Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Chai, Fangyu; Zhang, Jingfang; Fu, Tao; Jiang, Peng; Huang, Yi‐Chuan; Wang, Lin; Shu, Yan; Yan, Xudong; Yu, Longgang; Xu, Zhen; Wang, Ruohuang; Xu, Bingqing; Du, Xiaoyun; Jiang, Yan; Zhang, Jisheng

doi:10.1080/19336950.2023.2208928

Cited by 8 publications

(5 citation statements)

References 64 publications

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“…Previous studies have shown that GLUT3 is considered a transcriptional target of ZEB1, playing a significant role in lung cancer when tumour cells lose their epithelial features and become more aggressive, promoting lung cancer metastasis [ 14 ]. At the same time, some studies have found that GLUT3 may significantly affect the progression of head and neck squamous cell carcinoma and colorectal cancer cells by regulating EMT [ 18 , 27 ]. Our previous experiment found that GLUT3 was enhanced in the alveolar macrophages of patients with COPD.…”

Section: Discussionmentioning

confidence: 99%

GLUT3-mediated cigarette smoke-induced epithelial-mesenchymal transition in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway

Ding,

Wang,

Zhang

et al. 2024

Respir Res

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Background Airway remodelling plays an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Epithelial–mesenchymal transition (EMT) is a significant process during the occurrence of airway remodelling. Increasing evidence suggests that glucose transporter 3 (GLUT3) is involved in the epithelial mesenchymal transition (EMT) process of various diseases. However, the role of GLUT3 in EMT in the airway epithelial cells of COPD patients remains unclear. Methods We detected the levels of GLUT3 in the peripheral lung tissue of COPD patients and cigarette smoke (CS)-exposed mice. Two Gene Expression Omnibus GEO datasets were utilised to analyse GLUT3 gene expression profiles in COPD. Western blot and immunofluorescence were used to detect GLUT3 expression. In addition, we used the AAV9-GLUT3 inhibitor to reduce GLUT3 expression in the mice model. Masson’s staining and lung function measurement were used detect the collagen deposition and penh in the mice. A cell study was performed to confirm the regulatory effect of GLUT3. Inhibition of GLUT3 expression with siRNA, Western blot, and immunofluorescence were used to detect the expression of E-cadherin, N-cadherin, vimentin, p65, and ZEB1. Results Based on the GEO data set analysis, GLUT3 expression in COPD patients was higher than in non-smokers. Moreover, GLUT3 was highly expressed in COPD patients, CS exposed mice, and BEAS-2B cells treated with CS extract (CSE). Further research revealed that down-regulation of GLUT3 significantly alleviated airway remodelling in vivo and in vitro. Lung function measurement showed that GLUT3 reduction reduced airway resistance in experimental COPD mice. Mechanistically, our study showed that reduction of GLUT3 inhibited CSE-induced EMT by down-regulating the NF-κB/ZEB1 pathway. Conclusion We demonstrate that CS enhances the expression of GLUT3 in COPD and further confirm that GLUT3 may regulate airway remodelling in COPD through the NF-κB/ZEB1 pathway; these findings have potential value in the diagnosis and treatment of COPD. The down-regulation of GLUT3 significantly alleviated airway remodelling and reduced airway resistance in vivo. Our observations uncover a key role of GLUT3 in modulating airway remodelling and shed light on the development of GLUT3-targeted therapeutics for COPD.

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Section: Discussionmentioning

confidence: 99%

GLUT3-mediated cigarette smoke-induced epithelial-mesenchymal transition in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway

Ding,

Wang,

Zhang

et al. 2024

Respir Res

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“…Six genes were not all characterized in cancer. The prognostic predictive potential of SLC2A3 for HNSCC has been reported, and this molecule also mediates cancer cell proliferation and, migration, and immune responses 36 . EFNB2 was identified as a tumor promoter in HNSCC that maximized tumor size and vascular normalization when knocked down in cancer cells and blood vessels 37 .…”

