Epigenetic silencing of miR-144/451a cluster contributes to HCC progression via paracrine HGF/MIF-mediated TAM remodeling.

ABSTRACT:

Background & aims

Hepatocellular carcinoma (HCC) is among the malignancies with the highest mortality. The key regulators and their interactive network in HCC pathogenesis remain unclear. Along with genetic mutations, aberrant epigenetic paradigms, including deregulated microRNAs (miRNAs), exert profound impacts on hepatocyte transformation and tumor microenvironment remodeling; however, the underlying mechanisms are largely uncharacterized.

Methods

We performed RNA sequencing on HCC specimens and bioinformatic analyses to identify tumor-associated miRNAs. The miRNA functional targets and their effects on tumor-infiltrating immune cells were investigated. The upstream events, particularly the epigenetic mechanisms responsible for miRNA deregulation in HCC, were explored.

SUBMITTER: Zhao J 

PROVIDER: S-EPMC7927270 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature