Back to Search
Start Over
BRAFi induced demethylation of miR-152-5p regulates phenotype switching by targeting TXNIP in cutaneous melanoma
- Source :
- Apoptosis. 25:179-191
- Publication Year :
- 2020
- Publisher :
- Springer Science and Business Media LLC, 2020.
-
Abstract
- Treatment of advanced BRAFV600-mutant melanoma using BRAF inhibitors (BRAFi) eventually leads to drug resistance and selects for highly metastatic tumor cells. We compared the most differentially dysregulated miRNA expression profiles of vemurafenib-resistant and highly-metastatic melanoma cell lines obtained from GEO DataSets. We discovered miR-152-5p was a potential regulator mediating melanoma drug resistance and metastasis. Functionally, knockdown of miR-152-5p significantly compromised the metastatic ability of BRAFi-resistant melanoma cells and overexpression of miR-152-5p promoted the formation of slow-cycling phenotype. Furthermore, we explored the cause of how and why miR-152-5p affected metastasis in depth. Mechanistically, miR-152-5p targeted TXNIP which affected metastasis and BRAFi altered the methylation status of MIR152 promoter. Our study highlights the crucial role of miR-152-5p on melanoma metastasis after BRAFi treatment and holds significant implying that discontinuous dosing strategy may improve the benefit of advanced BRAFV600-mutant melanoma patients.
- Subjects :
- Male
Proto-Oncogene Proteins B-raf
0301 basic medicine
Cancer Research
Skin Neoplasms
Clinical Biochemistry
Regulator
Pharmaceutical Science
Metastasis
03 medical and health sciences
0302 clinical medicine
Cell Movement
Cell Line, Tumor
Humans
Medicine
Neoplasm Metastasis
Promoter Regions, Genetic
Melanoma
Protein Kinase Inhibitors
Pharmacology
Gene knockdown
business.industry
Cell Cycle
Biochemistry (medical)
Cell Biology
Methylation
Middle Aged
medicine.disease
Phenotype
Demethylation
Gene Expression Regulation, Neoplastic
MicroRNAs
030104 developmental biology
Vemurafenib
Drug Resistance, Neoplasm
030220 oncology & carcinogenesis
Mutation
Cutaneous melanoma
Cancer research
Female
Carrier Proteins
business
TXNIP
Subjects
Details
- ISSN :
- 1573675X and 13608185
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Apoptosis
- Accession number :
- edsair.doi.dedup.....e44090fc5f28075f95dd4fa3490adf55