Normalization of the ATP1A1 Signalosome Rescinds Epigenetic Modifications and Induces Cell Autophagy in Hepatocellular Carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. In metabolic dysfunction-associated steatohepatitis (MASH)-related HCC, cellular redox imbalance from metabolic disturbances leads to dysregulation of the α1-subunit of the Na/K-ATPase (ATP1A1) signalosome. We have recently reported that the normalization of this pathway exhibited tumor suppressor activity in MASH-HCC. We hypothesized that dysregulated signaling from the ATP1A1, mediated by cellular metabolic stress, promotes aberrant epigenetic modifications including abnormal post-translational histone modifications and dysfunctional autophagic activity, leading to HCC development and progression. Increased H3K9 acetylation (H3K9ac) and H3K9 tri-methylation (H3K9me3) were observed in human HCC ce

SUBMITTER: Rajan PK 

PROVIDER: S-EPMC10572209 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature