NCOA5 deficiency promotes a unique liver protumorigenic microenvironment through p21^WAF1/CIP1 overexpression, which is reversed by metformin.

ABSTRACT: Prevention and treatment options for hepatocellular carcinoma (HCC) are presently limited, underscoring the necessity for further elucidating molecular mechanisms underlying HCC development and identifying new prevention and therapeutic targets. Here, we demonstrate a unique protumorigenic niche in the livers of Ncoa5^+/- mouse model of HCC, which is characterized by altered expression of a subset of genes including p21^WAF1/CIP1 and proinflammatory cytokine genes, increased putative hepatic progenitors, and expansions of activated and tissue-resident memory (TRM) CD8+ T lymphocytes, myeloid-derived suppressor cells (MDSCs), and alternatively activated M2 macrophages. Importantly, prophylactic metformin treatment reversed these characteristics including aberr

SUBMITTER: Williams M 

PROVIDER: S-EPMC7210077 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature