miRNA-199a-5p/SLC2A1 axis regulates glucose metabolism in non-small cell lung cancer

Xu, Yikun; Chai, Binshu; Wang, Xianyi; Wu, Zong; Gu, Zhenyu; Liu, Xiaomin; Zhao, Yiqi; Chen, Tangbing; Sun, Qiangling

doi:10.7150/jca.67990

Cited by 19 publications

(12 citation statements)

References 35 publications

(30 reference statements)

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“…In our previous study, Xu et al [ 66 ] found that SLC2A1, a member of the GLUTs, was a direct target of miR-199a-5p. Down-regulation of SLC2A1 suppressed NSCLC cell proliferation, consistent with the role of miR-199a-5p.…”

Section: Resultsmentioning

confidence: 99%

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Wei

Chai

et al. 2022

IJMS

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Lung cancer is the leading cause of cancer death worldwide. miR-199a, which has two mature molecules: miR-199a-3p and miR-199a-5p, plays an important biological role in the genesis and development of tumors. We collected recent research results on lung cancer and miR-199a from Google Scholar and PubMed databases. The biological functions of miR-199a in lung cancer are reviewed in detail, and its potential roles in lung cancer diagnosis and treatment are discussed. With miR-199a as the core point and a divergence outward, the interplay between miR-199a and other ncRNAs is reviewed, and a regulatory network covering various cancers is depicted, which can help us to better understand the mechanism of cancer occurrence and provide a means for developing novel therapeutic strategies. In addition, the current methods of diagnosis and treatment of lung cancer are reviewed. Finally, a conclusion was drawn: miR-199a inhibits the development of lung cancer, especially by inhibiting the proliferation, infiltration, and migration of lung cancer cells, inhibiting tumor angiogenesis, increasing the apoptosis of lung cancer cells, and affecting the drug resistance of lung cancer cells. This review aims to provide new insights into lung cancer therapy and prevention.

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Section: Resultsmentioning

confidence: 99%

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Wei

Chai

et al. 2022

IJMS

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“…SLC2A1 encodes a glucose transporter protein, GLUT1, which plays a key role in the uptake of glucose by cells, transporting glucose from outside the cell to the inside, thereby providing raw materials for glycolysis ( Liu et al, 2022 ). The study by Xu Y. et al (2022) suggests that miRNA-199a-5p promotes the malignant progression of non-small cell lung cancer by targeting SLC2A1. SLCO4C1 encodes a member of the Organic Anion Transporting Polypeptides (OATPs) family, primarily expressed on the basolateral side of renal tubular epithelial cells, responsible for transporting substances from the cell into the blood.…”

Section: Discussionmentioning

confidence: 99%

Intratumor microbiome derived glycolysis-lactate signatures depicts immune heterogeneity in lung adenocarcinoma by integration of microbiomic, transcriptomic, proteomic and single-cell data

Deng,

Chen,

Luo

et al. 2023

Front. Microbiol.

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IntroductionMicrobiome plays roles in lung adenocarcinoma (LUAD) development and anti-tumor treatment efficacy. Aberrant glycolysis in tumor might promote lactate production that alter tumor microenvironment, affecting microbiome, cancer cells and immune cells. We aimed to construct intratumor microbiome score to predict prognosis of LUAD patients and thoroughly investigate glycolysis and lactate signature’s association with LUAD immune cell infiltration.MethodsThe Cancer Genome Atlas-LUAD (TCGA-LUAD) microbiome data was downloaded from cBioPortal and analyzed to examine its association with overall survival to create a prognostic scoring model. Gene Set Enrichment Analysis (GSEA) was used to find each group’s major mechanisms involved. Our study then investigated the glycolysis and lactate pattern in LUAD patients based on 19 genes, which were correlated with the tumor microenvironment (TME) phenotypes and immunotherapy outcomes. We developed a glycolysis-lactate risk score and signature to accurately predict TME phenotypes, prognosis, and response to immunotherapy.ResultsUsing the univariate Cox regression analysis, the abundance of 38 genera were identified with prognostic values and a lung-resident microbial score (LMS) was then developed from the TCGA-LUAD-microbiome dataset. Glycolysis hallmark pathway was significantly enriched in high-LMS group and three distinct glycolysis-lactate patterns were generated. Patients in Cluster1 exhibited unfavorable outcomes and might be insensitive to immunotherapy. Glycolysis-lactate score was constructed for predicting prognosis with high accuracy and validated in external cohorts. Gene signature was developed and this signature was elevated in epithelial cells especially in tumor mass on single-cell level. Finally, we found that the glycolysis-lactate signature levels were consistent with the malignancy of histological subtypes.DiscussionOur study demonstrated that an 18-microbe prognostic score and a 19-gene glycolysis-lactate signature for predicting prognosis of LUAD patients. Our LMS, glycolysis-lactate score and glycolysis-lactate signature have potential roles in precision therapy of LUAD patients.

