scholarly journals Downregulation of Filamin a Expression in the Aorta Is Correlated With Aortic Dissection

2021 ◽  
Vol 8 ◽  
Author(s):  
Yue Chen ◽  
Xiang Wei ◽  
Zihao Zhang ◽  
Yi He ◽  
Bo Huo ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Gene Expression Omnibus ◽  
Cross Linking ◽  
Mrna Levels ◽  
Scaffolding Proteins ◽  
Filamin A ◽  
Cellular Functions ◽  
Expression Levels ◽  
Protein Levels ◽  
Geo Database

Filamins (FLNs) are actin cross-linking proteins, and as scaffolding proteins, FLNs are closely associated with the stabilization of the cytoskeleton. Nevertheless, the biological importance of FLNs in aortic dissection (AD) has not been well-elucidated. In this study, we first reanalyzed datasets downloaded from the Gene Expression Omnibus (GEO) database, and we found that in addition to the extracellular matrix, the actin cytoskeleton is a key structure associated with AD. Given that FLNs are involved in remodeling the cytoskeleton to affect cellular functions, we measured their expression levels in the aortas of patients with Stanford type A AD (TAAD). Our results showed that the mRNA and protein levels of FLNA were consistently decreased in dissected aortas of both humans and mice, while the FLNB protein level was upregulated despite decreased FLNB mRNA levels, and comparable expression levels of FLNC were observed between groups. Furthermore, the immunohistochemistry results demonstrated that FLNA was highly expressed in smooth muscle cells (SMCs) of aorta in non-AD samples, and downregulated in the medial layer of the dissected aortas of humans and mice. Moreover, we revealed that FOS and JUN, forming a dimeric transcription factor called AP-1 (activating protein-1), were positively correlated with the expression of FLNA in aorta. Either overexpression of FOS or JUN alone, or overexpression of FOS and JUN together, facilitated the expression of FLNA in primary cultured human aortic SMCs. In the present study, we not only detected the expression pattern of FLNs in aortas of humans and mice with or without AD, but we also found that the expression of FLNA in the AD samples was significantly reduced and that AP-1 might regulate the expression of FLNA. Our findings will contribute to the elucidation of the pathological mechanisms of AD and provide potential therapeutic targets for AD.

scholarly journals Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics

2021 ◽  
Vol 22 (23) ◽  
pp. 12791
Author(s):  
Alexia Grangeon ◽  
Valérie Clermont ◽  
Azemi Barama ◽  
Fleur Gaudette ◽  
Jacques Turgeon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Small Intestine ◽  
Protein Expression ◽  
Mrna Levels ◽  
Targeted Proteomics ◽  
Tissue Samples ◽  
Human Organ ◽  
Expression Levels ◽  
Protein Levels ◽  
Human Small Intestine

The human small intestine can be involved in the first-pass metabolism of drugs. Under this condition, members of the CYP450 superfamily are expected to contribute to drug presystemic biotransformation. The aim of this study was to quantify protein expression levels of 16 major CYP450 isoforms in tissue obtained from nine human organ donors in seven subsections of the small intestine, i.e., duodenum (one section, N = 7 tissue samples), jejunum (three subsections (proximal, mid and distal), N = 9 tissue samples) and ileum (three subsections, (proximal, mid and distal), N = 9 tissue samples), using liquid chromatography tandem mass spectrometry (LC-MS/MS) based targeted proteomics. CYP450 absolute protein expression levels were compared to mRNA levels and enzyme activities by using established probe drugs. Proteins corresponding to seven of sixteen potential CYP450 isoforms were detected and quantified in various sections of the small intestine: CYP2C9, CYP2C19, CYP2D6, CYP2J2, CYP3A4, CYP3A5 and CYP4F2. Wide inter-subject variability was observed, especially for CYP2D6. CYP2C9 (p = 0.004) and CYP2C19 (p = 0.005) expression levels decreased along the small intestine. From the duodenum to the ileum, CYP2J2 (p = 0.001) increased, and a trend was observed for CYP3A5 (p = 0.13). CYP3A4 expression was higher in the jejunum than in the ileum (p = 0.03), while CYP4F2 expression was lower in the duodenum compared to the jejunum and the ileum (p = 0.005). CYP450 protein levels were better correlated with specific isoform activities than with mRNA levels. This study provides new data on absolute CYP450 quantification in human small intestine that could improve physiologically based pharmacokinetic models. These data could better inform drug absorption profiles while considering the regional expression of CYP450 isoforms.

