scholarly journals LncRNA CCAT1 Enhances Chemoresistance in Hepatocellular Carcinoma by Targeting QKI-5

2020 ◽  
Author(s):  
Jing Shi ◽  
Cao Guo ◽  
Junli Ma
Keyword(s):  
Hepatocellular Carcinoma ◽  
Drug Resistance ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Tumor Model ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Promising Alternative

Abstract Background: A major reason for treatment failure of cancer is acquisition of drug resistance. The specific mechanisms underlying hepatocellular carcinoma (HCC) chemoresistance need to be fully elucidated. lncRNAs involve in drug resistance in some cancers, however, the exact functions of lncRNA colon cancer-associated transcript 1 (CCAT1) in oxaliplatin resistance in HCC need to be elucidated.Methods: Functional analysis of CCAT1 on oxaliplatin sensitivity was performed in HCC cell lines HCCLM3 and HepG2, and in a subcutaneous tumor model receiving OXA treatment. Furthermore, the downstream signaling targets of CCAT1 in HCC were explored. Results: CCAT1 promoted HCC proliferation and reduced the apoptosis induced by oxaliplatin. Knockout of CCAT1 could increased chemosensitivity in vitro and in vivo. Further study found that QKI-5 was an important mediator and blocking of QKI-5/p38 MAPK signaling pathway enhanced oxaliplatin sensitivity.Conclusions: CCAT1 promoted proliferation and oxaliplatin resistance by QKI-5/p38 MAPK signaling pathway in HCC. Targeting CCAT1 in combination with chemotherapeutics may be a promising alternative to reverse drug resistance in HCC treatment.

scholarly journals Attenuation of High Glucose-Induced Damage in RPE Cells through p38 MAPK Signaling Pathway Inhibition

2021 ◽  
Vol 12 ◽  
Author(s):  
Grazia Maugeri ◽  
Claudio Bucolo ◽  
Filippo Drago ◽  
Settimio Rossi ◽  
Michelino Di Rosa ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
High Glucose ◽  
Retinal Pigment ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Rpe Cells ◽  
Cox 2

This study aimed to investigate the high glucose damage on human retinal pigment epithelial (RPE) cells, the role of p38 MAPK signaling pathway and how dimethyl fumarate can regulate that. We carried out in vitro studies on ARPE-19 cells exposed to physiological and high glucose (HG) conditions, to evaluate the effects of DMF on cell viability, apoptosis, and expression of inflammatory and angiogenic biomarkers such as COX-2, iNOS, IL-1β, and VEGF. Our data have demonstrated that DMF treatment attenuated HG-induced apoptosis, as confirmed by reduction of BAX/Bcl-2 ratio. Furthermore, in RPE cells exposed to HG we observed a significant increase of iNOS, COX-2, and IL-1β expression, that was reverted by DMF treatment. Moreover, DMF reduced the VEGF levels elicited by HG, inhibiting p38 MAPK signaling pathway. The present study demonstrated that DMF provides a remarkable protection against high glucose-induced damage in RPE cells through p38 MAPK inhibition and the subsequent down-regulation of VEGF levels, suggesting that DMF is a small molecule that represents a good candidate for diabetic retinopathy treatment and warrants further in vivo and clinical evaluation.

scholarly journals PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway

2021 ◽  
Author(s):  
Zhiqiang Han ◽  
Dongming Liu ◽  
Lu Chen ◽  
Yuchao He ◽  
Xiangdong Tian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Rna Seq ◽  
Hcc Cells

Abstract Background Some studies have reported that the activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1, as a critical ribosome has been rarely reported in human tumors. Thus, the roles of PNO1 in HCC should be explored. Methods We collected 150 formalin-fixed and paraffin-embedded (FFPE) samples and 8 fresh samples to explore the expression and prognosis of PNO1 in HCC by immunohistochemistry, Western Blotting and RT-PCR. Public databases (TCGA and GEO) were used to verify the expression and prognosis. The functions of PNO1 in HCC was verified by in vitro and in vivo experiments. The underlying molecular mechanisms of PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results PNO1 expression was considerably higher in HCC tissues and the higher expression of PNO1 was associated with poor prognosis of HCC patients. In vitro experiments indicated that PNO1 overexpression promoted proliferation and depressed apoptosis of HCC cells. In addition, high expression of PNO1 increased autophagy of HCC cells. Consistent results were also observed in vivo experiments. The results of the RNA-seq analysis indicted that PNO1 as an oncogene promoted HCC progression through the MAPK signaling pathway. The results were also verified by in vivo experiments. Conclusions PNO1 was overexpressed in HCC, promoted autophagy and inhibited apoptosis of HCC cells via the MAPK signaling pathway.

