scholarly journals Expression, Prognosis and Gene Regulation Network of NFAT Transcription Factors in Non-Small Cell Lung Cancer

2021 ◽  
Vol 27 ◽  
Author(s):  
Jin Ma ◽  
Rao Du ◽  
Yan Huang ◽  
Wen Zhong ◽  
Huan Gui ◽  
...  

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. The nuclear factor of activated T cells (NFAT) family is implicated in tumorigenesis and progression in various types of cancer. However, little is known about their expression patterns, distinct prognostic values, and potential regulatory networks in NSCLC. In this study, we comprehensively analyzed the distinct expression and prognostic value of NFATs in NSCLC through various large databases, including the Oncomine, UCSC Xena Browser, UALCAN databases, Kaplan–Meier Plotter, cBioPortal, and Enrichr. In lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), NFAT1/2/4/5 mRNA expression levels were significantly decreased and NFAT3 mRNA expression level was significantly increased. The cBioPortal database analysis showed that the mRNA dysregulation was one of the single most important factors for NFAT alteration in LUAD and LUSC and that both LUAD and LUSC cases with the alterations in the mRNA expression of NFATs had significantly better overall survival (OS). High expression levels of NFAT1/2/4/5 were significantly associated with better OS in LUAD, whereas high NFAT3 expression led to a worse OS. Overexpression of NFAT1/2 predicted better OS in LUSC, whereas high NFAT5 expression led to a worse OS. The networks for NFATs and the 50 most frequently altered neighbor genes in LUAD and LUSC were also constructed. NFATs and genes significantly associated with NFAT mRNA expression in LUAD and LUSC were significantly enriched in the cGMP-dependent protein kinase and Wnt signaling pathways. These results showed that the NFAT family members displayed varying degrees of abnormal expressions, suggesting that NFATs may be therapeutic targets for patients with NSCLC. Aberrant expression of NFATs was found to be associated with OS in the patients with NSCLC; among NFATs, NFAT3/4 may be new biomarkers for the prognosis of LUAD. However, further studies are required to validate our findings.

2010 ◽  
Vol 28 (4) ◽  
pp. 1411-1417 ◽  
Author(s):  
Chunxia Su ◽  
Songwen Zhou ◽  
Ling Zhang ◽  
Shengxiang Ren ◽  
Jianfang Xu ◽  
...  

2009 ◽  
Vol 2009 ◽  
pp. 1-6 ◽  
Author(s):  
Jana Rolff ◽  
Cornelia Dorn ◽  
Johannes Merk ◽  
Iduna Fichtner

Tumor cells that are nonsensitive to anticancer drugs frequently have a multidrug resistant (MDR) phenotype. Many studies with cell lines and patient material have been done to investigate the impact of different resistance markers at protein and mRNA level in drug resistance but with contradictory outcome. In the present study, 26 well-characterised patient-derived non-small cell lung cancer xenografts were used. The known chemosensitivity to etoposide, carboplatin, gemcitabine, paclitaxel and erlotinib was compared to the protein and mRNA expression of BCRP, LRP, MDR1, and MRP1. Further, four of these xenografts were short-term treated to analyse possible regulation mechanisms after therapeutic interventions. We found a borderline correlation between thebcrpmRNA expression and the response of xenografts to etoposide. All other constitutive mRNA and protein expression levels were not correlated to any drug response and were not significantly influenced by a short term treatment. The present results indicate that the expression levels of MDR proteins and mRNA investigated do not play an important role in the chemoresistance of NSCLC in the in vivo situation.


2009 ◽  
Vol 10 (1) ◽  
pp. 47-52 ◽  
Author(s):  
Roberta Bartolucci ◽  
Jia Wei ◽  
Jose Javier Sanchez ◽  
Laia Perez-Roca ◽  
Imane Chaib ◽  
...  

2019 ◽  
Vol 51 (2) ◽  
pp. 176-184
Author(s):  
Sener Tasdemir ◽  
◽  
Serpil Taheri ◽  
Hilal Akalin ◽  
Olgun Kontas ◽  
...  

2020 ◽  
Vol 20 (17) ◽  
pp. 2074-2081
Author(s):  
Onur Tokgun ◽  
Pervin E. Tokgun ◽  
Kubilay Inci ◽  
Hakan Akca

Background: Small Cell Lung Cancer (SCLC) is a highly aggressive malignancy. MYC family oncogenes are amplified and overexpressed in 20% of SCLCs, showing that MYC oncogenes and MYC regulated genes are strong candidates as therapeutic targets for SCLC. c-MYC plays a fundamental role in cancer stem cell properties and malignant transformation. Several targets have been identified by the activation/repression of MYC. Deregulated expression levels of lncRNAs have also been observed in many cancers. Objective: The aim of the present study is to investigate the lncRNA profiles which depend on MYC expression levels in SCLC. Methods: Firstly, we constructed lentiviral vectors for MYC overexpression/inhibition. MYC expression is suppressed by lentiviral shRNA vector in MYC amplified H82 and N417 cells, and overexpressed by lentiviral inducible overexpression vector in MYC non-amplified H345 cells. LncRNA cDNA is transcribed from total RNA samples, and 91 lncRNAs are evaluated by qRT-PCR. Results: We observed that N417, H82 and H345 cells require MYC for their growth. Besides, MYC is not only found to regulate the expressions of genes related to invasion, stem cell properties, apoptosis and cell cycle (p21, Bcl2, cyclinD1, Sox2, Aldh1a1, and N-Cadherin), but also found to regulate lncRNAs. With this respect, expressions of AK23948, ANRIL, E2F4AS, GAS5, MEG3, H19, L1PA16, SFMBT2, ZEB2NAT, HOTAIR, Sox2OT, PVT1, and BC200 were observed to be in parallel with MYC expression, whereas expressions of Malat1, PTENP1, Neat1, UCA1, SNHG3, and SNHG6 were inversely correlated. Conclusion: Targeting MYC-regulated genes as a therapeutic strategy can be important for SCLC therapy. This study indicated the importance of identifying MYC-regulated lncRNAs and that these can be utilized to develop a therapeutic strategy for SCLC.


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