scholarly journals Correlation between Protein and mRNA Abundance in Yeast

1999 ◽  
Vol 19 (3) ◽  
pp. 1720-1730 ◽  
Author(s):  
Steven P. Gygi ◽  
Yvan Rochon ◽  
B. Robert Franza ◽  
Ruedi Aebersold
Keyword(s):  
Protein Expression ◽  
Capillary Liquid Chromatography ◽  
Metabolic Labeling ◽  
Mrna Levels ◽  
Mrna Transcript ◽  
Expression Levels ◽  
Protein Levels ◽  
Liquid Chromatography Tandem Mass ◽  
Steady State Levels ◽  
2D Gel

ABSTRACT We have determined the relationship between mRNA and protein expression levels for selected genes expressed in the yeastSaccharomyces cerevisiae growing at mid-log phase. The proteins contained in total yeast cell lysate were separated by high-resolution two-dimensional (2D) gel electrophoresis. Over 150 protein spots were excised and identified by capillary liquid chromatography-tandem mass spectrometry (LC-MS/MS). Protein spots were quantified by metabolic labeling and scintillation counting. Corresponding mRNA levels were calculated from serial analysis of gene expression (SAGE) frequency tables (V. E. Velculescu, L. Zhang, W. Zhou, J. Vogelstein, M. A. Basrai, D. E. Bassett, Jr., P. Hieter, B. Vogelstein, and K. W. Kinzler, Cell 88:243–251, 1997). We found that the correlation between mRNA and protein levels was insufficient to predict protein expression levels from quantitative mRNA data. Indeed, for some genes, while the mRNA levels were of the same value the protein levels varied by more than 20-fold. Conversely, invariant steady-state levels of certain proteins were observed with respective mRNA transcript levels that varied by as much as 30-fold. Another interesting observation is that codon bias is not a predictor of either protein or mRNA levels. Our results clearly delineate the technical boundaries of current approaches for quantitative analysis of protein expression and reveal that simple deduction from mRNA transcript analysis is insufficient.

scholarly journals Integrated bioinformatics analysis for differentially expressed genes and signaling pathways identification in gastric cancer

2019 ◽  
Author(s):  
ChenChen Yang ◽  
Aifeng Gong
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Differentially Expressed Genes ◽  
Kegg Pathway ◽  
Gene Expression Omnibus ◽  
Differentially Expressed ◽  
Mrna Levels ◽  
Pcr Assay ◽  
Microarray Datasets ◽  
Geo Database

Abstract Background Gastric cancer (GC) has a high mortality rate in cancer-related deaths worldwide. Here, we identified several vital candidate genes related to gastric cancer development and revealed the potential pathogenic mechanisms using integrated bioinformatics analysis.Methods Two microarray datasets from Gene Expression Omnibus (GEO) database integrated. Limma package was used to analyze differentially expressed genes (DEGs) between GC and matched normal specimens. DAVID was utilized to conduct Gene ontology (GO) and KEGG enrichment analysis. The relative expression of OLFM4, IGF2BP3, CLDN1and MMP1were analyzed based on TCGA database provided by UALCAN. Western blot and quantitative real time PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1and MMP1 in GC tissues and cell lines, respectively.Results We downloaded the expression profiles of GSE103236 and GSE118897 from the Gene Expression Omnibus (GEO) database. Two integrated microarray datasets were used to obtain differentially expressed genes (DEGs), and bioinformatics methods were used for in-depth analysis. After gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichments analysis, we identified 61 DEGs in common, of which the expression of 34 genes were elevated and 27 genes were decreased. GO analysis displayed that the biological functions of DEGs mainly focused on negative regulation of growth, fatty acid binding, cellular response to zinc ion and calcium-independent cell-cell adhesion. KEGG pathway analysis demonstrated that these DEGs mainly related to the Wnt and tumor signaling pathway. Interestingly, we found 4 genes were most significantly upregulated in the DEGs, which were OLFM4, IGF2BP3, CLDN1 and MMP1.Then, we confirmed the upregulation of these genes in STAD based on sample types. In the final, western blot and qRT-PCR assay were performed to determine the protein and mRNA levels of OLFM4, IGF2BP3, CLDN1 and MMP1 in GC tissues and cell lines.Conclusion In our study, using integrated bioinformatics to screen DEGs in gastric cancer could benefit us for understanding the pathogenic mechanism underlying gastric cancer progression. Meanwhile, we also identified four significantly upregulated genes in DEGs from both two datasets, which might be used as the biomarkers for early diagnosis and prevention of gastric cancer.

