circPUM1 Activates the PI3K/AKT Signaling Pathway by Sponging to Promote to Promote the Proliferation, Invasion and Glycolysis of Pancreatic Cancer

Background: Our study seeks to obtain data to assess the impacts of circPUM1 on pancreatic cancer (PC) and its mechanism. Methods: The expression of circPUM1 and miR-200c-3p in PC and normal tissues and PC cell lines was collected and detected. Subsequently, dual-luciferase assay-based verification of the binding site of the two was carried out. After interfering with circPUM1 expression in MIAPaCa-2 and PANC-1 cells, cell proliferation, viability, apoptosis rate, invasion ability, glucose consumption, and lactate production were measured by MTT, colony formation, flow cytometry, Transwell assays, and glucose and lactate assay kits. Additionally, western blot was utilized for assessing PI3K/AKT signaling pathway-related proteins. From the results, highly expressed circPUM1 and miR-200c-3p in PC tissues and cells were proved. Results: Down-regulation of circPUM1 expression significantly inhibited cell proliferation, cell viability, invasion, and glycolysis, while increasing the apoptosis rate. Down-regulated circPUM1 led to the inhibition of the PI3K/AKT signaling pathway activity in PC cells, while up-regulated circPUM1 increased its activity. Further experiments revealed that down-regulation of miR-200c-3p expression reversed the inhibitory effect of lowly expressed circPUM1 on PC cells. Conclusion: In summary, circPUM1 activates PI3K/AKT signaling pathway by sponging miR-200c-3p and promotes PC progression.

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S100A11 promotes human pancreatic cancer PANC‑1 cell proliferation and is involved in the PI3K/AKT signaling pathway

Oncology Letters ◽

10.3892/ol.2017.7295 ◽

2017 ◽

Cited By ~ 4

Author(s):

Mingbing Xiao ◽

Tao Li ◽

Yifei Ji ◽

Feng Jiang ◽

Wenkai Ni ◽

...

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Akt Signaling ◽

Human Pancreatic Cancer ◽

Akt Signaling Pathway

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Knockdown of Annexin-A1 Inhibits Growth, Migration and Invasion of Glioma Cells by Suppressing the PI3K/Akt Signaling Pathway

ASN NEURO ◽

10.1177/17590914211001218 ◽

2021 ◽

Vol 13 ◽

pp. 175909142110012

Author(s):

Liqing Wei ◽

Li Li ◽

Li Liu ◽

Ru Yu ◽

Xing Li ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Glioma Cell ◽

Combined Treatment ◽

Glioma Cells ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway ◽

Down Regulation ◽

Glioma Cell Proliferation

ANXA1, which can bind phospholipid in a calcium dependent manner, is reported to play a pivotal role in tumor progression. However, the role and mechanism of ANXA1 involved in the occurrence and development of malignant glioma are still not well studied. Therefore, we explored the effects of ANXA1 on normal astrocytes and glioma cell proliferation, apoptosis, migration and invasion and the underlying mechanisms. We found that ANXA1 was markedly up-regulated in glioma cell lines and glioma tissues. Down-regulation of ANXA1 inhibited normal astrocytes and glioma cell proliferation and induced the cell apoptosis, which suggested that the consequences of loss of Annexin 1 are not specific to the tumor cells. Furthermore, the siRNA-ANXA1 treatment significantly reduced tumor growth rate and tumor weight. Moreover, decreasing ANXA1 expression caused G2/M phase arrest by repressing expression levels of cdc25C, cdc2 and cyclin B1. Interestingly, ANXA1 did not affect the expressions of β-catenin, GSK-3β and NF-κB, the key signaling molecules associated with cancer progression. However, siRNA-ANXA1 was found to negatively regulate phosphorylation of AKT and the expression and activity of MMP2/-9. Finally, the decrease of cell proliferation and invasiveness induced by ANXA1 down-regulation was partially reversed by combined treatment with AKT agonist insulin-like growth factor-1 (IGF-1). Meanwhile, the inhibition of glioma cell proliferation and invasiveness induced by ANXA1 down-regulation was further enhanced by combined treatment with AKT inhibitor LY294002. In summary, these findings demonstrate that ANXA1 regulates proliferation, migration and invasion of glioma cells via PI3K/AKT signaling pathway.

