Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

MiR-3188 Inhibits Non-small Cell Lung Cancer Cell Proliferation Through FOXO1-Mediated mTOR-p-PI3K/AKT-c-JUN Signaling Pathway.

ABSTRACT: This study investigated the role of miR-3188 on the proliferation of non-small cell lung cancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small cell lung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achieved by lentiviral transfection. Cell proliferation was assessed by immunohistochemical staining of Ki67 and PCNA, Edu incorporation, and colony formation assay. Western blotting was used to examine expression of FOXO1, mTOR, p-mTOR, CCND1, p21, c-JUN, AKT, pAKT, PI3K, p-PI3K, and p27 proteins. It was found that miR-3188 reduced cell proliferation in NSCLC cells. Molecular analyses indicated that the effect of mammalian target of rapamycin (mTOR) was directly mediated by miR-3188, leading to p-PI3K/p-AKT/c-JUN inactivation. The inhibition of this signaling pathway further caused cell-cycle suppression. Moreover, FOXO1 was found to be involved in regulating the interaction of miR-3188 and mTOR through p-PI3K/p-AKT/c-JUN signaling pathway. Taken together, our study demonstrated that miR-3188 interacts with mTOR and FOXO1 to inhibit NSCLC cell proliferation through a mTOR-p-PI3K/AKT-c-JUN signaling pathway. Therefore, miR-3188 might be a potential target for the treatment of NSCLC.

SUBMITTER: Wang C

PROVIDER: S-EPMC6297856 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

miR-3188 regulates nasopharyngeal carcinoma proliferation and chemosensitivity through a FOXO1-modulated positive feedback loop with mTOR-p-PI3K/AKT-c-JUN.

Project description:The biological role of miR-3188 has not yet been reported in the context of cancer. In this study, we observe that miR-3188 not only reduces cell-cycle transition and proliferation, but also significantly prolongs the survival time of tumour-bearing mice as well as sensitizes cells to 5-FU. Mechanistic analyses indicate that miR-3188 directly targets mTOR to inactivate p-PI3K/p-AKT/c-JUN and induces its own expression. This feedback loop further suppresses cell-cycle signalling through the p-PI3K/p-AKT/p-mTOR pathway. Interestingly, we also observe that miR-3188 direct targeting of mTOR is mediated by FOXO1 suppression of p-PI3K/p-AKT/c-JUN signalling. In clinical samples, reduced miR-3188 is an unfavourable factor and negatively correlates with mTOR and c-JUN levels but positively correlates with FOXO1 expression. Our studies demonstrate that as a tumour suppressor, miR-3188 directly targets mTOR to stimulate its own expression and participates in FOXO1-mediated repression of cell growth, tumorigenesis and NPC chemotherapy resistance.

| S-EPMC4842991 | biostudies-literature

Down-Regulation of SREBP via PI3K/AKT/mTOR Pathway Inhibits the Proliferation and Invasion of Non-Small-Cell Lung Cancer Cells.

Project description:Background:Lung cancer is one of the most common causes of cancer-related deaths worldwide, metabolic disorders are also a problem that puzzles mankind. SREBP is overexpressed in non-small-cell lung cancer (NSCLC) and is also a key regulator of lipid synthesis. However, the mechanisms by which SREBP regulates the proliferation, migration and invasion in NSCLC remain unclear. Materials and Methods:CCK-8, colony formation assay, soft agar assay, scratch wound healing assay and transwell assays were performed to detect proliferation, and invasion in NSCLC cells, respectively. In addition, Western blotting assay, qPCR and immunofluorescence were applied to detect the expressions of SREBP1, SREBP2, ki-67, PCNA, Bax, bcl-2, E-cadherin, N-cadherin, Vimentin, PI3K, p-PI3k, AKT, p-AKT, mTOR, p-mTOR in NSCLC cells. Results:In this study, downregulation of SREBP significantly inhibited the proliferation, migration and invasion of A549 and H1299 cells. Moreover, the method of piecewise inhibition was adopted to prove that SREBP is a downstream molecule of the PI3K/Akt/mTOR signaling pathway. Conclusion:Our study indicated that downregulation of SREBP inhibited the growth in NSCLC cells via PI3K/AKT/mTOR signaling pathway. Thus, we suggested SREBP may serve as a potential target for the treatment of patients with NSCLC.

| S-EPMC7490059 | biostudies-literature

HRK inhibits colorectal cancer cells proliferation by suppressing the PI3K/AKT/mTOR pathway.