scholarly journals O30 A comprehensive analysis of ontogeny of renal drug transporters: mRNA analyses, quantitative proteomics and localization

2019 ◽  
Vol 104 (6) ◽  
pp. e13.2-e13
Author(s):  
KWK Cheung ◽  
BD van Groen ◽  
E Spaans ◽  
MD van Borselen ◽  
ACJM de Bruijn ◽  
...  
Keyword(s):  
Drug Transporters ◽  
Mrna Levels ◽  
Potential Conflict ◽  
Renal Handling ◽  
Expression Levels ◽  
Protein Levels ◽  
Renal Transporters ◽  
Age Related ◽  
Exogenous Compounds ◽  
Endogenous Substrates

BackgroundPostnatal developmental changes of human renal membrane transporters, which are key players of disposition of renally cleared drugs and endogenous substrates, are largely unknown. This study aimed to characterize the ontogeny of 11 human renal transporters to understand changes in the renal clearance of substrate drugs in children.Methods mRNA levels of known renal transporters: BCRP, MATE1, MATE2-K, MDR1, MRP2, MRP4, URAT1, GLUT2, OAT1, OAT3 and OCT2, and the transcription factor PXR were measured with RT-qPCR in 184 human postmortem frozen renal cortical tissues (preterm newborns - adults; 1 day-75 yrs old) from individuals of European and African descent. Protein expression of all but MRP2, MRP4 and PXR was quantified with LC-MS/MS SRM in 62 of those samples (term newborns - adults; 1 day-29 yrs old). Localization of MRP4 was tested with immunohistochemistry.ResultsExpression levels of MDR1, URAT1, OAT1, OAT3, and OCT2 increased with age, but levels of MATE1 and GLUT2 were stable from birth. Protein levels of MATE2-K and BCRP showed no difference from newborns to adults despite age-related changes in mRNA expression. MRP2, MRP4 and PXR expression levels were stable. MRP4 localization in pediatric samples was similar to that in adult samples.ConclusionRenal drug transporters exhibited different rates and patterns of maturation, suggesting that renal handling of both endogenous and exogenous compounds may change with age. It is important to consider ontogeny of renal transporters during pediatric drug development.Disclosure(s)The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Views expressed in this paper are those of authors and do not necessarily reflect the official views or policies of the FDA; nor does any mention of trade names, commercial practices, or organization imply endorsement by the U.S. Government.*Contributed equally,**Contributed equally

scholarly journals Yiqi Huoxue Recipe Improves Liver Regeneration in Rats after Partial Hepatectomy via JNK Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Wen-cong Li ◽  
Su-xian Zhao ◽  
Wei-guang Ren ◽  
Hui-juan Du ◽  
Yu-guo Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Underlying Mechanism ◽  
Mrna Levels ◽  
Protective Effects ◽  
Jnk Pathway ◽  
Expression Levels ◽  
Protein Levels ◽  
Mrna And Protein Expression

The liver is the only visceral organ that exhibits a remarkable capability of regenerating in response to partial hepatectomy (PH) or chemical injury. Improving liver regeneration (LR) ability is the basis for the favourable treatment outcome of patients after PH, which can serve as a potential indicator for postoperative survival. The present study aimed to investigate the protective effects of Yiqi Huoxue recipe (YQHX) on LR after PH in rats and further elucidate its underlying mechanism. A two-thirds PH rat model was used in this study. Wistar rats were randomly divided into four groups: sham-operated, PH, YQHX + PH, and Fuzheng Huayu decoction (FZHY) + PH groups. All rats were sacrificed under anesthesia at 24 and 72 h after surgery. The rates of LR were calculated, and the expression levels of cyclin D1 and c-jun were determined by immunohistochemical staining. The protein levels of p-JNK1/2, JNK1/2, p-c-jun, c-jun, Bax, and Bcl-2 were detected by Western blotting, while the mRNA levels of JNK1, JNK2, c-jun, Bax, and Bcl-2 were examined by real-time polymerase chain reaction (RT-PCR). At the corresponding time points, YQHX and FZHY administration dramatically induced the protein levels of p-JNK1/2 compared to the PH group p<0.05, while FZHY + PH group showed prominently increase in p-JNK1/2 protein levels compared to the YQHX + PH group p<0.05. A similar trend was observed for the expression levels of p-c-jun. Compared to the PH group, YQHX and FZHY markedly reduced the mRNA and protein expression levels of Bax at 24 h after PH, while those in the FZHY + PH group decreased more obviously p<0.05. Besides, in comparison with the PH group, YQHX and FZHY administration predominantly upregulated the mRNA and protein expression levels of Bcl-2 at 24 and 72 h after PH p<0.05. In conclusion, YQHX improves LR in rats after PH by inhibiting hepatocyte apoptosis via the JNK signaling pathway.

