Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Selamectin increases cisplatin sensitivity by inhibiting cisplatin-resistant genes expression and autophagy in uveal melanoma

ABSTRACT: Selamectin increases cisplatin sensitivity by inhibiting cisplatin-resistant genes expression and autophagy in uveal melanoma

PROVIDER: PRJNA949137 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Similar Datasets

Selamectin increases cisplatin sensitivity by inhibiting cisplatin-resistant genes expression and autophagy in uveal melanoma

Project description:Cisplatin resistance is the main reason for uveal melanoma (UM) treatment failure. Thus, developing strategy that increasing cisplatin sensitivity is needed. In this study, we performed drug repositioning analysis with the Connectivity Map database using a panel of previously identified cisplatin sensitivity–associated genes and cisplatin resistance–associated genes as the signature and obtained the antiparasitic drug selamectin. We demonstrated that the selamectin and cisplatin combination showed a synergistic effect on inhibiting UM cell growth. Experiments in tumor-bearing nude mice further showed that selamectin and cisplatin have synergistic effects in reducing tumor growth. Previous studies have linked increased autophagy with tumor resistance to chemotherapy. We found that selamectin inhibited the expression of the autophagy-related gene ATG9B, thus reducing autophagy. The cisplatin resistance–associated genes PDGFRB, DUSP1, MAST1 and IL11 were significantly downregulated in UM cells treated with selamectin. In summary, our study shows that selamectin enhanced the sensitivity of UM to cisplatin, through the mechanism of inhibiting cisplatin resistance–associated gene expression and autophagy. These findings may provide a new strategy for the treatment of UM.

2025-01-01 | GSE228250 | GEO

c-MYC-dependent transcriptional inhibition of autophagy is implicated in Cisplatin sensitivity in HPV-positive Head and Neck Cancer

Project description:Autophagy is important for removal, degradation and recycling of damaged organelles, proteins, and lipids through the degradative action of lysosomes. In addition to its catabolic function, autophagy is important in cancer and viral-mediated tumorigenesis, including Human Papillomavirus (HPV) positive cancers. HPV infection is a major risk factor in a subset of Head and Neck Cancer (HNC), for which no targeted therapies are currently available. Herein, we assessed autophagy function in HPV-positive HNC. We showed that HPV-positive HNC cells presented a transcriptional and functional impairment of autophagic process compared to HPV-negative cells, which was reactivated by knocking-down HPV E6/E7 oncoproteins, the drivers of cellular transformation. We found that the oncoprotein c-MYC was stabilized and triggered in HPV-positive cell lines. This resulted in the reduced binding of the MiT/TFE transcription factors to their autophagy targets due to c-MYC competition. Thus, knock-down of c-MYC induced the upregulation of autophagic and lysosomal genes in HPV-positive HNC cells, as well as the increase of autophagic markers at the protein level. Moreover, HPV oncoprotein E7 upregulated the expression of the phosphatase inhibitor CIP2A, accounting for c-MYC upregulation and stability in HPV+ HNC cells. CIP2A mRNA expression negatively correlated with autophagy gene expression in tumor tissues from HNC patients, showing, for the first time, its implication in a transcriptional autophagic context. Both CIP2A and c-MYC knock-down, as well as pharmacological downregulation of c-MYC, resulted in increased resistance to Cisplatin treatment. Our results not only show a novel way by which HPV oncoproteins manipulate the host machinery, but also provide more insights on the role of autophagy in chemoresistance, with possible implications for targeted HPV-positive HNC therapy.

2023-11-08 | GSE235662 | GEO

KLF6 alleviates hepatic ischemia-reperfusion injury by inhibiting autophagy

Project description:KLF6 alleviates hepatic ischemia-reperfusion injury by inhibiting autophagy

| PRJNA894155 | ENA

MiR-219-5p attenuates OC cisplatin resistance by inactivating Wnt/β-catenin signaling and autophagy via targeting HMGA2

Project description:To investigate the miR-219-5p decreases the resistance of OC cells to cisplatin via Wnt/β-catenin signaling and autophagy by regulating HMGA2, we tested the A2780 and A2780-DDP cell lines with miRNA-Seq.

2022-07-30 | GSE209922 | GEO

The STAT3 induced ITGB4 overexpression represses p53 to reduce the sensitivity of bladder cancer to cisplatin

Project description:Cisplatin-based chemotherapy is the first-line treatment for patients with advanced bladder cancer, but the development of cisplatin-resistance limits its anti-tumor effects. Previous studies have shown that cisplatin resistance in bladder cancer may be related to a variety of factors, such as changes in drug transport and metabolism, enhancement of DNA repair mechanisms, changes in cell cycle regulation, inhibition of apoptosis, and epigenetic modification. While, the mechanism of cisplatin resistance is still elusive.In this study, we first found that upregulated ITGB4 is correlated with poor prognosis after chemotherapy in bladder cancer. Next, we demonstrated ITGB4 plays a key role in regulating the sensitivity of bladder cancer to cisplatin therapy. Then, we found that ITGB4 reduced the sensitivity of bladder cancer to cisplatin by inhibiting p53-S15 site phosphorylation and promoting MDM2 binding to p53 to reduce p53 expression. In addition, we demonstrated that ITGB4 regulates the antitumor effects of MDM2 inhibitors combined with cisplatin therapy. Further, we found that ITGB4 was elevated in bladder cancer cisplatin-resistant cells, and the increase in ITGB4 was mediated by STAT3.The combination of STAT3 inhibitors can enhance the antitumor effect of cisplatin in bladder cancer.In summary, we identified ITGB4 as a key molecule affecting cisplatin sensitivity in bladder cancer, and proposed a strategy of combining drugs with STAT3 inhibitors to increase cisplatin sensitivity in bladder cancer.

2024-06-07 | GSE268855 | GEO

Inhibiting phosphatidylcholine remodeling in adipose tissue increases insulin sensitivity

Project description:Inhibiting phosphatidylcholine remodeling in adipose tissue increases insulin sensitivity

| PRJNA985667 | ENA

Cisplatin sensitivity in nasopharyngeal carcinoma cells (NPC)

Project description:Transcriptional profiling of cisplatin sensitive NPCs

2013-08-13 | GSE49813 | GEO

Cisplatin sensitivity in nasopharyngeal carcinoma cells (NPC)

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

Karyotyping using SNP array of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines MUM2B and OCM1A

Project description:Karyotyping by SNP array of primary uveal melanoma samples, uveal melanoma cell lines and normal controls The Human660WQuad v1.0 DNA Analysis Bead Chip and kit were used for high resolution molecular karyotyping of DNA isolated from snap-frozen primary uveal melanoma tissue isolated from enucleated eyes.

2013-02-14 | E-GEOD-44297 | biostudies-arrayexpress

Epigenome analysis of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines

Project description:Genome wide DNA methylation profiling of primary uveal melanoma cells, normal uveal melanocytes, neural crest stem cells, embryonic stem cells and uveal melanoma cell lines. The Illumina Infinium 27k Human DNA methylation Beadchip Rev B was used to obtain DNA methylation profiles across approximately 27,000 CpGs in the samples. Samples included 58 primary UM, 3 NUM and NCSC controls and 2 cell lines. Bisulphite converted DNA from the 63 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip Rev B

2013-02-14 | E-GEOD-44296 | biostudies-arrayexpress

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