scholarly journals High-Throughput Screen of Natural Compounds and Biomarkers for NSCLC Treatment by Differential Expression and Weighted Gene Coexpression Network Analysis (WGCNA)

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Ling Kui ◽  
Min Li ◽  
Xiaonan Yang ◽  
Ling Yang ◽  
Qinghua Kong ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Differential Expression ◽  
High Throughput ◽  
Target Genes ◽  
Nsclc Cell Line ◽  
Nf Kappa B ◽  
Therapeutic Drugs ◽  
Lung Malignancies ◽  
Pathway Analyses ◽  
Cancer Diagnosis And Therapy

Lung cancer is known as the leading cause which presents the highest fatality rate worldwide; non-small-cell lung cancer (NSCLC) is the most prevalent type of lung carcinoma with high severity and affects 80% of patients with lung malignancies. Up to now, the general treatment for NSCLC includes surgery, chemotherapy, and radiotherapy; however, some therapeutic drugs and approaches could cause side effects and weaken the immune system. The combination of conventional therapies and traditional Chinese medicine (TCM) significantly improves treatment efficacy in lung cancer. Therefore, it is necessary to investigate the chemical composition and underlying antitumor mechanisms of TCM, so as to get a better understanding of the potential natural ingredient for lung cancer treatment. In this study, we selected 78 TCM to treat NSCLC cell line (A549) and obtained 92 transcriptome data; differential expression and WGCNA were applied to screen the potential natural ingredient and target genes. The sample which was treated with A. pierreana generated the most significant DEG set, including 6130 DEGs, 2479 upregulated, and 3651 downregulated. KEGG pathway analyses found that four pathways (MAPK, NF-kappa B, p53, and TGF-beta signaling pathway) were significantly enriched; 16 genes were significantly regulated in these four pathways. Interestingly, some of them such as EGFR, DUSP4, IL1R1, IL1B, MDM2, CDKNIA, and IDs have been used as the target biomarkers for cancer diagnosis and therapy. In addition, classified samples into 14 groups based on their pharmaceutical effects, WGCNA was used to identify 27 modules. Among them, green and darkgrey were the most relevant modules. Eight genes in the green module and four in darkgrey were identified as hub genes. In conclusion, we screened out three new TCM (B. fruticose, A. pierreana, and S. scandens) that have the potential to develop natural anticancer drugs and obtained the therapeutic targets for NSCLC therapy. Our study provides unique insights to screen the natural components for NSCLC therapy using high-throughput transcriptome analysis.

scholarly journals Urinary exosomal long noncoding RNAs serve as biomarkers for early detection of non-small cell lung cancer

2021 ◽  
Author(s):  
Quan Lin ◽  
Danli Xie ◽  
Liangliang Pan ◽  
Yongliang Lou ◽  
Mengru Shi
Keyword(s):  
Lung Cancer ◽  
Tumor Cell ◽  
Small Cell Lung Cancer ◽  
Differential Expression ◽  
Kegg Pathway ◽  
Small Cell ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Pathway Analyses ◽  
Nsclc Patients

Objective: Increasing the efficiency of early diagnosis using noninvasive biomarkers is crucial for enhancing the survival rate of lung cancer patients. We explore the differential expression of non-small cell lung cancer (NSCLC) related lncRNAs in urinary exosomes in NSCLC patients and normal controls to diagnose lung cancer. Methods: A differential expression analysis between NSCLC patients and healthy controls was performed using microarrays. Gene ontology (GO) term and Kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were used to predict potential functions of lncRNAs in NSCLC. QT-PCR was used to verify microarray results. Results: A total of 640 lncRNAs (70 up- and 570 down-regulated) were differentially expressed in NSCLC patients in comparison to healthy controls. Six lncRNAs were detected by QT-PCR. GO term and KEGG pathway analyses showed that differential lncRNAs were enriched in cellular component organization or biogenesis, as well as other biological processes and signaling pathways, such as the PI3K-AKT, FOXO, p53, and fatty acid biosynthesis. Conclusions: The differential lncRNAs in urinary exosomes are potential diagnostic biomarkers of NSCLC. The lncRNAs enriched in specific pathways may be associated with tumor cell proliferation, tumor cell apoptosis, and the cell cycle involved in the pathogenesis of NSCLC.

scholarly journals Differential expression of microRNAs and their target genes in non-small-cell lung cancer

2014 ◽  
Vol 11 (3) ◽  
pp. 2034-2040 ◽  
Author(s):  
HUI-YOUNG LEE ◽  
SEON-SOOK HAN ◽  
HWANSEOK RHEE ◽  
JUNG HOON PARK ◽  
JAE SEUNG LEE ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Differential Expression ◽  
Cell Lung Cancer ◽  
Target Genes ◽  
Small Cell ◽  
Small Cell Lung

scholarly journals Differential Expression of Micrornas and Their Target Genes in Non-Small-Cell Lung Cancer

2014 ◽  
Vol 25 ◽  
pp. iv553
Author(s):  
H. Lee ◽  
S. Han ◽  
S. Song ◽  
K. Lim ◽  
W.J. Kim
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Differential Expression ◽  
Cell Lung Cancer ◽  
Target Genes ◽  
Small Cell ◽  
Small Cell Lung

NF-κB-Induced Upregulation of miR-548as-3p Increases Invasion of NSCLC by Targeting PTEN

2019 ◽  
Vol 19 (8) ◽  
pp. 1058-1068 ◽  
Author(s):  
Sakir Akgun ◽  
Hakan Kucuksayan ◽  
Osman N. Ozes ◽  
Ozge Can ◽  
Arsenal S. Alikanoglu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Tumor Suppressor ◽  
Target Genes ◽  
Metastatic Tumor ◽  
Luciferase Reporter ◽  
Nsclc Cell Line ◽  
Cancer Type ◽  
Luciferase Reporter Gene ◽  
Tissue Samples ◽  
Qrt Pcr

Background:Non-Small Cell Lung Cancer (NSCLC) is an aggressive cancer type due to high metastatic capacity. Nuclear Factor Kappa B (NF-κB) is a consistently active transcription factor in malignant lung cancer cells and has crucial significance in NSCLC progression. It is also implicated in the transcriptional regulation of many genes including microRNAs (miRNAs) that function as tumor suppressor or oncogene. It has been increasingly reported that several miRNAs defined as gene members are induced by NF-κB. The present study aimed to find novel miRNAs that are regulated by NF-κB.Methods:Chromatin İmmunoprecipitation Sequencing (ChIP-Seq) experiment and bioinformatic analysis were used to determine NF-κB-dependent miRNAs. Western blot analysis, quantitative real-time polymerase chain reaction (qRT-PCR), luciferase reporter gene assays were carried out to investigate the target genes of miRNAs. To determine biologic activity, transwell invasion and MTT assay were carried out on H1299 NSCLC cell line. miRNA expression level was evaluated in metastatic and non-metastatic tissue samples of NSCLC patients.Results:ChIP-Seq and qRT-PCR experiments showed that miR-548as-3p is transcriptionally regulated by NF- κB in response to Tumor Necrosis Factor-α (TNF-α) treatment. Then, we found that tumor suppressor Phosphatase and Tension homolog (PTEN) is a direct target of miR-548as-3p. Furthermore, miR-548as-3p mediates phosphatidylinositol-3-OH kinase (PI3K)/Akt pathway and NF-κB-implicated genes including Matrix Metalloproteinases 9 (MMP9), Slug and Zeb1. We further showed that miR-548as-3p increased invasiveness of NSCLC cells and was upregulated in metastatic tumor tissues compared to non-metastatic ones.Conclusion:All these findings provide a miRNAs-mediated novel mechanism for NF-κB signaling and that miR-548as-3p could be a biomarker for NSCLC metastasis.

scholarly journals Novel Insights into the Potential Diagnostic Value of Circulating Exosomal IncRNA-Related Networks in Large Artery Atherosclerotic Stroke

2021 ◽  
Vol 8 ◽  
Author(s):  
Shuai Zhang ◽  
Jing Wang ◽  
Mei Jie Qu ◽  
Kun Wang ◽  
Ai Jun Ma ◽  
...  
Keyword(s):  
Differential Expression ◽  
High Throughput Sequencing ◽  
Target Genes ◽  
Expression Profiles ◽  
Diagnostic Value ◽  
Diagnostic Tools ◽  
Large Artery ◽  
Qrt Pcr ◽  
Validation Set ◽  
Pathway Analyses

Exosomes show diagnostic and therapeutic promise as carriers of ncRNAs in diseases. LncRNAs in exosomes have been identified as being stable and avoided degradation by nucleolytic enzymes. Although lncRNAs have been confirmed to be important in cancers, no studies for exo-lncRNAs have been reported in LAA stroke. High-throughput sequencing was performed to detect the differential expression profiles of lncRNAs in five paired plasma-derived exosome samples from patients with LAA stroke and controls (matched on vascular risk factors). Exo-lncRNA-associated networks were predicted with a combination of multiple databases. The expression of the selected genes in the networks was confirmed by qRT-PCR in a validation set (LAA vs. controls = 30:30). Furthermore, ROC analysis was used to evaluate the diagnostic performance of the lncRNA-related networks. A total of 1,020 differentially expressed lncRNAs were identified in LAA stroke patients. GO and KEGG pathway analyses indicated that their target genes are involved in atherosclerosis-related pathways, including inflammation, cell adhesion, and cell migration. qRT-PCR confirmed that the expression trend of differential expressed genes was consistent with RNA-seq. Furthermore, the AUCs of the lnc_002015-related network and lnc_001350-related network were 0.959 and 0.97, respectively, in LAA stroke. Our study showed the differential expression of lncRNAs in plasma exosomes and presented related diagnostic networks for LAA stroke for the first time. The results suggested that exosomal lncRNA-related networks could be potential diagnostic tools in LAA stroke.

scholarly journals Abnormal expression of rno_circRNA_014900 and rno_circRNA_005442 induced by ketamine in the rat hippocampus

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Jing Mao ◽  
Tianmei Li ◽  
Di Fan ◽  
Hongli Zhou ◽  
Jianguo Feng ◽  
...  
Keyword(s):  
Target Genes ◽  
Circular Rna ◽  
Fold Change ◽  
Rat Hippocampus ◽  
Antidepressant Effect ◽  
Signal Pathways ◽  
Qrt Pcr ◽  
Abnormal Expression ◽  
Reverse Transcription Pcr ◽  
Pathway Analyses

Abstract Background Recent studies have shown that circular RNA (circRNA) is rich in microRNA (miRNA) binding sites. We have previously demonstrated that the antidepressant effect of ketamine is related to the abnormal expression of various miRNAs in the brain. This study determined the expression profile of circRNAs in the hippocampus of rats treated with ketamine. Methods The aberrantly expressed circRNAs in rat hippocampus after ketamine injection were analyzed by microarray chip, and we further validated these circRNAs by quantitative reverse-transcription PCR (qRT-PCR). The target genes of the different circRNAs were predicted using bioinformatic analyses, and the functions and signal pathways of these target genes were investigated by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Results Microarray analysis showed that five circRNAs were aberrantly expressed in rat hippocampus after ketamine injection (fold change > 2.0, p < 0.05). The results from the qRT-PCR showed that one of the circRNAs was significantly increased (rno_circRNA_014900; fold change = 2.37; p = 0.03), while one was significantly reduced (rno_circRNA_005442; fold change = 0.37; p = 0.01). We discovered a significant enrichment in several GO terms and pathways associated with depression. Conclusion Our findings showed the abnormal expression of ketamine-induced hippocampal circRNAs in rats.

scholarly journals EGFR-ERK induced activation of GRHL1 promotes cell cycle progression by up-regulating cell cycle related genes in lung cancer

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Yiming He ◽  
Mingxi Gan ◽  
Yanan Wang ◽  
Tong Huang ◽  
Jianbin Wang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Potential Role ◽  
Target Genes ◽  
Nuclear Translocation ◽  
Phosphorylation Site ◽  
Promoter Regions ◽  
Cycle Progression

AbstractGrainyhead-like 1 (GRHL1) is a transcription factor involved in embryonic development. However, little is known about the biological functions of GRHL1 in cancer. In this study, we found that GRHL1 was upregulated in non-small cell lung cancer (NSCLC) and correlated with poor survival of patients. GRHL1 overexpression promoted the proliferation of NSCLC cells and knocking down GRHL1 inhibited the proliferation. RNA sequencing showed that a series of cell cycle-related genes were altered when knocking down GRHL1. We further demonstrated that GRHL1 could regulate the expression of cell cycle-related genes by binding to the promoter regions and increasing the transcription of the target genes. Besides, we also found that EGF stimulation could activate GRHL1 and promoted its nuclear translocation. We identified the key phosphorylation site at Ser76 on GRHL1 that is regulated by the EGFR-ERK axis. Taken together, these findings elucidate a new function of GRHL1 on regulating the cell cycle progression and point out the potential role of GRHL1 as a drug target in NSCLC.

scholarly journals Tin Mesoporphyrin Selectively Reduces Non-Small-Cell Lung Cancer Cell Line A549 Proliferation by Interfering with Heme Oxygenase and Glutathione Systems

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 917
Author(s):  
Valeria Sorrenti ◽  
Agata Grazia D’Amico ◽  
Ignazio Barbagallo ◽  
Valeria Consoli ◽  
Salvo Grosso ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Line ◽  
Heme Oxygenase ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Nsclc Cell ◽  
Antioxidant Systems ◽  
Nsclc Cell Line ◽  
Small Cell Lung

In order to maintain redox homeostasis, non-small-cell lung cancer (NSCLC) increases the activation of many antioxidant systems, including the heme-oxygenase (HO) system. The overexpression of HO-1 has been often associated with chemoresistance and tumor aggressiveness. Our results clearly showed an overexpression of the HO-1 protein in A549 NSCLC cell lines compared to that in non-cancerous cells. Thus, we hypothesized that “off-label” use of tin mesoporphyrin, a well-known HO activity inhibitor clinically used for neonatal hyperbilirubinemia, has potential use as an anti-cancer agent. The pharmacological inhibition of HO activity caused a reduction in cell proliferation and migration of A549. SnMP treatment caused an increase in oxidative stress, as demonstrated by the upregulation of reactive oxygen species (ROS) and the depletion of glutathione (GSH) content. To support these data, Western blot analysis was performed to analyze glucose-6-phosphate dehydrogenase (G6PD), TP53-induced glycolysis and the apoptosis regulator (TIGAR), and the glutamate cysteine ligase catalytic (GCLC) subunit, as they represent the main regulators of the pentose phosphate pathway (PPP) and glutathione synthesis, respectively. NCI-H292, a subtype of the NSCLC cell line, did not respond to SnMP treatment, possibly due to low basal levels of HO-1, suggesting a cellular-dependent antitumorigenic effect. Altogether, our results suggest HO activity inhibition may represent a potential target for selective chemotherapy in lung cancer subtypes.

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