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“…Downregulation of SLC2A1 can interfere with glycolysis in lung cancer cells. Thus, it can inhibit cell proliferation, migration, and the cell cycle and promote apoptosis ( 58 , 59 ). In addition, for the intersected genes of two features, tumor-secreted adrenomedullin ( ADM ) is recognized as a type of regulatory polypeptide driving both tumor and lymph node angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of a novel signature incorporating lipid metabolism and immune-related genes for assessing prognosis and immune landscape in lung adenocarcinoma

Wang

Fang

et al. 2022

Front. Immunol.

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BackgroundAs the crosstalk between metabolism and antitumor immunity continues to be unraveled, we aim to develop a prognostic gene signature that integrates lipid metabolism and immune features for patients with lung adenocarcinoma (LUAD).MethodsFirst, differentially expressed genes (DEGs) related to lipid metabolism in LUAD were detected, and subgroups of LUAD patients were identified via the unsupervised clustering method. Based on lipid metabolism and immune-related DEGs, variables were determined by the univariate Cox and LASSO regression, and a prognostic signature was established. The prognostic value of the signature was evaluated by the Kaplan–Meier method, time-dependent ROC, and univariate and multivariate analyses. Five independent GEO datasets were employed for external validation. Gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), and immune infiltration analysis were performed to investigate the underlying mechanisms. The sensitivity to common chemotherapeutic drugs was estimated based on the GDSC database. Finally, we selected PSMC1 involved in the signature, which has not been reported in LUAD, for further experimental validation.ResultsLUAD patients with different lipid metabolism patterns exhibited significant differences in overall survival and immune infiltration levels. The prognostic signature incorporated 10 genes and stratified patients into high- and low-risk groups by median value splitting. The areas under the ROC curves were 0.69 (1-year), 0.72 (3-year), 0.74 (5-year), and 0.74 (10-year). The Kaplan–Meier survival analysis revealed a significantly poorer overall survival in the high-risk group in the TCGA cohort (p < 0.001). In addition, both univariate and multivariate Cox regression analyses indicated that the prognostic model was the individual factor affecting the overall survival of LUAD patients. Through GSEA and GSVA, we found that tumor progression and inflammatory and immune-related pathways were enriched in the high-risk group. Additionally, patients with high-risk scores showed higher sensitivity to chemotherapeutic drugs. The in vitro experiments further confirmed that PSMC1 could promote the proliferation and migration of LUAD cells.ConclusionsWe developed and validated a novel signature incorporating both lipid metabolism and immune-related genes for all-stage LUAD patients. This signature can be applied not only for survival prediction but also for guiding personalized chemotherapy and immunotherapy regimens.

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miRNA-199a-5p/SLC2A1 axis regulates glucose metabolism in non-small cell lung cancer

Cited by 19 publications

References 35 publications

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

miR-199a: A Tumor Suppressor with Noncoding RNA Network and Therapeutic Candidate in Lung Cancer

Intratumor microbiome derived glycolysis-lactate signatures depicts immune heterogeneity in lung adenocarcinoma by integration of microbiomic, transcriptomic, proteomic and single-cell data

Comprehensive analysis of a novel signature incorporating lipid metabolism and immune-related genes for assessing prognosis and immune landscape in lung adenocarcinoma

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