Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Small ribosomal protein subunit S7 suppresses ovarian tumorigenesis through regulation of the PI3K/AKT and MAPK pathways.

ABSTRACT: Small ribosomal protein subunit S7 (RPS7) has been reported to be associated with various malignancies, but the role of RPS7 in ovarian cancer remains unclear. In this study, we found that silencing of RPS7 by a specific shRNA promoted ovarian cancer cell proliferation, accelerated cell cycle progression, and slightly reduced cell apoptosis and response to cisplatin treatment. Knockdown of RPS7 resulted in increased expression of P85α, P110α, and AKT2. Although the basal levels of ERK1/2, MEK1/2, and P38 were inconsistently altered in ovarian cancer cells, the phosphorylated forms of MEK1/2 (Ser217/221), ERK1/2 (Thr202/Tyr204), JNK1/2 (Thr183/Tyr185), and P38 (Thr180/Tyr182) were consistently reduced after RPS7 was silenced. Both the in vitro anchorage-independent colony formation and in vivo animal tumor formation capability of cells were enhanced after RPS7 was depleted. We also showed that silencing of RPS7 enhanced ovarian cancer cell migration and invasion. In sum, our results suggest that RPS7 suppresses ovarian tumorigenesis and metastasis through PI3K/AKT and MAPK signal pathways. Thus, RPS7 may be used as a potential marker for diagnosis and treatment of ovarian cancer.

SUBMITTER: Wang Z

PROVIDER: S-EPMC3823983 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Erianin suppresses hepatocellular carcinoma cells through down-regulation of PI3K/AKT, p38 and ERK MAPK signaling pathways.

Project description:BACKGROUND:Hepatocellular carcinoma (HCC) is the dominant pathological type of primary liver cancer and no effective methods are available for its treatment. Erianin is a natural product extracted from Dendrobium, which possesses multiple pharmacological activities, including antioxidative and antitumor activity. OBJECTIVE:To evaluate the anti-HCC activities of erianin and explore its underlying mechanism. METHODS:MTT assay and Crystal Violet staining assay were used to select the non-toxic concentrations for the subsequent experiments. The colony formation assay and PCNA fluorescent staining were used to investigate the antiproliferative effects of erianin on human SMMC-7721 and HepG2 cells. Wound healing and transwell test were used to analyze cell migration and invasion. Caspase3 and Tunel staining were used to detect apoptosis. Western blot was used to examine the expression levels of proteins associated with invasion and key proteins in the phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt), p38 and ERK mitogen-activated protein kinase (MAPK) signaling pathways. RESULTS:Erianin inhibited HCC cell proliferation in a dose-dependent manner. Decreased migration rate and invaded cells were observed with erianin supplement. The expression of invasion-associated proteins in the erianin group was also down-regulated. Besides, more apoptotic cells were observed after erianin treatment. For the molecular mechanism, erianin inhibited the phosphorylation of Akt, ERK and P38 in the PI3K/Akt and ERK/P38 pathway. CONCLUSION:We demonstrated, for the first time, that erianin inhibited the proliferation, migration, invasion and induced the apoptosis of HCC through PI3K/Akt, p38 and ERK MAPK signaling pathway, indicating that erianin is a promising agent for the HCC treatment.

| S-EPMC7385585 | biostudies-literature

Assembly of the 30S ribosomal subunit: positioning ribosomal protein S13 in the S7 assembly branch.

Project description:Studies of Escherichia coli 30S ribosomal subunit assembly have revealed a hierarchical and cooperative association of ribosomal proteins with 16S ribosomal RNA; these results have been used to compile an in vitro 30S subunit assembly map. In single protein addition and omission studies, ribosomal protein S13 was shown to be dependent on the prior association of ribosomal protein S20 for binding to the ribonucleoprotein particle. While the overwhelming majority of interactions revealed in the assembly map are consistent with additional data, the dependency of S13 on S20 is not. Structural studies position S13 in the head of the 30S subunit > 100 A away from S20, which resides near the bottom of the body of the 30S subunit. All of the proteins that reside in the head of the 30S subunit, except S13, have been shown to be part of the S7 assembly branch, that is, they all depend on S7 for association with the assembling 30S subunit. Given these observations, the assembly requirements for S13 were investigated using base-specific chemical footprinting and primer extension analysis. These studies reveal that S13 can bind to 16S rRNA in the presence of S7, but not S20. Additionally, interaction between S13 and other members of the S7 assembly branch have been observed. These results link S13 to the 3' major domain family of proteins, and the S7 assembly branch, placing S13 in a new location in the 30S subunit assembly map where its position is in accordance with much biochemical and structural data.

| S-EPMC1370675 | biostudies-literature

Computational Modeling of PI3K/AKT and MAPK Signaling Pathways in Melanoma Cancer.

Project description:BACKGROUND:Malignant melanoma is an aggressive tumor of the skin and seems to be resistant to current therapeutic approaches. Melanocytic transformation is thought to occur by sequential accumulation of genetic and molecular alterations able to activate the Ras/Raf/MEK/ERK (MAPK) and/or the PI3K/AKT (AKT) signalling pathways. Specifically, mutations of B-RAF activate MAPK pathway resulting in cell cycle progression and apoptosis prevention. According to these findings, MAPK and AKT pathways may represent promising therapeutic targets for an otherwise devastating disease. RESULT:Here we show a computational model able to simulate the main biochemical and metabolic interactions in the PI3K/AKT and MAPK pathways potentially involved in melanoma development. Overall, this computational approach may accelerate the drug discovery process and encourages the identification of novel pathway activators with consequent development of novel antioncogenic compounds to overcome tumor cell resistance to conventional therapeutic agents. The source code of the various versions of the model are available as S1 Archive.

| S-EPMC4807832 | biostudies-literature

An optically active isochroman-2H-chromene conjugate potently suppresses neuronal oxidative injuries associated with the PI3K/Akt and MAPK signaling pathways.

Project description:Increasing evidence suggests that the use of potent neuroprotective agents featured with novel pharmacological mechanism would offer a promising strategy to delay or prevent the progression of neurodegeneration. Here, we provide the first demonstration that the chiral nonracemic isochroman-2H-chromene conjugate JE-133, a novel synthetic 1,3-disubstituted isochroman derivative, possesses superior neuroprotective effect against oxidative injuries. Pretreatment with JE-133 (1-10 μM) concentration-dependently prevented H2O2-induced cell death in SH-SY5Y neuroblastoma cells and rat primary cortical neurons. Pretreatment with JE-133 significantly alleviated H2O2-induced apoptotic changes. These protective effects could not be simply attributed to the direct free radical scavenging as JE-133 had moderate activity in reducing DPPH free radical. Further study revealed that pretreatment with JE-133 (10 μM) significantly decreased the phosphorylation of MAPK pathway proteins, especially ERK and P38, in the neuronal cells. In addition, blocking PI3K/Akt pathway using LY294002 partially counteracted the cell viability-enhancing effect of JE-133. We conclude that JE-133 exerts neuroprotection associated with dual regulative mechanisms and consequently activating cell survival and inhibiting apoptotic changes, which may provide important clues for the development of effective neuroprotective drug lead/candidate.

| S-EPMC7921582 | biostudies-literature

Inotilone from Inonotus linteus suppresses lung cancer metastasis in vitro and in vivo through ROS-mediated PI3K/AKT/MAPK signaling pathways.

Project description:Metastasis is one of the main causes of mortality in cancer patients. Inotilone, a major component of Inonotus linteus, is a traditional Chinese medical herb. In this study, MTT results showed that inotilone had no obvious cytotoxicity. Animal model results revealed that inotilone suppressed cancer metastatic efficacy. Serum results showed that inotilone reduced the activity of matrix metalloproteinase (MMP)-2 and -9 and tumor necrosis factor alpha (TNF-α) activity as well as NO content. Additionally, inotilone affected MMP-9 and tissue inhibitor of metalloproteinase (TIMP)-2 protein expression and improved the activity of the antioxidant enzymes in the lung tissues of LLC-bearing mice. In addition, cell experimental results showed that inotilone reduced the activity of MMP-2/-9 and inhibited the ability for cellular migration and invasion. Inotilone decreased interleukin (IL)-8 expression in A549 cells. Western blot results revealed that inotilone affected the protein expression of MMPs, nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, anti-oxidant enzymes, mitogen activated protein kinase (MAPK), focal adhesion kinase (FAK), phosphoinositide-3 kinase (PI3K)-AKT, and nuclear factor (NF)κB. Therefore, we propose that inotilone is a potential therapeutic candidate against metastatic lung cancer cells.

| S-EPMC6382761 | biostudies-literature

GLUD1 suppresses renal tumorigenesis and development <i>via</i> inhibiting PI3K/Akt/mTOR pathway.