scholarly journals Activation of alternative NF-κB signaling during recovery of disuse-induced loss of muscle oxidative phenotype

2014 ◽  
Vol 306 (6) ◽  
pp. E615-E626 ◽  
Author(s):  
A. H. V. Remels ◽  
N. A. Pansters ◽  
H. R. Gosker ◽  
A. M. W. J. Schols ◽  
R. C. J. Langen
Keyword(s):  
Molecular Mechanisms ◽  
Myosin Heavy Chain Isoforms ◽  
Sirtuin 1 ◽  
Hindlimb Suspension ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Expression Levels ◽  
Protein Levels ◽  
Oxidative Phenotype

Physical inactivity-induced loss of skeletal muscle oxidative phenotype (OXPHEN), often observed in chronic disease, adversely affects physical functioning and quality of life. Potential therapeutic targets remain to be identified, since the molecular mechanisms involved in reloading-induced recovery of muscle OXPHEN remain incompletely understood. We hypothesized a role for alternative NF-κB, as a recently identified positive regulator of muscle OXPHEN, in reloading-induced alterations in muscle OXPHEN. Markers and regulators (including alternative NF-κB signaling) of muscle OXPHEN were investigated in gastrocnemius muscle of mice subjected to a hindlimb suspension/reloading (HLS/RL) protocol. Expression levels of oxidative phosphorylation subunits and slow myosin heavy chain isoforms I and IIA increased rapidly upon RL. After an initial decrease upon HLS, mRNA levels of peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC) molecules PGC-1α and PGC-1β and mRNA levels of mitochondrial transcription factor A (Tfam) and estrogen-related receptor α increased upon RL. PPAR-δ, nuclear respiratory factor 1 (NRF-1), NRF-2α, and sirtuin 1 mRNA levels increased during RL although expression levels were unaltered upon HLS. In addition, both Tfam and NRF-1 protein levels increased significantly during the RL period. Moreover, upon RL, IKK-α mRNA and protein levels increased, and phosphorylation of P100 and subsequent processing to P52 were elevated, reflecting alternative NF-κB activation. We conclude that RL-induced recovery of muscle OXPHEN is associated with activation of alternative NF-κB signaling.

scholarly journals Filamin A is reduced and contributes to the CASR sensitivity in human parathyroid tumors

2017 ◽  
Vol 58 (2) ◽  
pp. 91-103 ◽  
Author(s):  
Alessandra Mingione ◽  
Chiara Verdelli ◽  
Stefano Ferrero ◽  
Valentina Vaira ◽  
Vito Guarnieri ◽  
...  
Keyword(s):  
Protein Expression ◽  
Hek293 Cells ◽  
Erk Signaling ◽  
Mrna Levels ◽  
Filamin A ◽  
Expression Levels ◽  
Parathyroid Tumors ◽  
Erk Phosphorylation ◽  
Mrna And Protein Expression ◽  
Signaling Activation

Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca2+]o). [Ca2+]o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca2+]o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants.

scholarly journals Weighted Gene Co-Expression Network Analysis Identifies Specific Modules and Hub Genes Related to Hyperlipidemia

2018 ◽  
Vol 48 (3) ◽  
pp. 1151-1163 ◽  
Author(s):  
Liu Miao ◽  
Rui-Xing  Yin ◽  
Shang-Ling Pan ◽  
Shuo Yang ◽  
De-Zhai Yang ◽  
...  
Keyword(s):  
Network Analysis ◽  
Sequence Similarity ◽  
Gene Expression Omnibus ◽  
Expression Levels ◽  
Relative Expression ◽  
Protein Protein Interaction ◽  
Histone Deacetylase 4 ◽  
Complex Detection ◽  
Normal Controls ◽  
Geo Database

