Correction to: ARNTL hypermethylation promotes tumorigenesis and inhibits cisplatin sensitivity by activating CDK5 transcription in nasopharyngeal carcinoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Peng H
PROVIDER: S-EPMC8780747 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BACKGROUND:Increasing evidence support an important role for DNA methylation in nasopharyngeal carcinoma (NPC). Here, we explored the role of circadian clock gene Aryl Hydrocarbon Receptor Nuclear Translocator-Like (ARNTL) methylation in NPC. METHODS:We employed bisulfite pyrosequencing to determine the epigenetic change of ARNTL in NPC cell lines and tissues. ARNTL mRNA and protein expression in cell lines and tissues were detected by real-time PCR and western blotting. Then, we constructed cell lines overexpressing ARNTL and knocked down ARNTL to explore its function and effect on chemotherapy sensitivity of NPC cell lines to cisplatin in vitro and vivo. Finally, we investigated the potential molecular mechanism of ARNTL by gene set enrichment analysis (GSEA), dual Luciferase reporter assay and chromatin immunoprecipitation assay. RESULTS:ARNTL was hypermethylated, and its mRNA and protein were significantly down-regulated in NPC cell lines and tissues. When treated by 5-aza-2'-deoxycytidine, mRNA expression was up-regulated. Overexpression of ARNTL could suppress NPC cells proliferation in vitro and vivo while silencing of ARNTL using shRNA achieved opposite results. GSEA assay found that ARNTL was associated with cell cycle and ectopic ARNTL overexpression could induce G2-M phase arrest. Then, we identified and validated cyclin-dependent kinase 5 (CDK5) as the targeting gene of ARNTL by dual Luciferase reporter assay and chromatin immunoprecipitation assay. When transiently infected ARNTL-overexpression cells with PENTER-vector or PENTER-CDK5 plasmids, the later could reverse the suppressive effects of ARNTL on NPC cell proliferation. Moreover, ARNTL significantly enhanced sensitivity to cisplatin in NPC cells. CONCLUSIONS:ARNTL suppresses NPC cell proliferation and enhances sensitivity to cisplatin by targeting CDK5. ARNTL may represent a novel therapeutic target for NPC.
| S-EPMC6325889 | biostudies-other
Project description:BackgroundNasopharyngeal carcinoma (NPC) is a poorly differentiated malignant tumor, and 5-fluorouracil (5-FU) is one of the most effective chemotherapeutic drugs used for the treatment of NPC. Abnormal expression of RGS17 had been shown to improve the sensitivity of many cancers to chemotherapy; however, the effects of RGS17 on NPC remain unclear.MethodsWe cultured NPC cell lines and altered the RGS17 expression with vector. Subsequently colony formation assays and CCK8 cell viability assay was used to test the proliferation of NPC cells, flow cytometry was used to determine the percentage of apoptotic cells, MMP kit and flow cytometry was used to measure the mitochondrial membrane potential, and a xenograft tumour model was attached to investigate the effects of RGS17 on the growth of NPC cells in vivo. Additionally, RT-PCR and western blot was induced to examine the expression of RGS17 and the mechanism.ResultsHere, we report for the first time that RGS17 is downregulated in NPC cell lines and that RGS17 overexpression significantly reduces cell proliferation, decreases the mitochondrial membrane potential, and induces cell apoptosis in NPC cells. In vivo, RGS17 also inhibits the tumorigenicity of NPC. In addition, RGS17 could significantly improve the sensitivity of NPC cells to 5-FU. Furthermore, investigation into the underlying mechanisms showed that RGS17 upregulated the levels of IRE1α, p53, and active caspase-3 and cleaved PARP.ConclusionThese results indicate that RGS17 could play important roles in the proliferation, apoptosis, and chemotherapeutic sensitivity of NPC cells.
| S-EPMC6223391 | biostudies-literature
Project description:Transcriptional profiling of cisplatin sensitive NPCs 6-condition experiment, CNE2 vs. S16 cells at 0, 2 or 8 hr treatment. Biological replicates: 2 for each control (0 hr), 2 for each treatment (2 hr and 8 hr), independently grown and harvested, dye-swapped.
2013-08-13 | E-GEOD-49813 | biostudies-arrayexpress
Project description:Transcriptional profiling of cisplatin sensitive NPCs
2013-08-13 | GSE49813 | GEO
Project description:Nasopharyngeal carcinoma (NPC) is characterized by a high rate of local invasion and early distant metastasis. Increasing evidence indicates that epigenetic abnormalities play important roles in NPC development. However, the epigenetic mechanisms underlying NPC metastasis remain unclear. Here we investigate aberrantly methylated transcription factors in NPC tissues, and we identify the HOP homeobox HOPX as the most significantly hypermethylated gene. Consistently, we find that HOXP expression is downregulated in NPC tissues and NPC cell lines. Restoring HOPX expression suppresses metastasis and enhances chemosensitivity of NPC cells. These effects are mediated by HOPX-mediated epigenetic silencing of SNAIL transcription through the enhancement of histone H3K9 deacetylation in the SNAIL promoter. Moreover, we find that patients with high methylation levels of HOPX exhibit poor clinical outcomes in both the training and validation cohorts. In summary, HOPX acts as a tumour suppressor via the epigenetic regulation of SNAIL transcription, which provides a novel prognostic biomarker for NPC metastasis and therapeutic target for NPC treatment.
| S-EPMC5296651 | biostudies-literature
Project description:DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo. We further established that the tumor suppressor effect of NFAT1 is mediated by its inactivation of ITGA6 transcription. Our findings suggest the significance of activating NFAT1/ITGA6 signaling in aggressive NPC, defining a novel critical signaling mechanism that drives NPC invasion and metastasis and providing a novel target for future personalized therapy.