Project description:BackgroundAs one of the most common malignant tumor, colorectal cancer (CRC) continues to have a high incidence and mortality rate. HRK belongs to the BCL-2 protein family, which has been shown to have antitumor effects in prostate cancer. However, its role in colorectal cancer is not yet known.MethodsIn this study, we verified the expression levels of HRK in colorectal cancer tissues by public database search as well as immunohistochemistry. Next, we analyzed HRK expression levels in CRC tissues,adjacent non-cancerous tissues, cell lines and normal intestinal epithelial cells by qPCR and Western blotting. CCK-8 proliferation assays, transwell assays, wound healing assays, colony assays and flow cytometry were performed to clarified the effect of HRK on CRC cells. Western blotting and rescue experiments were used to determine the role of HRK in regulating PI3K/AKT/mTOR signaling pathway.ResultsHRK expression was lower in CRC tissues and cell lines. Gain and loss of function experiments showed that HRK decreased proliferation, invasion and migration of CRC cells. Low expression of HRK inhibited CRC cell apoptosis as well as activated the PI3K/AKT/mTOR signaling pathway. In addition, rapamycin inhibits the activation of PI3K/AKT/mTOR signaling pathway and reverses HRK-induced alterations in cell biological functions.ConclusionOur study demonstrates that HRK is lowly expressed in colorectal cancer tissues. And for the first time, HRK was shown to promote apoptosis and inhibit proliferation of colorectal cancer cells by inhibiting PI3K/AKT/mTOR signaling pathway. HRK represents a potential target for the treatment of CRC.

| S-EPMC9769574 | biostudies-literature

Serine Protease from Nereis virens Inhibits H1299 Lung Cancer Cell Proliferation via the PI3K/AKT/mTOR Pathway.

Project description:This study explores the in vitro anti-proliferative mechanism between Nereis Active Protease (NAP) and human lung cancer H1299 cells. Colony formation and migration of cells were significantly lowered, following NAP treatment. Flow cytometry results suggested that NAP-induced growth inhibition of H1299 cells is linked to apoptosis, and that NAP can arrest the cells at the G0/G1 phase. The ERK/MAPK and PI3K/AKT/mTOR pathways were selected for their RNA transcripts, and their roles in the anti-proliferative mechanism of NAP were studied using Western blots. Our results suggested that NAP led to the downregulation of p-ERK (Thr 202/Tyr 204), p-AKT (Ser 473), p-PI3K (p85), and p-mTOR (Ser 2448), suggesting that NAP-induced H1299 cell apoptosis occurs via the PI3K/AKT/mTOR pathway. Furthermore, specific inhibitors LY294002 and PD98059 were used to inhibit these two pathways. The effect of NAP on the downregulation of p-ERK and p-AKT was enhanced by the LY294002 (a PI3K inhibitor), while the inhibitor PD98059 had no obvious effect. Overall, the results suggested that NAP exhibits antiproliferative activity by inducing apoptosis, through the inhibition of the PI3K/AKT/mTOR pathway.

| S-EPMC6627947 | biostudies-literature

SH2B1 promotes NSCLC cell proliferation through PI3K/Akt/mTOR signaling cascade.

Project description:BackgroundNon-small cell lung cancer (NSCLC), the most prevalent type of human lung cancer, is characterized by many molecular abnormalities. SH2B1, a member of the SH2-domain containing family, have recently been shown to act as tumor activators in multiple cancers. The objective of this study was to investigate the role SH2B1 and the underlying molecular mechanism in NSCLC.MethodsCell functional analysis and cell line-derived xenograft model were performed to determine SH2B1 potential roles on NSCLC cell proliferation in vitro and in vivo. In vitro assays were performed to identify signal molecular mechanisms. Subsequently, 104 patients with NSCLC undergoing primary surgical resection were recruited to evaluated expression of SH2B1 and Akt/mTOR signaling markers by immunohistochemical staining to determine their clinicopathologic significance.ResultsModulation of SH2B1 expression levels had distinct effects on cell proliferation, cell cycle and apoptosis in the NSCLC cell lines A549 and H1299. At the molecular level, overexpression of SH2B1 resulted in the upregulation of the Akt/mTOR markers, p-Akt and p-mTOR, and downregulation of PTEN to promote NSCLC cell proliferation, while silencing SH2B1 had the opposite effect. In human NSCLC specimens, SH2B1 expression levels were positively associated with Akt/mTOR signaling pathway markers.ConclusionsThe SH2B1/Akt/mTOR/PTEN axis is required for regulating NSCLC cell proliferation and might prove to be a promising strategy for restraining tumor progression in NSCLC patients.

| S-EPMC6127928 | biostudies-literature

MiR-206 inhibits HGF-induced epithelial-mesenchymal transition and angiogenesis in non-small cell lung cancer via c-Met /PI3k/Akt/mTOR pathway.

