The roles of mutated SWI/SNF complexes in the initiation and development of hepatocellular carcinoma and its regulatory effect on the immune system: A review

Abstract

Hepatocellular carcinoma (HCC) is a primary liver malignancy with a high global prevalence and a dismal prognosis. Studies are urgently needed to examine the molecular pathogenesis and biological characteristics of HCC. Chromatin remodelling, an integral component of the DNA damage response, protects against DNA damage‐induced genome instability and tumorigenesis by triggering the signalling events that activate the interconnected DNA repair pathways. The SWI/SNF complexes are one of the most extensively investigated adenosine triphosphate‐dependent chromatin remodelling complexes, and mutations in genes encoding SWI/SNF subunits are frequently observed in various human cancers, including HCC. The mutated SWI/SNF complex subunits exert dual functions by accelerating or inhibiting HCC initiation and progression. Furthermore, the abnormal SWI/SNF complexes influence the transcription of interferon‐stimulated genes, as well as the differentiation, activation and recruitment of several immune cell types. In addition, they exhibit synergistic effects with immune checkpoint inhibitors in the treatment of diverse tumour types. Therefore, understanding the mutations and deficiencies of the SMI/SNF complexes, together with the associated functional mechanisms, may provide a novel strategy to treat HCC through targeting the related genes or modulating the tumour microenvironment.

Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg

“… 36 Epigenetic alterations involving the chromatin remodelling machinery and ncRNAs have recently been reviewed elsewhere. [37] , [38] , [39] Herein, we review basic epigenetic mechanisms and the role of their dysregulation on hepatocarcinogenesis, focusing on DNA methylation and histone PTMs. We also highlight emerging strategies for the molecular targeting of epigenetic mechanisms with so-called “epidrugs” in HCC treatment and prevention.…”

Prognostic Value of PLXND1 and TGF-β1 Coexpression and Its Correlation With Immune Infiltrates in Hepatocellular Carcinoma

“…More than 70% of patients are diagnosed at an advanced stage with a dismal prognosis. Surgical resection and chemotherapy are the conventional treatment for HCC, but the mortality rate of this cancer remains high ( 4 ). In recent years, immunotherapy is increasingly considered as one of the most promising approaches for identifying drug targets for therapeutic interventions ( 5 , 6 ).…”

NEAT1 and Paraspeckles in Cancer Development and Chemoresistance

“…Similarly, the other paraspeckle proteins also have diverse functions. For instance, P54 nrb and SWI are complex nuclear proteins involved in many processes [ 10 , 11 ]. However, in the case of these proteins, the ways their sequestration affects cancer development is as yet unknown.…”