Dietary short-chain fatty acid Sodium Butyrate orchestrates pro-apoptotic and anti-angiogenic pathways in HCC cells by targeting the novel SND1/hTERT axis

Abstract

Hepatocellular Carcinoma (HCC) is the primary type of liver malignancy, which stands as the third leading contributor to cancer-related death worldwide. Its development is associated with multifactors, which include viral hepatitis, metabolic syndrome, lifestyle factors, and dysregulation of many genetic and epigenetic signalling pathways. MicroRNAs play the main role in gene regulation in eukaryotic cells, which functions primarily through RISC, and their dysregulations with enhanced expression of RNA-induced silencing complex (RISC) activity contribute to HCC pathogenesis. Staphylococcal nuclease domain-containing protein 1 (SND1), a core component of the RISC machinery, acts as an oncogene promoting tumor growth, invasion, and angiogenesis in HCC. Furthermore, aberrant telomerase activation, largely attributed to elevated expression of its catalytic subunit of human telomerase reverse transcriptase (hTERT), is a hallmark of approximately 90 % of cancers. Short-chain fatty acid (SCFA), Sodium Butyrate (NaBu), are gut microbiota-derived metabolites with emerging anti-cancer properties. NaBu acts as an HDAC inhibitor, exhibiting anti-proliferative, pro-apoptotic, and anti-inflammatory effects in various cancer models. In this study, we investigate the novel molecular mechanism by which NaBu regulates SND1 meditated hTERT expression in HCC and assess its anti-tumor efficacy through in-vitro cellular models.

Keywords: Apoptosis; Butyrate; SND1; TERC; TERT.