Project description:MiR-206 is low expression in lung cancers and associated with cancer metastasis. However, the roles of miR-206 in epithelial-mesenchymal transition (EMT) and angiogenesis in lung cancer remain unknown. In this study, we find that hepatocyte growth factor (HGF) induces EMT, invasion and migration in A549 and 95D lung cancer cells, and these processes could be markedly inhibited by miR-206 overexpression. Moreover, we demonstrate that miR-206 directly targets c-Met and inhibits its downstream PI3k/Akt/mTOR signaling pathway. In contrast, miR-206 inhibitors promote the expression of c-Met and activate the PI3k/Akt/mTOR signaling, and this effect could be attenuated by the PI3K inhibitor. Moreover, c-Met overexpression assay further confirms the significant inhibitory effect of miR-206 on HGF-induced EMT, cell migration and invasion. Notably, we also find that miR-206 effectively inhibits HGF-induced tube formation and migration of human umbilical vein endothelial cells (HUVECs), and the mechanism is also related to inhibition of PI3k/Akt/mTOR signaling. Finally, we reveal the inhibitory effect of miR-206 on EMT and angiogenesis in xenograft tumor mice model. Taken together, miR-206 inhibits HGF-induced EMT and angiogenesis in lung cancer by suppressing c-Met/PI3k/Akt/mTOR signaling. Therefore, miR-206 might be a potential target for the therapeutic strategy against EMT and angiogenesis of lung cancer.

| S-EPMC4951285 | biostudies-literature

miR-5188 augments glioma growth, migration and invasion through an SP1-modulated FOXO1-PI3K/AKT-c-JUN-positive feedback circuit.

Project description:The biological effect and molecular mechanism of miR-5188 have not been thoroughly investigated. The study aims at elucidating the role of miR-5188 in glioma progression. Human glioma cell lines and tissues were used for functional and expression analysis. Cellular and molecular techniques were performed to explore the functions and mechanisms of miR-5188 in glioma. In our investigation, we demonstrated that miR-5188 promoted cell proliferation, the G1/S transition of the cell cycle, migration and invasion in glioma and reduced the lifespan of glioma-bearing mice. miR-5188 directly targeted FOXO1 and activated PI3K/AKT-c-JUN signalling, which enhanced miR-5188 expression. Moreover, the c-JUN transcription factor functionally bound to the miR-5188 promoter region, forming the positive feedback loop. The feedback loop promoted glioma progression through activating the PI3K/AKT signalling, and this loop is augmented by the interaction between SP1 and c-JUN. Moreover, it was also found that the miR-5188/FOXO1 axis is facilitated by SP1-activated PI3K/AKT/c-JUN signalling. In glioma samples, miR-5188 expression was found to be an unfavourable factor and was positively associated with the mRNA levels of SP1 and c-JUN, whereas negatively associated with the mRNA levels of FOXO1. Our investigation demonstrates that miR-5188 could function as a tumour promoter by directly targeting FOXO1 and participating in SP1-mediated promotion of cell growth and tumorigenesis in glioma.

| S-EPMC7579714 | biostudies-literature

WT1-interacting protein inhibits cell proliferation and tumorigenicity in non-small-cell lung cancer via the AKT/FOXO1 axis.

Project description:Lung cancer is the most common cancer and the leading cause of cancer-related death worldwide; hence, it is imperative that the mechanisms underlying the malignant properties of lung cancer be uncovered in order to efficiently treat this disease. Increasing evidence has shown that WT1-interacting protein (WTIP) plays important roles both physiologically and pathologically in humans; however, the role of WTIP in cancer is unknown. Here, we investigated the role and mechanism of WTIP in cell proliferation and tumorigenesis of non-small-cell lung cancer (NSCLC). We report that WTIP is a tumor suppressor in human NSCLC. We found that WTIP expression was significantly reduced in both NSCLC cell lines and clinical specimens compared to that in normal controls; this reduction was largely attributed to promoter hypermethylation. Downregulation of WTIP significantly correlates with poor prognosis and predicts a shorter overall survival and progression-free survival among NSCLC patients. Moreover, ectopic overexpression of WTIP dramatically inhibits cell proliferation and tumorigenesis in vitro and in vivo; conversely, depletion of WTIP expression shows the opposite effects. Mechanistically, WTIP impairs AKT phosphorylation and activation, leading to enhanced expression and transcriptional activity of FOXO1, which further increases p21Cip1 and p27Kip1, and decreases cyclin D1, which consequently results in cell cycle arrest. Collectively, the results of the current study indicate that WTIP is an important proliferation-related gene and that WTIP expression may represent a novel prognostic biomarker for NSCLC.

