Correlations of mRNA Levels among Efflux Transporters, Transcriptional Regulators, and Scaffold Proteins in Non-Small-Cell Lung Cancer

Multidrug resistance (MDR) due to enhanced drug efflux activity of tumor cells can severely impact the efficacy of antitumor therapies. We recently showed that increased activity of the efflux transporter P-glycoprotein (P-gp) associated with activation of Snail transcriptional regulators may be mediated mainly by moesin in lung cancer cells. Here, we aimed to systematically evaluate the relationships among mRNA expression levels of efflux transporters (P-gp, breast cancer resistance protein (BCRP), and multidrug resistance-associated protein 2 (MRP2)), scaffold proteins (ezrin (Ezr), radixin (Rdx), and moesin (Msn); ERM proteins), and SNAI family members (Snail, Slug, and Smac) in clinical lung cancer and noncancer samples. We found high correlations between relative (cancer/noncancer) mRNA expression levels of Snail and Msn, Msn and P-gp, Slug and MRP2, and Smuc and BCRP. These findings support our previous conclusion that Snail regulates P-gp activity via Msn and further suggest that Slug and Smuc may contribute to the functional regulation of MRP2 and BCRP, respectively, in lung cancer cells. This trial is registered with UMIN000023923.

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Human papillomavirus16 E6 but not E7 upregulates GLUT1 expression in lung cancer cells by upregulating thioredoxin expression

Technology in Cancer Research & Treatment ◽

10.1177/15330338211067111 ◽

2021 ◽

Vol 20 ◽

pp. 153303382110671

Author(s):

Zi-Yu Gao ◽

Na-Jin Gu ◽

Ming-Zhe Wu ◽

Shi-Yu Wang ◽

Hong-Tao Xu ◽

...

Keyword(s):

Lung Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Cell Lines ◽

Lung Cancer Cells ◽

Expression Levels ◽

Glut1 Protein ◽

Glut1 Expression ◽

E6 And E7 ◽

Mrna Expression Levels

Background and objective: E6 and E7 proteins in human papillomavirus (HPV) 16 are major oncogenes in several types of tumors, including lung cancer. Previous studies have demonstrated that both E6 and E7 oncoproteins can upregulate GLUT1 protein and mRNA expression levels in lung cancer cells. Thus, the present study aimed to investigate the main differences in the molecular mechanisms of GLUT1 expression regulated by E6 and E7. Methods: The double directional genetic manipulation and immunofluorescence were performed to explore the molecular mechanism of E6 or E7 upregulating the expression of GLUT1 in H1299 and A549 cell lines. Results: The overexpression of E6 in well-established lung cancer cell lines upregulated thioredoxin (Trx) protein expression. Notably, plasmid transfection or small interfering RNA transfection with E7 had no regulatory effect on Trx expression. As an important disulfide reductase of the intracellular antioxidant system, Trx plays important role in maintaining oxidative stress balance and protecting cells from oxidative damage. The overexpression of Trx increased the activation of NF-κB by upregulating p65 expression and promoting p65 nuclear translocation, and further upregulated GLUT1 protein and mRNA expression levels. The results of the present study demonstrated that E6, but not E7, upregulated GLUT1 expression in lung cancer cells by activating NF-κB due to the participation of Trx. Conclusion: These results suggest that Trx plays an important role in the pathogenesis of HPV-associated lung cancer, and propose a novel therapeutic target for HPV-associated lung cancer.

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Usefulness of Technetium-99m MIBI SPECT in reflecting P-glycoprotein (Pgp) or multidrug resistance-associated protein (MRP) mRNA expression levels in clinical lung cancer

Lung Cancer ◽

10.1016/s0169-5002(00)80874-0 ◽

2000 ◽

Vol 29 (1) ◽

pp. 254-255

Author(s):

T Aratani ◽

T Komori ◽

K Sueyoshi ◽

I Narabayasi

Keyword(s):

Lung Cancer ◽

Multidrug Resistance ◽

Mrna Expression ◽

Expression Levels ◽

Technetium 99M ◽

P Glycoprotein ◽

Mibi Spect ◽

Mrna Expression Levels

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Effect of Cytostatic Drugs on the mRNA Expression Levels of Ribonuclease κ in Breast and Ovarian Cancer Cells

Anti-Cancer Agents in Medicinal Chemistry ◽

10.2174/18715206113139990090 ◽

2014 ◽

Vol 14 (3) ◽

pp. 400-408 ◽

Cited By ~ 3

Author(s):

Asimina Gkratsou ◽

Emmanuel Fragoulis ◽

Diamantis Sideris

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Ovarian Cancer Cells ◽

Cytostatic Drugs ◽

Breast And Ovarian Cancer ◽

Expression Levels ◽

Mrna Expression Levels

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Comprehensive analysis of inhibitor of differentiation/DNA-binding gene family in lung cancer using bioinformatics methods

Bioscience Reports ◽

10.1042/bsr20193075 ◽

2020 ◽

Vol 40 (2) ◽

Cited By ~ 2

Author(s):

Suming Xu ◽

Yaoqin Wang ◽

Yanhong Li ◽

Lei Zhang ◽

Chunfang Wang ◽

...