Background/Aims: The present study attempted to identify the potential key genes and pathways of hyperlipidemia, and to investigate the possible mechanisms associated with them. Methods: The array data of GSE3059 were downloaded, including thirteen samples of hyperlipidemia from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was performed with WGCNA package, and the salmon and midnight blue modules were found as the highest correlation. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses for these two modules were performed by cluster Profiler and DOSE package. A protein-protein interaction (PPI) network was established using Cytoscape software, and significant modules were analyzed using Molecular Complex Detection. Results: Five genes (histone deacetylase 4, HDAC4; F2R like trypsin receptor 1, F2RL1; abhydrolase domain containing 2, ABHD2; transmembrane 4 L six family member 1, TM4SF1; and family with sequence similarity 13-member A, FAM13A) were found with a significant meaning. When their expression levels were validated with RT-qPCR, the relative expression levels were lower (HDAC4) and higher (F2RL1, ABHD2, TM4SF1 and FAM13A) in hyperlipidemia than in normal controls (P < 0.05-0.01). Subgroup analysis showed that the relative expression levels of HDAC4 were lower, whereas those of F2RL1 and ABHD2 were higher in Maonan than in Han ethnic groups (P < 0.05). Conclusion: Except for genetic factors and environmental exposures, epigenetic influence was another mechanism of hyperlipidemia in our study populations, which needed to further confirm.

scholarly journals IL-6 Induced by Periodontal Inflammation Causes Neuroinflammation and Disrupts the Blood–Brain Barrier

2020 ◽  
Vol 10 (10) ◽  
pp. 679
Author(s):  
Daisuke Furutama ◽  
Shinji Matsuda ◽  
Yosuke Yamawaki ◽  
Saki Hatano ◽  
Ai Okanobu ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Gingival Tissue ◽  
Mrna Levels ◽  
Expression Levels ◽  
Protein Levels ◽  
Periodontal Inflammation ◽  
Blood Brain

Background: Periodontal disease (PD) is a risk factor for systemic diseases, including neurodegenerative diseases. The role of the local and systemic inflammation induced by PD in neuroinflammation currently remains unclear. The present study investigated the involvement of periodontal inflammation in neuroinflammation and blood–brain barrier (BBB) disruption. Methods: To induce PD in mice (c57/BL6), a ligature was placed around the second maxillary molar. Periodontal, systemic, and neuroinflammation were assessed based on the inflammatory cytokine mRNA or protein levels using qPCR and ELISA. The BBB permeability was evaluated by the mRNA levels and protein levels of tight junction-related proteins in the hippocampus using qPCR and immunofluorescence. Dextran tracing in the hippocampus was also conducted to examine the role of periodontal inflammation in BBB disruption. Results: The TNF-α, IL-1β, and IL-6 levels markedly increased in gingival tissue 1 week after ligation. The IL-6 serum levels were also increased by ligature-induced PD. In the hippocampus, the IL-1β mRNA expression levels were significantly increased by ligature-induced PD through serum IL-6. The ligature-induced PD decreased the claudin 5 expression levels in the hippocampus, and the neutralization of IL-6 restored its levels. The extravascular 3-kDa dextran levels were increased by ligature-induced PD. Conclusions: These results suggest that the periodontal inflammation-induced expression of IL-6 is related to neuroinflammation and BBB disruption in the hippocampus, ultimately leading to cognitive impairment. Periodontal therapy may protect against neurodegenerative diseases.

scholarly journals High expression level of MMP9 is associated with poor prognosis in patients with clear cell renal carcinoma

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e5050 ◽  
Author(s):  
Haitao Niu ◽  
Feng Li ◽  
Qingshui Wang ◽  
Zhoujie Ye ◽  
Qi Chen ◽  
...  
Keyword(s):  
Renal Carcinoma ◽  
Clear Cell ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Mrna Levels ◽  
Clear Cell Renal Carcinoma ◽  
Protein Levels ◽  
Mmp9 Expression ◽  
Cell Renal Carcinoma

Matrix metallopeptidase 9 (MMP9) was found to be associated with tumor aggressiveness. In this study, we focused on the correlation between MMP9 expression and clear cell renal carcinoma (ccRCC). Through the Gene Expression Omnibus (GEO) database, the Cancer Genome Atlas (TCGA) database and immunohistochemical (IHC) staining, we observed that compared with adjacent normal renal tissues, in ccRCC tissues the mRNA and protein levels of MMP9 were enhanced, and the mRNA levels of GTP-binding protein smg p21B(RAP1B), B rapidly accelerated fibrosarcoma (RAF), methyl ethyl ketone2 (MEK2), extracellular regulated protein kinases1 (ERK1), ERK2, v-ets avian erythroblastosis virus E26 oncogene homolog1 (ETS1) and ETS2 also increased. The Kaplan–Meier survival analysis suggested that high MMP9 expression was an unfavorable prognostic biomarker for ccRCC patients. Our results indicated that the increased expression level of MMP9 in ccRCC may be due to the activation of the Mitogen-activated protein kinases (MAPK)/ERK signaling pathway, and MMP9 may be an attractive target for ccRCC therapy.

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