scholarly journals PNO1 regulates autophagy and apoptosis of hepatocellular carcinoma via the MAPK signaling pathway

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Zhiqiang Han ◽  
Dongming Liu ◽  
Lu Chen ◽  
Yuchao He ◽  
Xiangdong Tian ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Malignant Tumors ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Hcc Cells

AbstractSome studies have reported that activated ribosomes are positively associated with malignant tumors, especially in hepatocellular carcinoma (HCC). The RNA-binding protein PNO1 is a critical ribosome rarely reported in human tumors. This study aimed to explore the molecular mechanisms of PNO1 in HCC. Using 150 formalin-fixed and paraffin-embedded samples and 8 fresh samples, we found high PNO1 expression in HCC tumor tissues through Western blotting and RT-PCR. Moreover, the higher PNO1 expression was associated with poor HCC prognosis patients. In vitro and in vivo experiments indicated that PNO1 overexpression promoted the proliferation and depressed the apoptosis of HCC cells. High PNO1 expression also increased the autophagy of HCC cells. The molecular mechanisms underlying PNO1 were examined by RNA-seq analysis and a series of functional experiments. Results showed that PNO1 promoted HCC progression through the MAPK signaling pathway. Therefore, PNO1 was overexpressed in HCC, promoted autophagy, and inhibited the apoptosis of HCC cells through the MAPK signaling pathway.

scholarly journals An Integration of Network Pharmacology and Experimental Verification to Investigate the Mechanism of Guizhi to Treat Nephrotic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan He ◽  
Qiang Li ◽  
Guangli Du ◽  
Guofeng Meng ◽  
Jijia Sun ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Molecular Docking ◽  
Protein Expression ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Experimental Verification ◽  
Active Component ◽  
Mapk Signaling

Background: Guizhi has the pharmacological activity of anti-inflammatory. However, the effect mechanism of Guizhi against nephrotic syndrome (NS) remains unclear. A network pharmacological approach with experimental verification in vitro and in vivo was performed to investigate the potential mechanisms of Guizhi to treat NS.Methods: Active compounds and potential targets of Guizhi, as well as the related targets of NS were obtained from the public databases. The intersecting targets of Guizhi and NS were obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI), genes ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. And the overall network was constructed with Cytoscape. Molecular docking verification was carried out by AutoDock Vina. Finally, in vitro and in vivo experiments were performed to verify the mechanism of Guizhi to treat NS.Results: 63 intersecting targets were obtained, and the top five key targets mainly involed in NF- Kappa B and MAPK signaling pathway. In the overall network, cinnamaldehyde (CA) was the top one active compound with the highest degree value. The molecular docking showed that the top five key targets were of good binding activity with the active components of Guizhi. To in vitro experiment, CA, the main active component of Guizhi, inhibited the secretion of IL-1β, IL-6, TNF-α in LPS challenged RAW264.7 cells, and down regulated the protein expression of p-NF-κB p65 and p-p38 MAPK in LPS challenged RAW264.7 cells. In vitro experiment showed that, 24 urinary protein and renal function were increased in ADR group. To western blot, CA down regulated the protein expression of p-p38 MAPK in rats of adriamycin-induced nephropathy.Conclusion: CA might be the main active component of Guizhi to treat NS, and the underlying mechanism might mainly be achieved by inhibiting MAPK signaling pathway.

scholarly journals Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway

2020 ◽  
Vol Volume 14 ◽  
pp. 2667-2684 ◽  
Author(s):  
Xing Zhou ◽  
Xingchun Wu ◽  
Luhui Qin ◽  
Shunyu Lu ◽  
Hongliang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals Icariin Promotes the Migration of BMSCs In Vitro and In Vivo via the MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Jiao ◽  
Wang Tang ◽  
He Huang ◽  
Zhaofei Zhang ◽  
Donghua Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Signaling ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Mapk Signaling Pathway ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Actin Stress Fiber Formation