Keyword(s):

Lung Cancer ◽

Transcription Factor ◽

Dna Binding ◽

Mrna Expression ◽

Family Members ◽

Enrichment Analysis ◽

Functional Enrichment ◽

Genetic Mutations ◽

Expression Levels ◽

Mrna Expression Levels

Abstract The inhibitor of differentiation/DNA-binding (ID) is a member of the helix–loop–helix (HLH) transcription factor family, and plays a role in tumorigenesis, invasiveness and angiogenesis. The aims were to investigate the expression patterns and prognostic values of individual ID family members in lung cancer, and the potential functional roles. The expression levels of ID family were assessed using the Oncomine online database and GEPIA database. Furthermore, the prognostic value of ID family members was evaluated using the Kaplan–Meier plotter database. The genetic mutations of ID family members were investigated using the cBioPortal database. Moreover, enrichment analysis was performed using STRING database and Funrich software. It was found that all the ID family members were significantly down-regulated in lung cancer. Prognostic results indicated that low mRNA expression levels of ID1 or increased mRNA expression levels of ID2/3/4 were associated with improved overall survival, first progression and post progression survival. Additionally, genetic mutations of ID family members were identified in lung cancer, and it was suggested that amplification and deep deletion were the main mutation types. Furthermore, functional enrichment analysis results suggested that ID1/2/4 were significantly enriched in ‘regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism’ for biological process, ‘transcription factor activity’ for molecular function and ‘HLH domain’ for protein domain. However, it was found that ID3 was not enriched in the above functions. The aberrant expression of ID family members may affect the occurrence and prognosis of lung cancer, and may be related to cell metabolism and transcriptional regulation.

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Proteins Associated with Cisplatin Resistance in Ovarian Cancer Cells Identified by Quantitative Proteomic Technology and Integrated with mRNA Expression Levels

Molecular & Cellular Proteomics ◽

10.1074/mcp.m500140-mcp200 ◽

2005 ◽

Vol 5 (3) ◽

pp. 433-443 ◽

Cited By ~ 95

Author(s):

Jennifer J. Stewart ◽

James T. White ◽

Xiaowei Yan ◽

Steven Collins ◽

Charles W. Drescher ◽

...

Keyword(s):

Ovarian Cancer ◽

Mrna Expression ◽

Cancer Cells ◽

Cisplatin Resistance ◽

Ovarian Cancer Cells ◽

Expression Levels ◽

Proteomic Technology ◽

Mrna Expression Levels

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M3814, a DNA-PK Inhibitor, Modulates ABCG2-Mediated Multidrug Resistance in Lung Cancer Cells

Frontiers in Oncology ◽

10.3389/fonc.2020.00674 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 3

Author(s):

Zhuo-Xun Wu ◽

Zheng Peng ◽

Yuqi Yang ◽

Jing-Quan Wang ◽

Qiu-Xu Teng ◽

...

Keyword(s):

Lung Cancer ◽

Multidrug Resistance ◽

Cancer Cells ◽

Lung Cancer Cells

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HPV16 E6/E7 upregulate hTERC mRNA and gene amplification levels by relieving the effect of LKB1 on Sp1 phosphorylation in lung cancer cells

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920917562 ◽

2020 ◽

Vol 12 ◽

pp. 175883592091756

Author(s):

Jing-Hua Yang ◽

Ming-Zhe Wu ◽

Xu-Bo Wang ◽

Shiyu Wang ◽

Xue-Shan Qiu ◽

...

Keyword(s):

Lung Cancer ◽

Mrna Expression ◽

Gene Amplification ◽

Genetic Manipulation ◽

Mrna Levels ◽

Promoter Regions ◽

Hpv16 E6 ◽

Expression Levels ◽

Malignant Group ◽

Mrna Expression Levels

Background: There is an immediate need for research on the mechanism underlying telomerase activation and overexpression. Materials & Methods: A total of 174 patients with lung cancer ( n = 106) and benign lung disease ( n = 68) were recruited for the current study. The mRNA expression levels of E6, E7, LKB1, Sp1, and hTERC in brushing cells were detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR), and hTERC amplification was also detected by fluorescence in situ hybridization (FISH). To investigate the potential mechanism, bidirectional genetic manipulation was performed in well-established lung cancer cell lines. Results: Our results indicated that the mRNA expression levels of E6, E7, Sp1, and hTERC and the amplification level of hTERC were significantly increased in the malignant group compared with those of the benign group ( p < 0.01). Conversely, the mRNA expression level of LKB1 was significantly decreased in the malignant group ( p < 0.01). The correlation between E6, E7, Sp1, and hTERC expression was positive but was negative with LKB1 ( p < 0.01). Our results also showed that HPV16 E6/E7 downregulated the expression of LKB1 at both the protein and mRNA levels. The loss of LKB1 upregulated Sp1 expression, and also promoted Sp1 activity. Sp1 further upregulated hTERC at the mRNA and gene amplification levels. Thus, we proposed a HPV–LKB1–Sp1–hTERC axis of E6/E7 upregulation of hTERC expression. Conclusion: We demonstrated for the first time that E6 and E7 promoted hTERC mRNA expression and the amplification of hTERC by relieving the effect of LKB1 on the phosphorylation of Sp1. Sp1 further activated hTERC by directly binding to the promoter regions of hTERC.

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