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Mir10a aggravates the ischemia-reperfusion kidney injury by inhibiting the PI3K/AKT signaling pathway

10.21203/rs.2.23453/v1 ◽

2020 ◽

Author(s):

Dongsheng Xu ◽

Wenjun Li ◽

Tao Zhang ◽

Gang Wang

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Renal Injury ◽

Ischemia Reperfusion ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Rt Pcr ◽

Apoptosis Rate ◽

Related Proteins

Abstract Background To investigate the effect of miR-10a on PI3K/AKT signaling pathway. The ischemia-reperfusion injury models of rats were simulated in vivo . Methods RT-PCR was used to test the expression of miR-10a. The serum creatinine and urea nitrogen levels were determined. The pathological changes and the apoptosis of renal cells were observed. The model of HK-2 cells with hypoxia-reoxygenation was established in vitro. The cell proliferation and apoptosis rate were tested by CCK8, clone formation and flow cytometry, respectively. The apoptosis-related proteins and PIK3CA and PI3K/AKT signaling pathway-related proteins were detected by Western blot both in vivo and intro . The dual luciferase assay was used to verify whether PIK3CA is a target gene of miR-10a. PIK3CA gene was over-expression or silenced. The transfection efficiency was verified by RT-PCR and the above experiments were repeated. Results Compared with I/R group, miR-10a RNA was significantly increased in renal tissue of miR-10a group, serum Cr and BUN levels, and renal injury score and apoptosis index were significantly increased, while the expression of PI3K/AKT signaling pathway-related proteins were significantly inhibited. However, the indicators above were contrary in anti-miR group. In comparison with H/R group, miR-10a RNA expression was remarkably increased in miR-10a cells and the cell proliferation was inhibited. The apoptosis rate was increased and the expression of PI3K/AKT signaling pathway-related proteins were down-regulated. However, the indicators above were contrary in anti-miR group. Conclusion miR-10a can aggravate the ischemia-reperfusion-induced renal injury in rats by targeting PIK3CA and inhibitingPI3K/AKT signaling pathway.

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GSK2126458 has the potential to inhibit the proliferation of pancreatic cancer uncovered by bioinformatics analysis and pharmacological experiments

Journal of Translational Medicine ◽

10.1186/s12967-021-03050-7 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yueqin Feng ◽

Yuguan Jiang ◽

Fengjin Hao

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Mtor Inhibitors ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Hub Genes ◽

Pancreatic Cancer Cells ◽

Proliferation And Invasion

Abstract Background Pancreatic cancer is one of the most serious digestive malignancies. At present, there is an extreme lack of effective strategies in clinical treatment. The purpose of this study is to identify key genes and pathways in the development of pancreatic cancer and provide targets for the treatment of pancreatic cancer. Methods GSE15471 and GSE62165 were used to screen differentially expressed genes by GEO2R tool. Hub genes prognostic potential assessed using the GEPIA and Kaplan–Meier plotter databases. The drug susceptibility data of pan-cancer cell lines is provided by The Genomics of Drug Sensitivity in Cancer Project (GDSC). Finally, the effects of PI3K–Akt signaling pathway inhibitors on cell viability of pancreatic cancer cells were detected by cell proliferation and invasion assays. Results A total of 609 differentially expressed genes were screened and enriched in the focal adhesion, phagosome and PI3K–Akt signaling pathway. Of the 15 hub genes we found, four were primarily associated with the PI3K–Akt signaling pathway, including COL3A1, EGF, FN1 and ITGA2. GDSC analysis showed that mTOR inhibitors are very sensitive to pancreatic cancer cells with mutations in EWSR1.FLI1 and RNF43. Cell proliferation and invasion results showed that mTOR inhibitors (GSK2126458) can inhibit the proliferation of pancreatic cancer cells. Conclusions This study suggested that the PI3K–Akt signaling pathway may be a key pathway for pancreatic cancer, our study uncovered the potential therapeutic potential of GSK2126458, a specific mTOR inhibitor, for pancreatic cancer.

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CBX7 suppresses cell proliferation, migration and invasion by inhibiting PI3K/Akt signaling pathway in pancreatic cancer

Pancreatology ◽

10.1016/j.pan.2015.12.175 ◽

2016 ◽

Vol 16 (1) ◽

pp. S60

Author(s):

S.J. Ni ◽

H.W. Wang ◽

Z.X. He ◽

W. Wang

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Signaling Pathway ◽

Akt Signaling ◽

Migration And Invasion ◽

Akt Signaling Pathway

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MiRNA-132 regulates the development of osteoarthritis in correlation with the modulation of PTEN/PI3K/AKT signaling

BMC Geriatrics ◽

10.1186/s12877-021-02046-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Wei Zhang ◽

Chengfang Hu ◽

Chi Zhang ◽

Congfeng Luo ◽

Biao Zhong ◽

...

Keyword(s):