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in tissue engineering for regenerative medicine due to their multipotent differentiation potential. However, their poor migration ability limits repair effects. Icariin (ICA), a major component of the Chinese medical herb Herba Epimedii, has been reported to accelerate the proliferation, osteogenic, and chondrogenic differentiation of BMSCs. However, it remains unknown whether ICA can enhance BMSC migration, and the possible underlying mechanisms need to be elucidated. In this study, we found that ICA significantly increased the migration capacity of BMSCs, with an optimal concentration of 1 μmol/L. Moreover, we found that ICA stimulated actin stress fiber formation in BMSCs. Our work revealed that activation of the MAPK signaling pathway was required for ICA-induced migration and actin stress fiber formation. In vivo, ICA promoted the recruitment of BMSCs to the cartilage defect region. Taken together, these results show that ICA promotes BMSC migration in vivo and in vitro by inducing actin stress fiber formation via the MAPK signaling pathway. Thus, combined administration of ICA with BMSCs has great potential in cartilage defect therapy.

scholarly journals Effect of Total Flavones from Cuscuta Chinensis on Anti-Abortion via the MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-wang Wu ◽  
Yi-hui Feng ◽  
Dong-ying Wang ◽  
Wei-yu Qiu ◽  
Qing-ying Yu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Prolactin Receptor ◽  
Chinese Herb ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Dependent Manner ◽  
Active Components ◽  
Cuscuta Chinensis

For centuries, the Chinese herb Cuscuta chinensis has been applied clinically for abortion prevention in traditional Chinese medicine (TCM). Total flavones extracted from Cuscuta chinensis (TFCC) are one of the active components in the herb and also display anti-abortion effect similar to the unprocessed material. However, how TFCC exerts the anti-abortion effect remains largely unknown. In this study, we aim at characterizing the anti-abortion effects of TFCC and its underlying molecular mechanism in vitro and in vivo using human primary decidua cells and a mifepristone-induced abortion model in rat, respectively. The damage to the decidua caused by mifepristone in vivo was reversed by TFCC treatment in a dosage-dependent manner. High dosage of TFCC significantly upregulated the expression of estrogen receptor (ER), progesterone receptor (PR), and prolactin receptor (PRLR) in decidua tissue but downregulated the expression of p-ERK. Furthermore, we detected higher level of p-ERK and p-p38 in primary decidua cells from spontaneous abortion while treatment by TFCC downregulated their expression. Our results suggest TFCC mediates its anti-abortion effect by interfering with MAPK signaling pathway.

scholarly journals Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Yuan Chen ◽  
Kangquan Shou ◽  
Chunlong Gong ◽  
Huarui Yang ◽  
Yi Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Therapeutic Potential ◽  
Biological Activities ◽  
Interleukin 1 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
No Production ◽  
Surgically Induced

It has been suggested that the activation of the p38 mitogen activated protein kinases (MAPKs) signaling pathway plays a significant role in the progression of OA by leading to the overexpression of proinflammatory cytokines, chemokines, and signaling enzymes in human osteoarthritis chondrocytes. However, most p38 MAPK inhibitors applied for OA have been thought to be limited due to their potential long-term toxicities. Geniposide (GE), an iridoid glycoside purified from the fruit of the herb, has been widely used in traditional medicine for the treatment of a variety of chronic inflammatory diseases. In this study, we evaluated the inhibition effect of geniposide on the inflammatory progression of the surgically induced osteoarthritis and whether the protective effect of geniposide on OA is related to the inhibition of the p38 MAPK signaling pathway.In vitro, geniposide attenuated the expression of inflammatory cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF-α), and nitric oxide (NO) production as well as matrix metalloproteinase- (MMP-) 13 in chondrocytes isolated from surgically induced rabbit osteoarthritis model. Additionally, geniposide markedly suppressed the expression of IL-1, TNF-α, NO, and MMP-13 in the synovial fluid from the rabbits with osteoarthritis. More importantly, our results clearly demonstrated that the inhibitory effect of geniposide on surgery-induced expression of inflammatory mediators in osteoarthritis was closely associated with the suppression of the p38 MAPK signaling pathways. Our study demonstrates that geniposide may have therapeutic potential to serve as an alternative agent for the p38 MAPK inhibition for the treatment of OA due to its inherent features of biological activities and low toxicity as a traditional Chinese medicine.

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