Hypoxia Induced High Expression of Thioredoxin Interacting Protein (TXNIP) in Non-small Cell Lung Cancer and its Prognostic Effect

Li, Yan; Miao, Liyun; Xiao, Yonglong; Huang, Mei; Yu, Min; Meng, Kun; Cai, Hourong

doi:10.7314/apjcp.2015.16.7.2953

Cited by 23 publications

(18 citation statements)

References 26 publications

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“…In addition, it has been reported that patients with high TXNIP expression demonstrated a significantly shorter progression-free survival compared with those with low TXNIP expression (31). The expression of TXNIP could also be affected by many factors including tumour environment (31). In the present study, no obvious change in thioredoxin expression was observed in response to D-allose.…”

Section: Discussioncontrasting

confidence: 43%

“…In high-grade tumours, thioredoxin expression is diminished, suggesting loss of redox regulation in tumours with low differentiation (14). In addition, it has been reported that patients with high TXNIP expression demonstrated a significantly shorter progression-free survival compared with those with low TXNIP expression (31). The expression of TXNIP could also be affected by many factors including tumour environment (31).…”

Section: Discussionmentioning

confidence: 99%

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Additive antitumour effect of D‑allose in combination with cisplatin in non-small cell lung cancer cells

et al. 2018

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D‑allose is a rare sugar which has been shown to have growth inhibitory effects in several kinds of malignancies. However, the effect of D‑allose on lung cancer progression has not been previously studied. To investigate the antitumour effect of D‑allose in lung cancer cells and its mechanism, human non-small cell lung cancer (NSCLC) cell lines (squamous cell carcinomas: EBC1 and VMRC‑LCD; adenocarcinomas: A549, HI1017, RERF‑LC‑A1 and NCI-H1975) were treated with D‑allose (50 mM) with or without cisplatin (5 µM). D‑allose inhibited cell growth, particularly in EBC1 and VMRC‑LCD cells. In combination with cisplatin, D‑allose had a synergistic growth inhibitory effect. D‑allose increased the expression of thioredoxin interacting protein (TXNIP) at mRNA and protein levels. D‑allose decreased the proportion of cells in G1 phase and increased those in S and G2/M phases. For in vivo experiments, EBC1 cells were inoculated into BALB/c-nu mice. After tumourigenesis, D‑allose and cisplatin were injected. In this mouse xenograft model, additional treatment with D‑allose showed a significantly greater tumour inhibitory effect compared with cisplatin alone, accompanied by lower Ki‑67 and higher TXNIP expression. In conclusion, D‑allose inhibited NSCLC cell proliferation in vitro and tumour progression in vivo. In combination with cisplatin, D‑allose had an additional antitumour effect. Specifically, increased TXNIP expression and subsequent G2/M arrest play a role in D‑allose-mediated antitumour effects in NSCLC.

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Section: Discussioncontrasting

confidence: 43%

Section: Discussionmentioning

confidence: 99%

Additive antitumour effect of D‑allose in combination with cisplatin in non-small cell lung cancer cells

et al. 2018

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“…No difference in splice variants, isoforms, or gene fusion were observed between the two culture conditions. Among the differentially expressed genes, we identified genes previously shown to be regulated by hypoxia, such as BNIP3 [ 26 ], SPAG4 [ 27 , 28 ], TRF2 [ 29 ] and TXNIP [ 30 ]. When genes were clustered based on biological functions, the differentially expressed genes identified were found to be involved in biological processes that are important to certain cell therapies such as: (1) chondrogenesis and cartilage metabolism; (2) inflammation and immunomodulation; (3) cellular survival, migration and proliferation; and (4) vasculogenesis and angiogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…Therefore, expanding hBMMSCs under hypoxia in vitro rather than in atmospheric oxygen partial pressure conditions seems very intuitive and it has been proven beneficial [ 7 , 71 ]. Some of the genes identified herein have previously been described to be regulated by hypoxia, such as BNIP3 [ 26 ], SPAG4 [ 27 , 28 ], TRF2 [ 29 ] and TXNIP [ 30 ]. Stratifin (SFN) was identified for the first time as being regulated by hypoxia in hBMMSCs with a sixfold upregulation in hypoxic conditions versus atmospheric culture conditions.…”

Section: Discussionmentioning

confidence: 99%

Comparing atmospheric and hypoxic cultured mesenchymal stem cell transcriptome: implication for stem cell therapies targeting intervertebral discs

