CircAkt3 participates in bone cancer pain progression in rats by modulating MAPK signalling pathway
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE224395 | GEO | 2024/02/01
REPOSITORIES: GEO
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Project description:CircRNA parent genes were mainly enriched in MAPK and neurodevelopmental signalling pathways. CircAkt3 and circMap4k1 were significantly up-regulated in the bone cancer pain group. CircaAkt3 may increase p-ERK expression by upregulating Col8a1, which may further activate the MAPK pathway.
2023-02-14 | GSE224978 | GEO
Project description:CircAkt3 participates in bone cancer pain progression in rats by modulating MAPK signalling pathway
| PRJNA933211 | ENA
Project description:CircAkt3 participates in bone cancer pain progression in rats by modulating MAPK signalling pathway
| PRJNA930768 | ENA
Project description:In hepatocellular carcinoma (HCC) development, cancer cells generally exhibit increased cell proliferation due to mutations and aberrant expressions of key regulatory genes. The current study determines the cytotoxic effects of β-caryophyllene (BCP) alone or in combination with doxorubicin (DOX) and cisplatin (DDP) on HCC cells and also elucidates the underlying mechanism of BCP to exert its anticancer activities. HepG2, SMMC-7721 HCC cells, and HL-7702 normal liver cells were treated with BCP, DOX, and DDP individually or in their combinations. Cell proliferation assay, flow cytometric assay, and Western blot analysis were used to evaluate the cytotoxic effects of these treatments. Transwell assays were used to examine the effects of BCP on migration and invasion of HCC cells. RNA-seq studies were used to determine the primary target genes of BCP-treated HepG2 cells. Integrative analysis of differentially expressed genes (DEGs) of RNA-seq data with a TCGA dataset of HCC patients identified BCP-targeted genes that were verified by RT-qPCR. Ectopic gene expression, cell viability, and colony formation assay were performed to validate the primary targets of BCP. The results found that, BCP selectively inhibited HCC cell proliferation while exhibited relatively low toxicity to normal liver cells; however, DOX and DDP showed higher toxicity in normal cells than that in HCC cells. Importantly, in combinatorial treatments, BCP synergistically enhanced cytotoxicity of DOX and DDP in HCC cells but this effect is markedly reduced in HL-7702 cells. BCP-treated HCC cells exhibited decreased migration and invasion ability versus the control. Furthermore, RNA-seq analyses of BCP-treated HepG2 cells identified 433 protein-coding DEGs with over 1.5-fold change. Integrative analyses revealed five BCP-targeted DEGs regulating the MAPK signaling pathway. Among these five genes, three displayed a significantly positive correlation of their expression with the overall survival of HCC patients. As a primary target, PGF was significantly downregulated by BCP treatment, and its exogenous expression desensitized HCC cells to the inhibition of BCP treatment. In summary, BCP inhibits malignant properties of HCC and synergistically sensitizes the anticancer activity of DOX and DDP. In HCC cells, BCP primarily targets PGF and MAPK signaling pathway.
2024-09-03 | GSE276099 | GEO
Project description:Objectives: This study aimed to identify a set of differentially expressed genes (DEGs) in dorsal root ganglions (DRGs) between bone cancer pain (BCP) and sham BCP rats using RNA-sequencing (RNA-Seq). Methods: We established a rat BCP model by implanting MRMT-1 cells into the bone marrow cavity of left tibia. RNA-Seq was used to screen related genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis and protein-protein interaction (PPI) network analysis were conducted to investigate the bioinformatics functions of DEGs and possible potential pathological mechanisms of BCP. Results: RNA-Seq of ipsilateral DRGs from model rats identified a total of 152 DEGs compared to sBCP rats. The expression changes of four randomly selected DEGs were verified by qPCR. Four significant signaling pathways have been found for BCP including MAPK signaling pathway, calcium signaling pathway, apelin signaling pathway and oxytocin signaling pathway. Cxcl13 in DRGs was identified as a key player in the BCP model by comparing with published datasets in classic pain models. A core set of genes contributed to BCP mechanism were sorted out by PPI network analysis. Conclusions: These altered mRNAs and signaling pathways might be potential therapeutic targets for BCP treatment, which can guide future research on the molecular mechanism of BCP.
