scholarly journals LINC02085 Regulates Cell Growth and Inflammatory Response in Rheumatoid Arthritis by Regulating PI3K/ AKT Signaling Pathway

2020 ◽  
Author(s):  
Jianting Wen ◽  
Jian Liu ◽  
Xin Wang ◽  
Jie Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Growth ◽  
Inflammatory Response ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Arthritis Score ◽  
Akt Signaling Pathway ◽  
Primary Fibroblast

Abstract Background: The present study explored the possible functions and the underlying mechanism of long Non-coding RNA LINC02085 in rheumatoid arthritis (RA). Methods: Primary fibroblast-like synoviocytes (FLS) were separated from synovial tissues and was established cell lines, then cultured for subsequent cell experiments by transfecting different vectors. Rat with AA were injected with sh-LINC02085. The progression of AA was explored by measuring arthritis score and histologic analysis. ELISA analysis was employed to detect the levels of inflammatory cytokines. CCK8 assay, migration and invasion assays were used to evaluate the proliferation, migration and invasion abilities of cells, respectively. Besides, the levels of the the PI3K/AKT pathway-related proteins were measured by WB and IF. Results: The expression level of LINC02085 was significant high in patients with RA, and positively associated with clinical indexes. We found that LINC02085 was upregulated in RA -FLS and TNF-αstimulated. And overexpression of LINC02085 could promote proliferation, migration and invasion induced by TNF-α, through upregulating the levels of TNF-αand TNFAIP2 and promoting the activation of PI3K/AKT pathway. Whereas downexpression of LINC02085 received the opposite results. Knockdown of LINC02085 significantly ameliorated the progression of AA reflected by decreased arthritis score and cartilage destruction. Conclusion: The present study revealed that LINC02085 could regulate cell growth and inflammatory response of RA-FLS by activating the PI3K/ AKT signaling pathway, subsequently playing important roles in promoting the occurrence and development of RA.

scholarly journals PAR-2 promotes cell proliferation, migration, and invasion through activating PI3K/AKT signaling pathway in oral squamous cell carcinoma

2019 ◽  
Vol 39 (7) ◽  
Author(s):  
Kai-Liang Tang ◽  
Han-Ying Tang ◽  
Yi Du ◽  
Tian Tian ◽  
Shi-Jiang Xiong
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Signaling Pathway ◽  
Squamous Cell ◽  
Mrna Level ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Migration And Invasion ◽  
Akt Signaling Pathway

AbstractObjective: This research aimed to explore the function of protease activated receptor 2 (PAR-2) in oral squamous cell carcinoma (OSCC) development and progression, as well as underlying molecular mechanism.Methods: Tissue samples were collected from 115 OSCC patients. Quantitative real-time PCR (qRT-PCR) was performed to measure the expression of PAR-2 mRNA in OSCC tissues and cells. MTT and Transwell assays were used to detect the proliferation, migration, and invasion of OSCC cells, respectively. Western blot was performed to determine protein expression.Results: The expression of PAR-2 mRNA was up-regulated in OSCC tissue and cells (P<0.01), and its mRNA level was obviously correlated to tumor differentiation and TNM stage in OSCC (P<0.05 for both). The activation of PAR-2 with PAR-2AP (PAR-2 agonist) significantly promoted the proliferation, migration, and invasion of OSCC cells, while its knockout could inhibit malignant behaviors of OSCC cells (P<0.05). Excessive activation of PAR-2 enhanced phosphorylation level of PI3K, AKT, and mTOR revealing the activation of PI3K/AKT pathway. Moreover, LY294002, the inhibitor of PI3K/AKT pathway, could reverse oncogenic action caused by PAR-2 activation.Conclusion: PAR-2 can promote OSCC growth and progression via activating PI3K/AKT signaling pathway.

scholarly journals miR-499 promotes immature porcine Sertoli cell growth through the PI3K/AKT pathway by targeting the PTEN gene

Reproduction ◽  
2020 ◽  
Vol 159 (2) ◽  
pp. 145-157 ◽  
Author(s):  
Hu Gao ◽  
Bin Chen ◽  
Hui Luo ◽  
Bo Weng ◽  
Xiangwei Tang ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Signaling Pathway ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Pten Gene ◽  
Seminiferous Tubules ◽  
Akt Signaling Pathway

Sertoli cells are indispensable for normal spermatogenesis, and increasing evidence has shown that miRNAs participate in the regulation of Sertoli cell growth. However, the functions and regulatory mechanisms of miRNAs in Sertoli cells of domestic animals have not been fully investigated. In the present study, we mainly investigated the regulatory roles of miR-499 in immature porcine Sertoli cells. The results showed that miR-499 was mainly located in the basement section of seminiferous tubules of prepubertal porcine testicular tissue. Overexpression of miR-499 promoted cell proliferation and inhibited apoptosis, whereas miR-499 inhibition resulted in the opposite effect. The PTEN gene was directly targeted by miR-499, and the expression of mRNA and protein was also negatively regulated by miR-499 in immature porcine Sertoli cells. siRNA-induced PTEN knockdown resulted in a similar effect as an overexpression of miR-499 and abolished the effects of miR-499 inhibition on immature porcine Sertoli cells. Moreover, both miR-499 overexpression and the PTEN knockdown activated the PI3K/AKT signaling pathway, whereas inhibition of the PI3K/AKT signaling pathway caused immature porcine Sertoli cell apoptosis and inhibited cell proliferation. Overall, miR-499 promotes proliferation and inhibits apoptosis in immature porcine Sertoli cells through the PI3K/AKT pathway by targeting the PTEN gene. This study provides novel insights into the effects of miR-499 in spermatogenesis through the regulation of immature Sertoli cell proliferation and apoptosis.