Elabd¹,

Ichim

Miller³

et al. 2018

J Transl Med

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BackgroundMesenchymal stem cells (MSCs) represent an attractive avenue for cellular therapies targeting degenerative diseases. MSC in vitro expansion is required in order to obtain therapeutic numbers during the manufacturing process. It is known that culture conditions impact cellular properties and behavior after in vivo transplantation. In this study, we aimed at evaluating the benefit of hypoxic culturing of human bone marrow derived mesenchymal stem cells on cell fitness and whole genome expression and discussed its implication on cellular therapies targeting orthopedic diseases such as chronic lower back pain.MethodsHuman bone marrow mesenchymal stem cells (hBMMSCs) were isolated from fresh human anticoagulated whole bone marrow and were cultured side by side in atmospheric (20% O2) and hypoxic (5% O2) oxygen partial pressure for up to 3 passages. Stem cell fitness was assessed by clonogenic assay, cell surface marker expression and differentiation potential. Whole genome expression was performed by mRNA sequencing. Data from clonogenic assays, cell surface marker by flow cytometry and gene expression by quantitative PCR were analyzed by two-tailed paired Student’s t-test. Data from mRNA sequencing were aligned to hg19 using Tophat-2.0.13 and analyzed using Cufflinks-2.1.1.ResultsHypoxic culturing of hBMMSCs had positive effects on cell fitness, as evidenced by an increased clonogenicity and improved differentiation potential towards adipocyte and chondrocyte lineages. No difference in osteoblast differentiation or in cell surface markers were observed. Only a small subset of genes (34) were identified by mRNA sequencing to be significantly dysregulated by hypoxia. When clustered by biological function, these genes were associated with chondrogenesis and cartilage metabolism, inflammation and immunomodulation, cellular survival, migration and proliferation, vasculogenesis and angiogenesis.ConclusionsHypoxic culturing positively impacted hBMMSCs fitness and transcriptome, potentially improving inherent properties of these cells that are critical for the development of successful cellular therapies. Hypoxic culturing should be considered for the in vitro expansion of hBMMSCs during manufacturing of cellular therapies targeting orthopedic disorders such as lower back pain.

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“…Yan Li and other researchers have found that hypoxia is a key feature in the tumor microenvironment. Under hypoxic conditions, the level of TXNIP in NSCLC tissues is upregulated, and high expression levels of TXNIP may be a poor prognostic indicator (114). It has been shown that using tyrosine kinase inhibitor (TKIs) to inhibit PI3K/Akt signaling in NSCLC cell lines can lead to a decrease in cell membranelocalized GLUT1, but increases in TXNIP expression in lung cancer tissues (98).…”

Section: Cancers Of the Respiratory System And Others (Table 3) Txnipmentioning

confidence: 99%

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

et al. 2020

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Thioredoxin-interacting protein (TXNIP) is a thioredoxin-binding protein that can mediate oxidative stress, inhibit cell proliferation, and induce apoptosis by inhibiting the function of the thioredoxin system. TXNIP is important because of its wide range of functions in cardiovascular diseases, neurodegenerative diseases, cancer, diabetes, and other diseases. Increasing evidence has shown that TXNIP expression is low in tumors and that it may act as a tumor suppressor in various cancer types such as hepatocarcinoma, breast cancer, and lung cancer. TXNIP is known to inhibit the proliferation of breast cancer cells by affecting metabolic reprogramming and can affect the invasion and migration of breast cancer cells through the TXNIP-HIF1α-TWIST signaling axis. TXNIP can also prevent the occurrence of bladder cancer by inhibiting the activation of ERK, which inhibits apoptosis in bladder cancer cells. In this review, we find that TXNIP can be regulated by binding to transcription factors or other binding proteins and can also be downregulated by epigenetic changes or miRNA. In addition, we also summarize emerging insights on TXNIP expression and its functional role in different kinds of cancers, as well as clarify its participation in metabolic reprogramming and oxidative stress in cancer cells, wherein it acts as a putative tumor suppressor gene to inhibit the proliferation, invasion, and migration of different tumor cells as well as promote apoptosis in these cells. TXNIP may therefore be of basic and clinical significance for finding novel molecular targets that can facilitate the diagnosis and treatment of malignant tumors.

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Hypoxia Induced High Expression of Thioredoxin Interacting Protein (TXNIP) in Non-small Cell Lung Cancer and its Prognostic Effect

Cited by 23 publications

References 26 publications

Additive antitumour effect of D‑allose in combination with cisplatin in non-small cell lung cancer cells

Additive antitumour effect of D‑allose in combination with cisplatin in non-small cell lung cancer cells

Comparing atmospheric and hypoxic cultured mesenchymal stem cell transcriptome: implication for stem cell therapies targeting intervertebral discs

Research Progress of TXNIP as a Tumor Suppressor Gene Participating in the Metabolic Reprogramming and Oxidative Stress of Cancer Cells in Various Cancers

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