Project description:Growing cancer cells are addicted to glutamine. Glutamate dehydrogenase 1 (GLUD1) is one of key enzymes in glutamine metabolism and plays a critical role in the malignancy of diverse tumors. However, its role and molecular mechanism in clear cell renal cell carcinoma (ccRCC) development and progression remain unknown. In this study, analysis results of the GEO/TCGA/UALCAN database showed that GLUD1 level was downregulated in ccRCC tissues. Immunohistochemistry and western blotting results further validated the downregulation of GLUD1 level in ccRCC tissues. GLUD1 level was gradually decreased as ccRCC stage and grade progressed. Low GLUD1 level was associated with a shorter survival and higher IC50 value for tyrosine kinase inhibitors (TKIs) in ccRCC, reminding that GLUD1 level could predict the prognosis and TKIs sensitivity of ccRCC patients. High level of methylation in GLUD1 promoter was positively correlated with the downregulation of GLUD1 level and was negatively correlated with survival of ccRCC patients. GLUD1 overexpression suppressed RCC cell proliferation, colony formation and migration by inhibiting PI3K/Akt/mTOR pathway activation. Low GLUD1 level correlated with suppressive immune microenvironment (TIME) in ccRCC. Together, we found a novel tumor-suppressing role of GLUD1 in ccRCC which was different from that in other tumors and a new mechanism for inhibiting PI3K/Akt/mTOR activation and TIME in ccRCC. These results provide a theoretical basis for GLUD1 as a therapeutic target and prognostic marker in ccRCC.

| S-EPMC9530280 | biostudies-literature

Qilin Pill Exerts Therapeutic Effect on Resection-Induced Premature Ovarian Insufficiency Rats by Inhibiting the MAPK and PI3K-AKT Signaling Pathways.

Project description:BackgroundThe Qilin pill (QLP) is a traditional Chinese compound prescription comprising 15 herbs that has demonstrated significant therapeutic effects on premature ovarian insufficiency (POI) in recent years. However, a pharmacological evaluation of QLP on ovarian function remains to be conducted, and the key mechanism of QLP treatment on POI is unclear.MethodsPremature ovarian insufficiency rats were established by bilateral partial ovariectomy. The model rats were administrated with low (QLP-L), medium (QLP-M) and high (QLP-H) doses of QLP for 4 weeks to evaluate the ovarian function in terms of estrous cycle, hormone level, and follicle count. The mechanism of QLP in the treatment of POI was systematically explored by network pharmacology, and expression levels of the MAPK and PI3K-AKT signaling pathways were verified by Western blotting and molecular docking.ResultsThe rat model of resection-induced POI was successfully established, and QLP could significantly recover the estrous cycle, decrease serum FSH levels, and decelerate follicle depletion after 4 weeks of administration. The optimal dose of QLP in the experiment was preliminarily determined to be 0.9 g/kg. Based on the network pharmacology methods, we constructed the compound-target network and protein protein interaction (PPI) network of QLP for the treatment of POI. The experimental verification of the enrichment analysis showed that QLP inhibited the MAPK and PI3K-AKT signaling pathways, and the key compounds and key targets involved were verified by molecular docking.ConclusionQLP exerted significant therapeutic effects on resection-induced POI rats, and this was achieved by the inhibition of the MAPK and PI3K-AKT signaling pathways. This study is the first to systematically investigate the effects and mechanism of QLP on POI rats, which will provide valuable guidance in clinic.

| S-EPMC8331109 | biostudies-literature

YWHAE as an HE4 interacting protein can influence the malignant behaviour of ovarian cancer by regulating the PI3K/AKT and MAPK pathways.

