H3K27me3-mediated PGC1α gene silencing promotes melanoma invasion through WNT5A and YAP.

ABSTRACT: Oncogene-targeted and immune checkpoint therapies have revolutionized the clinical management of malignant melanoma and now offer hope to patients with advanced disease. Intimately connected to patients' overall clinical risk is whether the initial primary melanoma lesion will metastasize and cause advanced disease, but underlying mechanisms are not entirely understood. A subset of melanomas display heightened peroxisome proliferator-activated receptor γ coactivator 1-α (PGC1α) expression that maintains cell survival cues by promoting mitochondrial function, but also suppresses metastatic spread. Here, we show that PGC1α expression in melanoma cells was silenced by chromatin modifications that involve promoter H3K27 trimethylation. Pharmacological EZH2 inhibition diminished H3K27me3 histon

SUBMITTER: Luo C 

PROVIDER: S-EPMC6994149 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature