scholarly journals Gene Regulation Network Based Analysis Associated with TGF-beta Stimulation in Lung Adenocarcinoma Cells

2017 ◽  
Vol 15 (1) ◽  
pp. 1-9
Author(s):  
Lin Hua ◽  
Hong Xia ◽  
Wei-ying Zheng ◽  
Li An
Keyword(s):  
Gene Regulation ◽  
Lung Adenocarcinoma ◽  
Tgf Beta ◽  
Gene Regulation Network ◽  
Adenocarcinoma Cells ◽  
Regulation Network ◽  
Lung Adenocarcinoma Cells

scholarly journals Expression and Gene Regulation Network of NUDT21 in Lung Adenocarcinoma and Prediction of Anticancer Components of Pinellia Ternata Based on Data Mining

2021 ◽  
Author(s):  
Yongli SITU ◽  
Li-na LONG ◽  
Hai-jian LI ◽  
Zhi-xin FANG ◽  
Hong NIE
Keyword(s):  
Gene Regulation ◽  
Dna Binding ◽  
Lung Adenocarcinoma ◽  
Prognostic Value ◽  
Regulatory Region ◽  
Expression Level ◽  
Pinellia Ternata ◽  
Gene Regulation Network ◽  
Regulation Network ◽  
Target Network

Abstract Background NUDT21 belongs to NUDT families, which is thought to play an essential role in cancer growth and progression in recent years. Abnormal NUDT21 expression is closely related to lung adenocarcinoma (LUAD). However, the expression level, gene regulation network, and prognostic value of NUDT21 in LUAD remain unclear. Besides, the active compounds of Pinellia ternata against LUAD are still not clear yet. Therefore, an in-depth study of the expression and gene regulation network of NUDT21 is of great theoretical significance and clinical demand for discovering new targets and strategies for the treatment of LUAD and the further improvement of the therapeutic effect of LUAD. Also, the targeted NUDT21 active ingredients of Pinellia ternata were sought to provide a theoretical basis for its clinical application in the treatment of LUAD. Methods A variety of online analysis tools were used in this study, including cBioPortal, ONCOMINE, GeneMANIA, GEPIA, Metascape, UALCAN, LinkedOmics, Metascape, TIMER, TRRUST, The Human Protein Atlas, TCMSP, and AutoDock Vina. Results The levels of transcription and expression of NUDT21 were significantly increased in patients with LUAD. Gene altered of NUDT21 was up to 12% in LUAD patients. However, the promoter methylation level of NUDT21 in LUAD was lower compared to normal human. LUAD patients' survival with the low expression level of NUDT21 was better prognostic value than LUAD patients with high expression level. Forty-eight nodes and 572 edges were found in the PPI network constructed with NUDT21 and its neighboring genes. Regulatory region DNA binding, transcription regulatory region DNA binding, and regulatory region nucleic acid binding were the primary function of NUDT21 and its neighboring genes. The KEGG pathway of NUDT21 and its neighboring genes were mainly involved in the apelin signaling pathway, PI3K-Akt signaling pathway, and axon guidance. Our results showed that DNMT1, HDAC1, and MYC were the critical transcription factor targets involved in the network of NUDT21 and its neighboring genes. We also found that CDK1, ATM and PLK1 were main kinase targets in the NUDT21 kinase-target network. The NUDT21 miRNA-target network was associated with MIR-302C, MIR-9, and MIR-330. Moreover, the expression of NUDT21 was positively related to the infiltration of CD8 + T cells, macrophages, neutrophils and dendritic cell. 13 active compounds of Pinellia ternata were retrieved from the TCMSP. Among them, baicalein was the best combination with NUDT21. Conclusions Our results revealed the expression and potential regulatory network of NUDT21 in LUAD, laying a foundation for further research on the role of NUDT21 in cancer. Furthermore, we offer new therapeutic targets and prognostic biomarkers for the reference. Finally, we provide potential therapeutic drugs from traditional Chinese medicine in the treatment of LUAD.

scholarly journals PFKFB4 promotes lung adenocarcinoma progression via phosphorylating and activating transcriptional coactivator SRC-2

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Jiguang Meng ◽  
Xuxin Chen ◽  
Zhihai Han
Keyword(s):  
Lung Adenocarcinoma ◽  
Transcriptional Activity ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Transcriptional Coactivator ◽  
Downstream Target ◽  
Steroid Receptor Coactivator ◽  
Adenocarcinoma Cells ◽  
Family Protein ◽  
Lung Adenocarcinoma Cells

Abstract Background To investigate the role and its potential mechanism of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) in lung adenocarcinoma. Methods Co-immunoprecipitation was performed to analyze the interaction between PFKFB4 and SRC-2. Western blot was used to investigate the phosphorylation of steroid receptor coactivator-2 (SRC-2) on the condition that PFKFB4 was knockdown. Transcriptome sequencing was performed to find the downstream target of SRC-2. Cell Counting Kit-8 (CCK-8) assay, transwell assay and transwell-matrigel assay were used to examine the proliferation, migration and invasion abilities in A549 and NCI-H1975 cells with different treatment. Results In our study we found that PFKFB4 was overexpressed in lung adenocarcinoma associated with SRC family protein and had an interaction with SRC-2. PFKFB4 could phosphorylate SRC-2 at Ser487, which altered SRC-2 transcriptional activity. Functionally, PFKFB4 promoted lung adenocarcinoma cells proliferation, migration and invasion by phosphorylating SRC-2. Furthermore, we identified that CARM1 was transcriptionally regulated by SRC-2 and involved in PFKFB4-SRC-2 axis on lung adenocarcinoma progression. Conclusions Our research reveal that PFKFB4 promotes lung adenocarcinoma cells proliferation, migration and invasion via enhancing phosphorylated SRC-2-mediated CARM1 expression.

scholarly journals PD-L1 lncRNA splice isoform promotes lung adenocarcinoma progression via enhancing c-Myc activity

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Shuang Qu ◽  
Zichen Jiao ◽  
Geng Lu ◽  
Bing Yao ◽  
Ting Wang ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Lung Adenocarcinoma ◽  
Solid Tumors ◽  
Immune Checkpoint ◽  
Checkpoint Inhibition ◽  
Immune Checkpoint Inhibition ◽  
Non Coding Rna ◽  
Adenocarcinoma Cells ◽  
Lung Adenocarcinoma Cells ◽  
Long Non Coding Rna

Abstract Background Although using a blockade of programmed death-ligand 1 (PD-L1) to enhance T cell immune responses shows great promise in tumor immunotherapy, the immune-checkpoint inhibition strategy is limited for patients with solid tumors. The mechanism and efficacy of such immune-checkpoint inhibition strategies in solid tumors remains unclear. Results Employing qRT-PCR, Sanger sequencing, and RNA BaseScope analysis, we show that human lung adenocarcinoma (LUAD) all produce a long non-coding RNA isoform of PD-L1 (PD-L1-lnc) by alternative splicing, regardless if the tumor is positive or negative for the protein PD-L1. Similar to PD-L1 mRNA, PD-L1-lnc in various lung adenocarcinoma cells is significantly upregulated by IFNγ. Both in vitro and in vivo studies demonstrate that PD-L1-lnc increases proliferation and invasion but decreases apoptosis of lung adenocarcinoma cells. Mechanistically, PD-L1-lnc promotes lung adenocarcinoma progression through directly binding to c-Myc and enhancing c-Myc transcriptional activity. Conclusions In summary, the PD-L1 gene can generate a long non-coding RNA through alternative splicing to promote lung adenocarcinoma progression by enhancing c-Myc activity. Our results argue in favor of investigating PD-L1-lnc depletion in combination with PD-L1 blockade in lung cancer therapy.

Sign in / Sign up

Export Citation Format

Share Document