| S-EPMC6378632 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC), a subclass of cancers of the neck and head, is a predominant cause of cancer-associated death worldwide. Hence, there is a critical need for research into NPC-related treatment strategies. Cisplatin is a promising therapy option for NPCs and other cancers that is frequently utilized. Some patients acquire resistance to cisplatin therapy, which complicates the successful use of cisplatin treatment in NPCs. Although exosomal transfer of oncogenic miRNAs has been shown to improve recipient cell proliferation, metastasis and chemoresistance, the molecular mechanism behind this effect on NPC has yet to be fully understood. Exosomal microRNAs (miRNAs) from cisplatin-resistant cells were identified as significant mediators of chemoresistance in NPC cells in this investigation. Initially, we found that exosomal miR-106a-5p levels in the serum of chemoresistant and last-cycle patients were greater than in that of non-resistant and first-cycle patients. Also, exosomal miR-106a-5p enhanced the proliferative ability of NPC cells. Mechanistically, exosomal miR-106a-5p targets ARNT2, which further activates AKT phosphorylation, and thus promotes NPC cell proliferation, decreases apoptosis and in turn regulates tumorigenesis. We found similar results using in vivo NPC models, where exosomal miR-106a-5p through regulation of ARNT2 (aryl hydrocarbon receptor nuclear translocator 2) promoted tumorigenesis. Taken together, these findings indicate that exosomal miR-106a-5p could be a promising diagnostic biomarker and drug target for patients with NPC.
| S-EPMC8500979 | biostudies-literature
Project description:Chemotherapy forms the backbone of current treatments for many patients with advanced non-small-cell lung cancer (NSCLC). However, the survival rate is low in these patients due to the development of drug resistance, including cisplatin resistance. In this study, we developed a novel strategy to combat the growth of cisplatin-resistant (CR) NSCLC cells. We have shown that treatment with the plant-derived, non-psychotropic small molecular weight molecule, cannabidiol (CBD), significantly induced apoptosis of CR NSCLC cells. In addition, CBD treatment significantly reduced tumor progression and metastasis in a mouse xenograft model and suppressed cancer stem cell properties. Further mechanistic studies demonstrated the ability of CBD to inhibit the growth of CR cell lines by reducing NRF-2 and enhancing the generation of reactive oxygen species (ROS). Moreover, we show that CBD acts through Transient Receptor Potential Vanilloid-2 (TRPV2) to induce apoptosis, where TRPV2 is expressed on human lung adenocarcinoma tumors. High expression of TRPV2 correlates with better overall survival of lung cancer patients. Our findings identify CBD as a novel therapeutic agent targeting TRPV2 to inhibit the growth and metastasis of this aggressive cisplatin-resistant phenotype in NSCLC.
| S-EPMC8909073 | biostudies-literature
Project description:Nasopharyngeal carcinoma (NPC) is a high-risk head and neck cancer with poor clinical outcomes and insufficient treatments. The mouse double minute 2 homolog (MDM2) is the main molecular target in the clinical treatment of cancer. Indeed, MDM2 negatively regulates p53 through ubiquitin-dependent degradation. Thus, inhibition of MDM2-p53 interaction is a potential strategy for treating NPC. The latest generation MDM2 inhibitor, RG7388, shows increased potency and improved bioavailability compared to previous treatments. In this study, we investigated the efficacy and specificity of this inhibitor in NPC cell lines, and tumor-bearing mice were used to examine the therapeutic efficacy and effects of RG7388 treatment. The results showed that RG7388 potently decreased cell proliferation and activated p53-dependent pathway, resulting in cell cycle arrest and apoptosis. RG7388 significantly inhibited tumors in tumor-bearing mice. Activation of the p53 pathway-inhibited cell proliferation, as observed by detecting Ki67-positive cells. Additionally, the activity of apoptotic caspase family proteins was induced in the cleaved caspase-3-positive cells in vivo. Our results demonstrate that the MDM2 small-molecule inhibitor RG7388 is effective for NPC tumors, supporting further clinical investigation as a potential therapy for NPC.
| S-EPMC6783115 | biostudies-literature
Project description:Long noncoding RNA plasmacytoma variant translocation 1 (PVT1) plays pivotal roles in tumorigenesis of many cancers, including colorectal cancer (CRC). However, the clinical significance and the biological functions of PVT1 in CRC remain largely unknown. In this study, we found that PVT1 was highly expressed in CRC tissues and cell lines compared with the corresponding non-cancerous samples and normal colon epithelial cells. Clinically, increased expression of PVT1 was positively correlated with tumor size, advanced histological stages, metastases, poor prognosis, and cisplatin resistance of CRC patients. In vitro studies showed that PVT1 silencing inhibited the proliferation, migration, invasion, and apoptosis escape of CRC cells. Knockdown of PVT1 in cisplatin-resistant CRC cells induced proliferation inhibition and apoptosis, whereas overexpression of PVT1 increased proliferation and decreased apoptosis of CRC cells. Mechanically, the levels of drug resistance-associated molecules, including multidrug resistance 1 and multidrug resistance protein 1, as well as the expression of anti-apoptotic Bcl-2 were significantly downregulated whereas the levels of pro-apoptotic Bax and cleaved caspase-3 were increased in PVT1-silenced cisplatin-resistant CRC cells. However, ectopic expression of PVT1 in CRC cells reversed the expressions of the molecules mentioned above. In addition, PVT1 overexpression in CRC cells significantly promoted cisplatin resistance in vivo. Collectively, these results demonstrated that PVT1 is a significant regulator in tumorigenesis and cisplatin resistance of CRC and provided evidence that PVT1 may be a promising target for CRC therapy.
| S-EPMC5801353 | biostudies-other