BMC Seminar Thursday 11 March at 12:00
Speaker: Linda Viðarsdóttir, postdoctoral research fellow at Cancer Research Laboratory, Faculty of Medicine, Sturlugata 8, University of Iceland
Title: PTENpg1 antisense RNA mediates PTEN suppression in vemurafenib resistance and predicts clinical outcome in melanoma patients
Abstract: Vemurafenib is a highly potent inhibitor of BRAFV600E and prolongs survival in ~80% of melanoma patients carrying the mutation. Unfortunately, almost all patients develop resistance within 6-8 months of starting treatment. A combination of BRAFV600E and loss of PTEN, including by epigenetic silencing, is a common event in melanomagenesis and drug resistance. A long non-coding RNA, PTENpg1as, is one of the main regulators of PTEN transcription and its role in melanoma has not yet been elucidated.
Here, we used a cell line model system that was generated by making the melanoma cell line A375 resistant to vemurafenib. Resistant cell lines showed increased PTENpg1 asRNA expression while PTEN expression was suppressed. Further, ChIP analysis showed enrichment of the histone modification enzyme EZH2 and subsequent enrichment of H3K27me3 at the PTEN promoter in the resistant cell line. siRNA co-knockdown of EZH2 and DNMT3a restored PTEN expression in the resistant A375 cells and the cells were resensitized to vemurafenib upon knockdown. In addition, we found that PTENpg1 asRNA expression is significantly increased in melanoma patients with short-term survival.
In this talk I will explain the function of the lncRNA PTENpg1 asRNA and its part in vemurafenib resistance and how it could be an attractive therapeutic target.