Section: Discussionmentioning

confidence: 99%

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

Yang,

Yang

et al. 2024

Sci Rep

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With the emergence of targeted inhibition strategies for Hedgehog signaling in cancer, multiple Hedgehog signaling pathway-related biomarkers have become the focus of research. SsGSEA algorithm was employed to analyze the Hedgehog pathway scores of samples in TCGA-HNSC dataset and divide them into two groups. Weighted co-expression network analysis was performed to identify modules strongly associated with the Hedgehog pathway. Differentially up-regulated genes in tumor samples in comparison to the normal ones were screened by Limma, in which genes belonging to modules strongly related to Hedgehog pathway were further filtered by LASSO reduction and multivariate Cox regression analysis to develop a model. ESTIMATE and CIBERSORT were served to characterize the tumor microenvironment (TME). TIDE assessed immunotherapy response. Hedgehog pathway activity was significantly higher in head and neck squamous cell carcinoma (HNSCC) tissues than in normal tissues and was correlated with HNSCC survival, glycan, cofactors and vitamins, drug metabolism, and matrix scores. Six genes (SLC2A3, EFNB2, OAF, COX4I2, MT2A and TXNRD1) were captured to form a Hedgehog associated 6-gene signature, and the resulting risk score was an independent indicator of HNSCC prognosis. It was significantly positively correlated with stromal score, metabolism, angiogenesis and inflammatory response. Patients in low-risk group with a low TIDE score had higher immunotherapy sensitivity relative to those in high-risk group. This study revealed novel findings of the Hedgehog pathway in HNSCC progression and opened up a Hedgehog pathology-related signature to help identify risk factors contributing to HNSCC progression and help predict immunotherapy outcomes.

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“…It is known that Ki-67 is expressed in invasive squamous cell carcinoma tissues, and its expression is closely related to cancer cell proliferation, and also positively correlated with cervical cancer stage [12]. Lee et al [13] reported that p63 promotes the development of normal epithelium and maintains its function, which is of great significance in controlling the consistency of stem cells. It is preferentially expressed in nucleus of cervical reserve cells.…”

Section: Discussionmentioning

confidence: 99%

Effect of trichostatin A on biological characteristics of side population cells of cervical cancer cell line (HeLa)

Yang,

Zhang,

Xian

et al. 2023

Trop. J. Pharm Res

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Purpose: To investigate the effect of trichostatin A (TSA) on biological characteristics of side population (SP) cells of cervical cancer cell line (HeLa)Methods: Side population (SP) and NSP cells were obtained from 6th generation of primary cervical cancer cells and cervical cancer cell line (HeLa). Cell surface markers (ATP-binding membrane transporter superfamily G member 2 (ABCG2), CD133, CD43, p63, Ki67, multidrug resistance (MDR) as well as cell cycle phase distribution and apoptosis, were determined. SP cells in HeLa were divided into 3 groups that received TSA at doses of 0.01, 0.05, and 0.2 μM. Untreated cells served as control. Cell growth inhibition rates of different dose groups were compared. SP cells in HeLa were divided into simple irradiation group and combined irradiation group TSA (10 % inhibition concentration (IC10) + irradiation, and values of SP cell survival fraction (SF) of the two groups under different irradiation conditions were compared.Results: The content of SP in HeLa cell line was significantly higher than in cervical cancer tissue (p > 0.05). There were no significant differences in expression levels of ABCG2, CD133, CD43, p63, Ki67, and MDR, as well as G0/G1, S, and G2/M phase distributions and apoptosis rate between HeLa cell line and cervical cancer tissue (p > 0.05). On the 3rd, 5th, and 7th day, SF value of SP cells was significantly higher in NSP cells (p > 0.05). With increasing concentration of TSA, SF value of NSP cells gradually decreased, while that of SP cells did not change significantly.Conclusion: Cervical cancer cell line (HeLa) contains SP cells which have biological characteristics of tumor stem cells. Moreover, TSA exerts good cytotoxicity and radio-sensitization effect on SP cells.

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Identification of SLC2A3 as a prognostic indicator correlated with the NF-κB/EMT axis and immune response in head and neck squamous cell carcinoma

Cited by 8 publications

References 64 publications

GLUT3-mediated cigarette smoke-induced epithelial-mesenchymal transition in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway

GLUT3-mediated cigarette smoke-induced epithelial-mesenchymal transition in chronic obstructive pulmonary disease through the NF-kB/ZEB1 pathway

Elucidating Hedgehog pathway's role in HNSCC progression: insights from a 6-gene signature

Effect of trichostatin A on biological characteristics of side population cells of cervical cancer cell line (HeLa)

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