Cell Proliferation ◽

Signaling Pathway ◽

Akt Signaling ◽

Joint Disease ◽

Inflammatory Factors ◽

Akt Signaling Pathway ◽

Sprague Dawley ◽

Down Regulation ◽

Destructive Effect ◽

Bax Protein

Abstract Background Osteoarthritis (OA) is a commonly known prevalent joint disease, with limited therapeutic methods. This study aimed to investigate the functions of miRNA-132 (miR-132) in the modulation of PTEN/PI3K/AKT signaling pathway in the development and progression of osteoarthritis. Methods Eight male osteoarthritic patients and eight healthy males were recruited. Male Sprague Dawley (SD) rats were used for cellular experiments. QRT-PCR was performed to detect the expression levels of miR-132, PTEN, PI3K and AKT. MTT assay and apoptosis assay were carried out to measure the cell proliferation rate and cell apoptosis rate, respectively. Western blotting was employed to detect the protein expression of related RNAs and inflammatory factors. Results In osteoarthritic patients, the expression level of miR-132 was decreased, compared with that in the normal group. Over-expression of miR-132 elevated cell proliferation and decreased apoptosis of chondrocytes. Down-regulation of miR-132 decreased cell proliferation and induced apoptosis in chondrocytes. In addition, down-regulation of miR-132 promoted the expression of Bax protein and activated caspase-3/9, increased inflammation divisors. PTEN inhibitor antagonized the destructive effect of the miR-132 inhibitor on cell proliferation of chondrocytes. PI3K inhibitor increased the destructive effect of the miR-132 inhibitor on osteoarthritis. Conclusion In conclusion, miR-132 is an important regulator of osteoarthritis in chondrocytes through the PTEN/PI3K/AKT signaling pathway.

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ERas regulates cell proliferation and epithelial–mesenchymal transition by affecting Erk/Akt signaling pathway in pancreatic cancer

Human Cell ◽

10.1007/s13577-020-00401-2 ◽

2020 ◽

Vol 33 (4) ◽

pp. 1186-1196

Author(s):

Yang Liu ◽

Peng Qin ◽

Rong Wu ◽

Lianfang Du ◽

Fan Li

Keyword(s):

Pancreatic Cancer ◽

Cell Proliferation ◽

Cancer Cells ◽

Signaling Pathway ◽

Colony Formation ◽

Epithelial Mesenchymal Transition ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Mesenchymal Transition ◽

Pancreatic Cancer Cells

Abstract Pancreatic cancer is the fourth most common lethal malignancy with an overall 5-year survival rate of less than 5%. ERas, a novel Ras family member, was first identified in murine embryonic stem cells and is upregulated in various cancers. However, the expression and potential role of ERas in pancreatic cancer have not been investigated. In this study, we found that ERas mRNA and protein were upregulated in pancreatic cancer tissues and cells compared with controls. Knockdown of ERas in pancreatic cancer cells by siRNA significantly decreased cell proliferation, colony formation, migration, and invasion and promoted cell apoptosis in vitro. Epithelial–mesenchymal transition (EMT) is closely related to tumor progression. We observed a significant decrease in N-cadherin expression in pancreatic cancer cells in response to ERas gene silencing by immunofluorescence assay and western blot. Furthermore, tumor growth and EMT were inhibited in xenografts derived from pancreatic cancer cells with ERas downregulation. We further investigated the regulatory mechanisms of ERas in pancreatic cancer and found that ERas may activate the Erk/Akt signaling pathway. Moreover, Erk inhibitor decreased pancreatic cancer cells proliferation and colony formation activities. Our data suggest that targeting ERas and its relevant signaling pathways might represent a novel therapeutic approach for the treatment of pancreatic cancer.

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CircRILPL1 promotes muscle proliferation and differentiation via binding miR-145 to activate IGF1R/PI3K/AKT pathway

Cell Death and Disease ◽

10.1038/s41419-021-03419-y ◽

2021 ◽

Vol 12 (2) ◽

Author(s):

Xuemei Shen ◽

Jia Tang ◽

Rui Jiang ◽

Xiaogang Wang ◽

Zhaoxin Yang ◽

...

Keyword(s):

Signaling Pathway ◽

Muscle Development ◽

Inhibitory Effect ◽

Akt Signaling ◽

Luciferase Assay ◽

Circular Rnas ◽

Akt Signaling Pathway ◽

Sequencing Data ◽

Proliferation And Differentiation ◽

Myoblast Proliferation

AbstractMany novel non-coding RNAs, such as microRNAs (miRNAs) and circular RNAs (circRNAs), are involved in various physiological and pathological processes. The PI3K/AKT signaling pathway is important for its role in regulating skeletal muscle development. In this study, molecular and biochemical assays were used to confirm the role of miRNA-145 (miR-145) in myoblast proliferation and apoptosis. Based on sequencing data and bioinformatics analysis, we identified a new circRILPL1, which acts as a sponge for miR-145. The interactions between circRILPL1 and miR-145 were examined by bioinformatics, a luciferase assay, and RNA immunoprecipitation. Mechanistically, knockdown or exogenous expression of circRILPL1 in the primary myoblasts was performed to prove the functional significance of circRILPL1. We investigated the inhibitory effect of miR-145 on myoblast proliferation by targeting IGF1R to regulate the PI3K/AKT signaling pathway. A novel circRILPL1 was identified that could sponge miR-145 and is related to AKT activation. In addition, circRILPL1 was positively correlated with muscle proliferation and differentiation in vitro and could inhibit cell apoptosis. The newly identified circRILPL1 functions as a miR-145 sponge to regulate the IGF1R gene and rescue the inhibitory effect of miR-145 on the PI3K/AKT signaling pathway, thereby promoting myoblast growth.

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