| S-EPMC6487700 | biostudies-literature

Silencing c-Jun inhibits autophagy and abrogates radioresistance in nasopharyngeal carcinoma by activating the PI3K/AKT/mTOR pathway.

Project description:BackgroundRadioresistance plays an important role in the failure of radiotherapy (RT) for nasopharyngeal carcinoma (NPC), leading to poor prognosis. The purpose of this study was to explore the relationship between the expression of the c-Jun oncogene and the prognosis of NPC. In addition, we investigated the potential mechanisms of c-Jun in the regulation of tumor growth and radioresistance in NPC.Methodsc-Jun expression in NPC tissues and nasopharyngeal mucosa tissues was evaluated using immunochemistry. c-Jun and its downstream targets were verified by dual-luciferase reporter assays. Inhibitors or activators were used to interfere with the PI3K/AKT/mTOR pathway. Protein expression was analyzed by western blotting. NPC nude mouse xenograft models were used to investigate the potential effects of c-Jun and ionizing radiation in vivo.ResultsThe expression of c-Jun in NPC tissues was significantly higher than that in normal nasopharyngeal mucosa (NNM) tissues, and Cox regression analysis revealed that c-Jun overexpression was an independent risk factor for poor prognosis in NPC patients. Both in vitro and in vivo experiments verified that c-Jun targeted PI3K/AKT signaling. We also performed an in vivo study showing that c-Jun knockdown effectively suppressed NPC growth in a xenograft tumor model by autophagy inhibition, and these effects were accompanied by the upregulation of p-PI3K p-AKT, p-mTOR, and P62 and downregulation of LC3-II expression.ConclusionsHigh expression of c-Jun was correlated with poor prognosis in NPC patients. c-Jun knockdown increased cell sensitivity to radiation by inhibiting autophagy activation via the PI3K/AKT/mTOR signaling pathway. The present study provides a theoretical basis for a promising treatment for radioresistant NPC by inhibiting c-Jun expression.

| S-EPMC8339856 | biostudies-literature

Apatinib Inhibits Cell Proliferation and Induces Autophagy in Human Papillary Thyroid Carcinoma via the PI3K/Akt/mTOR Signaling Pathway.

Project description:Background: Patients with metastatic radioiodine-refractory papillary thyroid carcinoma (PTC) have limited treatment options and a poor prognosis. There is an urgent need to develop new drugs targeting PTC for clinical application. Apatinib, a novel small-molecule tyrosine kinase inhibitor (TKI), is highly selective for vascular endothelial growth factor receptor-2 (VEGFR2) and exhibits antitumor effects in a variety of solid tumors. Although apatinib has been shown to be safe and efficacious in radioiodine-refractory differentiated thyroid cancer, the mechanism underlying its antitumor effect is unclear. In this report, we explored the effects of apatinib on PTC in vitro and in vivo. Methods: VEGFR2 expression levels were evaluated by immunohistochemistry (IHC), qPCR, and western blotting (WB). The effects of apatinib on cell viability, colony formation, and migration in the Transwell assay were assessed in vitro, and its effect on tumor growth rate was assessed in vivo. In addition, the levels of proteins in signaling pathways were determined by WB. Finally, the autophagy level was assessed by WB, immunofluorescence (IF), and transmission electron microscopy. Results: We found that high VEGFR2 expression is associated with tumor size, T stage, and lymph node metastasis in patients with PTC and that apatinib inhibits PTC cell growth, promotes apoptosis, and induces cell cycle arrest through the PI3K/Akt/mTOR signaling pathway. Moreover, apatinib induces autophagy, and pharmacological inhibition of autophagy or small interfering RNA (siRNA)-mediated targeting of autophagy-associated gene 5 (ATG5) can further increase PTC cell apoptosis. Conclusion: Our data suggest that apatinib can induce apoptosis and autophagy via the PI3K/Akt/mTOR signaling pathway for the treatment of PTC and that autophagy is a potential novel target for future therapy in resistant PTC.

| S-EPMC7078169 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data