Mutational Loss of PTEN Induces Resistance to NOTCH1 Inhibition in T-ALL.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5-5
Author(s):  
Adolfo Ferrando ◽  
Teresa Palomero ◽  
Maria Luisa Sulis ◽  
Maria Cortina ◽  
Pedro J. Real ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Growth ◽  
Tumor Suppressor ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Pathway ◽  
Akt Signaling Pathway ◽  
Notch1 Signaling ◽  
Shrna Knockdown

Abstract Activating mutations in NOTCH1 are common in T-cell lymphoblastic leukemias (T-ALL), making this receptor a promising target for drugs such as gamma-secretase inhibitors (GSIs), which block NOTCH1 activation. However, enthusiasm for these therapies has been tempered by tumor resistance and the paucity of information on the oncogenic programs regulated by NOTCH1. Here, we identify the loss of the PTEN tumor suppressor gene and activation of the PI3K-AKT signaling pathway as critical factors that determine the resistance of T-ALL cells to inhibition of NOTCH1 signaling with GSIs. Mutational loss of PTEN is found in 17% of T-ALL cases and in the majority of T-ALL cell lines. Importantly, 8/8 T-ALL lines sensitive to NOTCH inhibition with GSIs retain wild type PTEN, while this tumor suppressor is lost in 8/8 GSI-resistant T-ALLs analyzed (P<0.001). Furthermore, both the expression of a constitutively active form of AKT (Myr AKT) and PTEN shRNA knockdown induced resistance to GSIs in T-ALLs and promoted cell growth, proliferation and glucose metabolism. The close association between GSI resistance and PTEN loss prompted us to analyze the interaction between NOTCH1 signaling and the PI3K-AKT pathway. Analysis of normal and leukemic T-cells demonstrated that NOTCH1 signaling regulates PTEN expression and AKT signaling. Thus, inhibition of NOTCH1 with GSIs results in transcriptional upregulation of PTEN and concomitant downregulation of PI3K/AKT signaling in T-ALL. A similar effect -transcriptional upregulation of Pten upon loss of Notch signaling- was observed in primary mouse thymocytes, which are highly dependent on Notch1 to sustain the activity of the Akt signaling pathway. ChIP-on-chip and reporter assays demonstrate that regulation of PTEN is mediated by HES1, a transcriptional repressor directly controlled by NOTCH1. In agreement with these observations, HES1 shRNA knockdown induced transcriptional upregulation of PTEN in T-ALL cells. These results were perfectly recapitulated in a Drosophila model of Notch-induced tumorigenesis. Thus, activation of Notch signaling via expression of Delta and activation of the PI3K-AKT pathway by Akt showed marked synergism in tumor formation in the fly eye. Importantly, also in Drosophila, activation of Akt reverses the growth defect phenotype induced by the loss of Notch signaling, highlighting the importance of the interaction between these two pathways for the control of cell growth. Finally, we proposed that mutational loss of PTEN could induce an oncogene addition switch that makes T-ALL cells resistant to NOTCH inhibitors but enhanced their sensitivity to AKT inhibitors. Treatment with SH-6, a phosphatidylinositol analog inhibitor of AKT, showed a strong antileukemic effect against GSI-resistant/PTEN-null T-ALLs but not against GSI-sensitive/PTEN-positive cells, confirming this hypothesis. These results demonstrate the importance of the interaction of NOTCH1 with the PI3K-AKT pathway in T-cell homeostasis and response to therapy and provide the basis for the design of new therapeutic strategies for T-ALL.

scholarly journals Overexpression of sperm associated antigen 5 promotes cell growth, metastasis, and adriamycin resistance in esophageal squamous cell carcinoma via activating PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Yan Yan ◽  
Fang bin Zhang ◽  
Qiao li Yi ◽  
Kun Zhou
Keyword(s):  
Cell Growth ◽  
Prognostic Factor ◽  
Signaling Pathway ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Pathway Enrichment Analysis ◽  
Akt Signaling Pathway ◽  
Ppi Network ◽  
Cox Regression Analysis ◽  
Antigen 5

