non-small-cell lung cancer (NSCLC) metastasis. Methods. Two NSCLC cell lines (NCI-H2030 and NCI-H1650) were disposed of by 200 μM Sal B or 10 μM PKM2 agonist TEPP-46. Wound healing and transwell experiments were implemented for analyzing migratory and invasive capacities. Epithelial-to-mesenchymal transition (EMT) markers β-catenin and E-cadherin were measured via western blotting. Cellular bioenergetics were evaluated with glucose uptake, lactate production, enolase activity, cellular ATP levels, as well as seahorse-based oxygen consumption rate (OCR), extracellular acidification rate (ECAR) analysis. Metabolic reprogramming markers PKM2, LDHA, and GLUT1 were detected via western blotting and immunofluorescence. Results. The results showed that Sal B disposal weakened the migration and invasion of NCI-H2030 and NCI-H1650 cells and inactivated the EMT process according to downregulation of β-catenin and upregulation of E-cadherin. Sal B-treated NSCLC cells displayed decreased glucose uptake, lactate production, enolase activity, cellular ATP levels, OCR, and ECAR, indicating a reduction in metabolic reprogramming. Additionally, Sal B downregulated the expression of PKM2, LDHA, and GLUT1. TEPP-46 may reverse the inhibitory effect of Sal B on metastasis as well as metabolic reprogramming. Conclusion. Our findings provide evidence that Sal B enables to weaken NSCLC metastasis through PKM2-independent metabolic reprogramming, which sheds light on the promising therapeutic usage of Sal B in treating NSCLC.

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“…LDHA is a member of lactate dehydrogenase, which catalyzes pyruvate to lactate during aerobic glycolysis [21]. Evidence suggests that LDHA participates in fatty acid synthesis [22]. Overexpression of LDHA has been established in a number of malignancies, including hepatocellular carcinoma [23], breast cancer [24], and gastric cancer [25].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the fatty acid metabolism-related genes in lung adenocarcinoma to guide clinical therapy

et al. 2022

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Background Lung adenocarcinoma (LUAD) is a common cancer with a bad prognosis. Numerous investigations have indicated that the metabolism of fatty acids plays an important role in the occurrence, progression, and treatment of cancer. Consequently, the objective of the current investigation was to elucidate the role and prognostic significance of genes associated with fatty acid metabolism in patients diagnosed with LUAD. Materials and methods The data files were acquired from The Cancer Genome Atlas database and GSE31210 dataset. Univariate Cox and least absolute shrinkage and selection operator regression analyses were conducted to establish a prognostic risk scoring model depending on fatty acid metabolism-associated genes to predict the prognosis of patients with LUAD. pRRophetic algorithm was utilized to evaluate the potential therapeutic agents. Gene set variation analysis combined with cell-type identification based on the estimation of relative subsets of RNA transcript and single-sample gene set enrichment analysis was used to determine the association between immune cell infiltration and risk score. Tumor immune dysfunction and exclusion algorithm was employed to predict immunotherapeutic sensitivity. Results To forecast the prognosis of patients with LUAD, a risk scoring model based on five genes associated with fatty acid metabolism was developed, including LDHA, ALDOA, CYP4B1, DPEP2, and HPGDS. Using the risk score algorithm, patients were divided into higher- and lower-risk categories. Patients classified as minimal risk showed superior prognosis than those with elevated risk. In addition, individuals in the higher-risk group had a proclivity toward chemoresistance and amenable to immunotherapy. Conclusion The prognostic risk scoring model aids in estimating the prognosis of LUAD patients. It may also provide new insights into LUAD carcinogenesis and therapeutic strategies.

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Hippocalcin-like 1 is a key regulator of LDHA activation that promotes the growth of non-small cell lung carcinoma

Cited by 9 publications

References 35 publications

Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma

Characterization of Fatty Acid Metabolism in Lung Adenocarcinoma

Salvianolic Acid B Suppresses Non-Small-Cell Lung Cancer Metastasis through PKM2-Independent Metabolic Reprogramming

Characterization of the fatty acid metabolism-related genes in lung adenocarcinoma to guide clinical therapy

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