2023-12-12 | GSE249443 | GEO
Project description:Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced-stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle-related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl-2 and Bcl-xL) and upregulation of pro-apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase-mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro-apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC.
| S-EPMC10826427 | biostudies-literature
Project description:The close integration of the MAPK, PI3K and WNT signaling pathways underpins much of development and is deregulated in cancer. In principle, combinatorial post-translational modification of key lineage–specific transcription factors would be an effective means to integrate critical signaling events. Understanding how this might be achieved is central to deciphering the impact of microenvironmental cues in development and disease. The microphthalmia associated transcription factor, MITF, plays a crucial role in the development of melanocytes, the retinal pigment epithelium, osteoclasts and mast cells, and acts as a lineage survival oncogene in melanoma. MITF coordinates survival, differentiation, cell cycle progression, cell migration, metabolism and lysosome biogenesis. Yet how the activity of this key transcription factor is controlled remains poorly understood. Here we show that GSK3b, downstream from both the PI3K and Wnt pathways, and BRAF/MAPK signaling converge to control MITF nuclear export. Phosphorylation of the melanocyte MITF-M isoform in response to BRAF/MAPK signaling primes for phosphorylation by GSK3b, a kinase inhibited by both PI3K and Wnt signaling. Dual phosphorylation, but not monophosphorylation, then promotes MITF nuclear export by activating a previously unrecognized hydrophobic export signal. Nonmelanocyte MITF isoforms exhibit poor regulation by MAPK signaling, but instead their export is controlled by mTOR. We uncover here an unanticipated mode of MITF regulation that integrates the output of key developmental and cancer-associated signaling pathways to gate MITF flux through the import-export cycle. The results have significant implications for our understanding of melanoma progression and stem cell renewal
2022-02-28 | PXD010665 | Pride
Project description:To investigate the function of COL8A1 in GSCs progression, we established U251-COL8A1 cell lines with COL8A1 overexpressed. Then we performed gene expression profiling analysis using data obtained from RNA-seq of 2 cells (U251NC and U251-COL8A1)
2024-07-01 | GSE246528 | GEO
Project description:Background and purposeThe development of antinociceptive morphine tolerance is a clinically intractable problem. Earlier work has demonstrated the pivotal roles of PDGF and its receptor PDGFRβ in morphine tolerance. Here, we have investigated the role of spinal heat shock protein 27 (HSP27) in morphine tolerance and its relationship with PDGFRβ activation.Experimental approachRats were treated with morphine for 9 days, and its anti-nociceptive effect against thermal pain was evaluated by a tail-flick latency test. Western blot, real-time PCR, immunofluorescent staining, and various antagonists, agonists, and siRNA lentiviral vectors elucidated the roles of HSP27, PDGFRβ, and related signalling pathways in morphine tolerance.Key resultsChronic morphine administration increased expression and phosphorylation of HSP27 in the spinal cord. Down-regulating HSP27 attenuated the development of morphine tolerance. PDGFRβ antagonism inhibited HSP27 activation and attenuated and reversed morphine tolerance. PDGFRβ induction increased HSP27 expression and activation and partly decreased morphine analgesia. PDGFRβ inhibition reduced Akt and p38 MAPK activity in morphine tolerance. PI3K and p38 inhibitors reversed morphine tolerance and suppressed morphine-induced HSP27 phosphorylation.Conclusion and implicationsThis study demonstrated for the first time that spinal HSP27 participates in PDGFRβ-mediated morphine tolerance via the PI3K/Akt and p38 MAPK signalling pathways. These findings suggest a potential clinical strategy for prolonging the antinociceptive effects of opioids during long-term pain control.
| S-EPMC7589020 | biostudies-literature