JNK Signaling Pathway Suppresses LPS-Mediated Apoptosis of HK-2 Cells by Upregulating NGAL

Objective. To explore the role of the c-Jun N-terminal kinase (JNK) signaling pathway in upregulated NGAL expression and its antiapoptotic mechanism in lipopolysaccharide (LPS)-mediated renal tubular epithelial cell injury. Methods. In vitro, HK-2 cells were divided into five groups (Con, LPS 1 h, LPS 3 h, LPS 6 h, and LPS 12 h groups) based on the time of LPS (10 μM) treatment. NGAL and caspase-3 gene expression levels were detected by RT-PCR to assess dynamic changes. HK-2 cells were pretreated with SP600125 (20 μM) for 2 hours, followed by LPS (10 μM) stimulation for 3 hours. NGAL and caspase-3 gene expression levels were then determined. Results. NGAL mRNA was increased significantly within 6 hours, and caspase-3 mRNA was increased within 3 hours after treatment (P<0.05). Correlation analysis showed a high correlation between their expression (r = 0.448, P<0.05). After pretreatment with SP600125, mRNA expression of NGAL in the LPS group was inhibited, while that of caspase-3 was increased significantly. The NGAL mRNA expression level in the SB + LPS group was decreased significantly compared with that in the LPS group, but it was slightly higher than that in the SP group (∼1.5 times of that in the Con group). However, caspase-3 mRNA expression was increased significantly in the SB + LPS group (P<0.001) (3.5 times of that in the Con group). It also showed a significant increase compared with SP and LPS groups (P<0.001 vs. SB group; P<0.05 vs. LPS group). We also found that NGAL and caspase 3 proteins were increased significantly in LPS and SP + LPS groups, but SP600125 decreased the NGAL level by almost 35% and increased the caspase 3 level by 50% in the SP + LPS group compared with the LPS group (P<0.05). Conclusions. The JNK signaling pathway inhibits LPS-mediated apoptosis of renal tubular epithelial cells by upregulating NGAL.

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Correlation of messenger RNA expression patterns of ERCC1, TS, EGFR, and VEGFR2 with KRAS and BRAF mutational status in advanced colorectal cancer: Implications for targeted therapies.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.383 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 383-383

Author(s):

Martin K. H. Maus ◽

Craig Stephens ◽

Stephanie H. Astrow ◽

Peter Philipp Grimminger ◽

Dongyun Yang ◽

...

Keyword(s):

Gene Expression ◽

Colorectal Cancer ◽

Mrna Expression ◽

Advanced Colorectal Cancer ◽

Expression Patterns ◽

Mrna Levels ◽

Expression Levels ◽

Mutational Status ◽

Mrna Expression Levels ◽

Gene Expression Levels

383 Background: Gene expression levels of ERCC1, TS, EGFR and VEGFR2 may have predictive value for the personalized use of standard chemotherapeutics as well as agents targeting the EGFR and VEGF pathways and the efficacy of EGFR directed monoclonal antibodies like panitumumab and cetuximab has been confirmed to be dependent on wt KRAS and wt BRAF in patients with advanced colorectal cancer. We investigated the correlations between KRAS/BRAF mutational status and the mRNA expression levels of these genes. Methods: Formalin-fixed paraffin-embedded tumor specimens from 600 patients with advanced colorectal adenocarcinoma were microdissected and DNA and RNA was extracted. Specifically designed primers and probes were used to detect 7 different base substitutions in codon 12 and 13 of KRAS, V600E mutations in BRAF and the expression levels of ERCC1, TS, EGFR and VEGFR2 by RT-PCR. Results: Mt KRAS tumors had significantly lower TS and EGFR gene expression levels compared with wt KRAS (p<0,001), whereas mt BRAF tumors showed significantly increased TS and EGFR mRNA levels compared to wt BRAF (p<0,001). Mt BRAF tumors showed significantly higher mRNA levels than mt KRAS tumors (p<0,001). ERCC1 and VEGFR2 mRNA levels were significantly down-regulated in mt KRAS specimen (p<0,001), but showed no significant correlation with BRAF mutational status. Conclusions: KRAS and BRAF mutations are associated with opposite mRNA expression levels for TS and EGFR. Recently, resistance to BRAF inhibition in mt BRAF colorectal tumors has been shown in preclinical models to be associated with up-regulation of EGFR. Our data suggests that BRAF mutants are associated with high EGFR levels at the time of diagnosis, and not necessarily part of an acquired mechanism of resistance. Significantly lower mRNA expression levels of VEGFR2 in mt KRAS tumors may explain lower response to angiogenesis inhibition seen in the TML study.

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miRNA-206 Regulates EVI1 Gene Expression, Akt Signaling Pathway and Cell Biological Behavior in Gastric Cancer Cells

Journal of Biomaterials and Tissue Engineering ◽

10.1166/jbt.2019.2163 ◽

2019 ◽

Vol 9 (10) ◽

pp. 1381-1387

Author(s):

Wanjun Jia ◽

Yabin Zhang ◽

Ruian Wang

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Cell Proliferation ◽

Targeted Therapy ◽

Cancer Cells ◽

Signaling Pathway ◽

Biological Behavior ◽

Gastric Cancer Cells ◽

Jnk Signaling ◽

Jnk Signaling Pathway

To investigate the impact of miRNA-206 on the transcriptional expression of EVI1 gene and activation of Akt/JNK signaling pathway in gastric cancer cells, and to provide a new idea for gene-targeted therapy of gastric cancer. The miRNA-206 transfection experiment was firstly used to verify the regulation of EVI1. The experiment was divided into three groups: miRNA-206 mimics (100 nM), miRNA-206 inhibitor (100 nM), miR-NC (100 nM), and transfected into gastric cancer cells sgc7901, Western blot. EVI1 protein expression was detected; then the signal transduction and biological behavior of the cells were verified by miRNA-206 lentiviral vector transfection experiments. The experiment was divided into three groups: pLB-miRNA-206 group, empty vector group and control group (sgc7901 cell group). miRNA-206 and EVI1 mRNA levels were detected by real-time fluorescence quantitative (RT-PCR), and p-Akt and p-JNK were detected by Western blot. Protein expression, cell proliferation was quantified by MTT assay, and the alteration of cell cycle were detected by flow cytometry. miRNA-206 may affect the cell proliferation and division cycle by targeting the regulation of EVI1 transcriptional gene expression and activation of Akt/JNK signaling pathway in gastric cancer cells, and it is expected to provide an important selection site for gene-targeted therapy of gastric cancer.

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Downregulated LRRK2 gene expression inhibits proliferation and migration while promoting the apoptosis of thyroid cancer cells by inhibiting activation of the JNK signaling pathway

International Journal of Oncology ◽

10.3892/ijo.2019.4816 ◽

2019 ◽

Cited By ~ 1

Author(s):

Zheng‑Cai Jiang ◽

Xiao‑Jun Chen ◽

Qi Zhou ◽

Xiao‑Hua Gong ◽

Xiong Chen ◽

...

Keyword(s):

Gene Expression ◽

Thyroid Cancer ◽

Cancer Cells ◽

Signaling Pathway ◽

Jnk Signaling ◽

Lrrk2 Gene ◽

Jnk Signaling Pathway ◽

And Migration ◽

Thyroid Cancer Cells ◽

Proliferation And Migration

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Transcriptomic Analysis Suggests Genes Expressed Stage-Independently and Stage–Dependently Modulating the Wing Dimorphism of the Brown Planthopper

Genes ◽

10.3390/genes11010019 ◽

2019 ◽

Vol 11 (1) ◽

pp. 19 ◽

Cited By ~ 1

Author(s):

Chao Zhang ◽

Xiang-Dong Liu

Keyword(s):

Gene Expression ◽

Signaling Pathway ◽

Brown Planthopper ◽

Adherens Junction ◽

Sugar Metabolism ◽

Differentially Expressed ◽

Wing Dimorphism ◽

Expression Levels ◽

Three Stages ◽

Gene Expression Levels

Wing dimorphism is considered as an adaptive trait of insects. Brown planthoppers (BPHs) Nilaparvata lugens, a serious pest of rice, are either macropterous or brachypterous. Genetic and environmental factors are both likely to control wing morph determination in BPHs, but the hereditary law and genes network are still unknown. Here, we investigated changes in gene expression levels between macropterous and brachypterous BPHs by creating artificially bred morphotype lines. The nearly pure-bred strains of macropterous and brachypterous BPHs were established, and their transcriptomes and gene expression levels were compared. Over ten-thousand differentially expressed genes (DEGs) between macropterous and brachypterous strains were found in the egg, nymph, and adult stages, and the three stages shared 6523 DEGs. The regulation of actin cytoskeleton, focal adhesion, tight junction, and adherens junction pathways were consistently enriched with DEGs across the three stages, whereas insulin signaling pathway, metabolic pathways, vascular smooth muscle contraction, platelet activation, oxytocin signaling pathway, sugar metabolism, and glycolysis/gluconeogenesis were significantly enriched by DEGs in a specific stage. Gene expression trend profiles across three stages were different between the two strains. Eggs, nymphs, and adults from the macropterous strain were distinguishable from the brachypterous based on gene expression levels, and genes that were related to wing morphs were differentially expressed between wing strains or strain × stage. A proposed mode based on genes and environments to modulate the wing dimorphism of BPHs was provided.

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Epidermal growth factor receptor (EGFR) mRNA expression levels are strongly correlated between primary colorectal cancer and corresponding liver metastases

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.4106 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 4106-4106

Author(s):

H. Kuramochi ◽

K. Hayashi ◽

K. Uchida ◽

M. Yamamoto ◽

K. D. Danenberg ◽

...

Keyword(s):

Gene Expression ◽

Liver Metastases ◽

Mrna Expression ◽

Growth Factor Receptor ◽

Primary Cancer ◽

Egfr Gene ◽

Expression Levels ◽

Epidermal Growth ◽

Mrna Expression Levels ◽

Gene Expression Levels

4106 Background: As it has been well known that epidermal growth factor receptor (EGFR) is strongly related to a tumor proliferation and a metastasis, new EGFR-inhibitory small molecules, such as gefitinib and erlotinib, and EGFR antibodies have been developed recently. It is reported that the high expression levels of EGFR mRNA are associated with high response probability and longer progression-free survival in gefitinib-treated lung cancer patients. Thus, since liver metastases are the main cause of death for most of colorectal cancer (CRC) patients, it is reasonable to expect that measurement of EGFR gene expression levels in liver metastases would provide the best prediction of therapy benefit, but in most cases, only biopsies of the patient’s primary tumor are readily available for analysis. Our aim was to determine how EGFR gene expression levels in primary CRC were related to those in liver metastases. Methods: Thirty-one pairs of primary CRC and corresponding liver metastases were analyzed. (18 males and 13 females: Median age 66 (range 45–85)). Formalin-fixed, paraffin-embedded tumor specimens were dissected by using laser-captured microdissection. RNA was extracted and cDNA was prepared by reverse-transcription. Quantitation of target gene and internal reference gene was performed using real-time PCR (Taqman PCR). Results: No significant difference was seen between median mRNA expression levels of EGFR in primary cancer and those in corresponding liver metastases (Median value: 1.35 vs 1.24, p=0.99 , Wilcoxon signed rank test), although the median value of EGFR mRNA from normal liver tissue is significantly higher than those from normal colon mucosa (Median value: 5.06 vs 1.39, p<0.0001). When matched tissue sets were compared on an individual basis, there was a significant correlation for EGFR mRNA expression between primary cancer and corresponding liver metastases (rs=0.78, p<0.0001, Spearman rank correlation coefficient). Conclusions: A good prediction of EGFR mRNA levels in liver metastases can be obtained by measuring those of primary CRC. No significant financial relationships to disclose.

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L-Arginine protects mouse Leydig cells against T-2 toxin-induced apoptosis in vitro

Toxicology and Industrial Health ◽

10.1177/0748233720964312 ◽

2020 ◽

Vol 36 (12) ◽

pp. 1031-1038

Author(s):

Yong Fa Zhang ◽

Jian Ying Yang ◽

Xiang Ping Meng ◽

Na Nie ◽

Mei Cui Tang ◽

...

Keyword(s):

Gene Expression ◽

Leydig Cells ◽

Caspase 3 ◽

Cultured Cells ◽

Mitochondrial Activity ◽

Protective Mechanism ◽

Expression Levels ◽

Induced Apoptosis ◽

Gene Expression Levels

To explore the protective mechanism of L-arginine against T-2 toxin-induced apoptosis in mouse Leydig cells, we investigated whether L-arginine can prevent T-2 toxin-induced apoptosis in mouse Leydig cells and explored the underlying mechanisms. Leydig cells were isolated and cultured with control, T-2 toxin (10 nM), L-arginine (0.25, 0.5, and 1.0 mM), and T-2 toxin (10 nM T-2 toxin) + L-arginine (0.25, 0.5, or 1.0 mM) for 24 h. Cells and supernatants were harvested to examine proliferation of the cells, the apoptosis rate, activity of caspase-3 and mitochondria, and the gene expression levels of Bcl-2, Bax, PARP, and caspase-3. Results showed that proliferation and mitochondrial activity of Leydig cells were inhibited by administration of T-2 toxin. Bcl-2 gene expression levels was decreased, while the gene expression levels of Bax and PARP were increased, which could trigger mitochondria-mediated apoptosis, activate downstream caspase-3, and then increased caspase-3 at both activity and gene expression levels. The expression of the Bcl-2 gene was upregulated and the expression of Bax, caspase-3, and PARP gene were downregulated when L-arginine was added to the cultured cells. The results of this study showed that L-arginine could block T-2 toxin-induced apoptosis in mouse Leydig cells by regulating specific intracellular death-related pathways.

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