Project description:BackgroundMalignant tumours of the female reproductive system threaten the lives and health of women worldwide, with ovarian cancer having the highest mortality rate. Based on previous work, this study analysed the expression and role of YWHAE in ovarian epithelial tumours.MethodsThe interaction between YWHAE and HE4 was evaluated via immunoprecipitation, western blot analysis, and cellular immunofluorescence. Immunohistochemistry was used to address the relationship between YWHAE expression, clinicopathological parameters, and patient prognosis. Changes in cell invasion, epithelial-mesenchymal transition, migration, proliferation, apoptosis, and cell cycle before and after differential expression of YWHAE were also explored in ovarian cancer cell lines and via in vivo experiments.ResultsYWHAE was found to interact with HE4, and its expression was positively correlated with HE4 expression. Moreover, YWHAE upregulation was associated with advanced stages of ovarian cancer and poor patient prognosis. In addition, YWHAE enhanced invasion, migration, and proliferation, but inhibited the apoptosis of ovarian cancer cells. These biological effects were found to be mediated by the AKT and MAPK signalling pathways.ConclusionsAltogether, this study demonstrates that YWHAE is substantially upregulated in ovarian cancer tissues, representing a risk factor for the prognosis of ovarian cancer that is positively correlated with HE4 expression. Furthermore, YWHAE and its downstream pathways may represent new therapeutic targets for ovarian cancer.

| S-EPMC8190858 | biostudies-literature

Regulation of dendritic morphogenesis by Ras-PI3K-Akt-mTOR and Ras-MAPK signaling pathways.

Project description:Dendritic arborization and spine formation are critical for the functioning of neurons. Although many proteins have been identified recently as regulators of dendritic morphogenesis, the intracellular signaling pathways that control these processes are not well understood. Here we report that the Ras-phosphatidylinositol 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway plays pivotal roles in the regulation of many aspects of dendrite formation. Whereas the PI3K-Akt-mTOR pathway alone controlled soma and dendrite size, a coordinated activation together with the Ras-mitogen-activated protein kinase signaling pathway was required for increasing dendritic complexity. Chronic inhibition of PI3K or mTOR reduced soma and dendrite size and dendritic complexity, as well as density of dendritic filopodia and spines, whereas a short-term inhibition promoted the formation of mushroom-shaped spines on cells expressing constitutively active mutants of Ras, PI3K, or Akt, or treated with the upstream activator BDNF. Together, our data underscore the central role of a spatiotemporally regulated key cell survival and growth pathway on trophic regulation of the coordinated development of dendrite size and shape.

| S-EPMC6725910 | biostudies-literature

CK-3, A Novel Methsulfonyl Pyridine Derivative, Suppresses Hepatocellular Carcinoma Proliferation and Invasion by Blocking the PI3K/AKT/mTOR and MAPK/ERK Pathways.

Project description:Hepatocellular carcinoma (HCC) is an aggressive tumor with a poor prognosis that highly expresses phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (ERK). The PI3K/AKT/mTOR and MAPK/ERK signaling pathways play a crucial role in HCC tumor formation, cell cycle, apoptosis and survival. However, no effective targeted therapies against these pathways is available, mainly due to the extensive and complex negative feedback loops between them. Here we used CK-3, a dual blocker of the PI3K/AKT/mTOR and MAPK/ERK pathways, against HCC cell lines to verify its anti-tumor activity in vitro. CK-3 exhibited cytotoxic activity against HCC, as demonstrated with MTT and colony formation assays. The anti-metastatic potential of CK-3 was demonstrated with wound healing and cell invasion assays. The ability of CK-3 to block both the PI3K/AKT/mTOR and MAPK/ERK pathways was also confirmed. CK-3 induced the apoptosis of Hep3B cells, while Bel7402 cells died via mitotic catastrophe (MC). Oral administration of CK-3 also inhibited the subcutaneous growth of BEL7402 cells in nude mice. Simultaneous PI3K/AKT/mTOR and MAPK/ERK pathway inhibition with CK-3 may be superior to single pathway monotherapies by inhibiting their feedback-regulation, and represents a potential treatment for HCC.

| S-EPMC8355706 | 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