Abstract Background: Esophageal cancer (ESCC) is one of the most common malignant tumors in the digestive system. This study aims to explore the effects of sperm associated antigen 5 (SPAG5) on cell growth, metastasis, and azithromycin resistance in esophagus cancer and its molecular mechanism.Methods: The DEGs were obtained from GSE92396, GSE17351, and GSE9982 datasets about ESCC. The PPI network was constructed using the STRING database and was visualized using Cytoscape software. The cytohubba plug-in of Cytoscape software was used to identify the hub genes of the PPI network. The DEGs were used to perform GO and KEGG pathway enrichment analysis using the DAVID database. Statistical analysis was performed to test the clinical and prognostic significance of SPAG5. Cell viability, proliferation, apoptosis, migration, and invasion were detected using CCK-8, colony formation, flow cytometry, transwell and scratch-wound assays. The expression of related genes was detected by qRT-PCR, western blot and IHC assays. The oncogenicity of SPAG5 in ESCC cells was determined using the nude mouse transplantation tumor experiment.Results: Ninety-three overlapping genes from the DEGs were used to construct the PPI network, and mainly enriched in BP, CC, and MF terms. COX regression analysis of OS showed that SPAG5 expression and pN category were correlated with OS. Univariate and multivariate analyses showed that SPAG5 was an independent prognostic factor for OS in ESCC. The ROC curve analysis showed the AUC of SPAG5 was 0.74. Multiple logistic regression showed that SPAG5 were subsequently identified as an independent risk factor associated with OS. SPAG5 overexpression was detected in ESCC tissues and cell lines, and improved cell proliferation. SPAG5 knockdown reduced cell growth and metastasis and promoted its apoptosis. The functions of SPAG5 overexpression promoting ESCC cell growth and affecting cleaved caspase-3, Ki67, VEGF, and MMP-2/-9 expression were reversed by PI3K/AKT inhibitor. SPAG5 overexpression enhanced resistance to ADM in EC9706 and Eca109 cells and it was closely related to the activation of PI3K/AKT signaling pathway.Conclusion: The overexpression of SPAG5 was an independent good prognostic factor and promoted the proliferation, invasion, migration, and ADM resistance, and inhibited the apoptosis via activating PI3K/AKT signaling pathway in ESCC.

scholarly journals Retraction: Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signaling pathway in IL-1β-induced osteoarthritis chondrocytes

RSC Advances ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 4441-4441
Author(s):  
Laura Fisher
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Cell Apoptosis ◽  
Akt Signaling ◽  
Salvianolic Acid B ◽  
Signalling Pathway ◽  
Akt Signaling Pathway ◽  
Salvianolic Acid ◽  
Osteoarthritis Chondrocytes

Retraction of ‘Salvianolic acid B inhibits inflammatory response and cell apoptosis via the PI3K/Akt signalling pathway in IL-1β-induced osteoarthritis chondrocytes’ by Bin Zhu et al., RSC Adv., 2018, 8, 36422–36429, DOI: 10.1039/C8RA02418A.

scholarly journals Girdin regulates the migration and invasion of glioma cells via the PI3K-Akt signaling pathway

2015 ◽  
Vol 12 (4) ◽  
pp. 5086-5092 ◽  
Author(s):  
WEIMIN NI ◽  
YAN FANG ◽  
LEI TONG ◽  
ZHAOXUE TONG ◽  
FUXIN YI ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Glioma Cells ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway

scholarly journals PI3K/AKT Signaling Pathway Mediates the Proliferation, Migration and Invasion of Papillary Craniopharyngioma Cells

2020 ◽  
Author(s):  
Lin Zhou ◽  
Cheng Xing Yang ◽  
Lin Chun Fang ◽  
You Yuan Bao ◽  
Zhi Gang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Cell Counting ◽  
Migration And Invasion ◽  
Specific Cell ◽  
Primary Cells ◽  
Akt Signaling Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Growth And Survival ◽  
Pi3k Signaling Pathway

Abstract Objective:Craniopharyngiomas are rare, histologically benign but clinically challenging neoplasms. Here, we aimed to interrogate the effect and significance of Phosphatidylinositol-3-kinase (PI3K) signaling pathway on papillary craniopharyngioma (PCP) cell growth and survival.Methods: We used Western blotting (WB) experiments to evaluate the expression of the PI3K/protein kinase B (AKT) in Craniopharyngiomas tissues, relative to health tissues. Primary tumor cells were obtained from fresh PCP samples by cell culture and then determined by cell morphology, immunofluorescence staining and expression of specific cell markers. In this study, PCP cell lines, isolated from fresh PCP samples, were treated with different concentrations of LY294002, a PI3K/AKT signaling inhibitor, to evaluate their proliferation, migration and invasion. We determined the cell proliferation using Cell Counting Kit-8 and colony formation. We then used flow cytometry to evaluate cell apoptosis and cell cycle. In addition, cell migration and invasion levels were determined by wound healing and Transwell assays, respectively.Results: Our data demonstrated that the expression of phosphorylated-PI3K/AKT was upregulated in human craniopharyngioma tissues compared to the normal control tissues. Immunofluorescence assays showed the presence of cytokeratin (pan CK) and vimentin protein (VIM) in the PCP primary cells. Furthermore, inhibition of PI3K/AKT signaling blocks the proliferation, migration and invasion of the PCP primary cells.Conclusions:Taken together, our data robustly demonstrates that the PI3K/AKT signaling pathway mediates the proliferation, migration and invasion of the PCP cells.

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