Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression

Abstract

Microtubule associated serine/threonine kinase-like (MASTL) is the functional mammalian ortholog of Greatwall kinase (Gwl), which was originally discovered in <i>Drosophila</i>. Gwl is an essential kinase for accurate chromosome condensation and mitotic progression, and inhibits protein phosphatase 2A (PP2A), which subsequently dephosphorylates the substrates of cyclin B1-cyclin-dependent kinase 1, leading to mitotic exit. Previous studies have indicated that <i>MASTL</i> has a critical function in the regulation of mitosis in HeLa and U2OS cell lines, though there is currently limited evidence for the involvement of <i>MASTL</i> in hepatocarcinogenesis. The results of the present study revealed that <i>MASTL</i> was inducible by the proinflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), which promoted the proliferation and mitotic entry of human liver cancer cells. It was also determined that <i>MASTL</i> was significantly overexpressed in cancerous liver tissues compared with non-tumor liver tissues. Mechanistically, stimulation by IL-6 and TNF-α induced the trimethylation of histone H3 lysine 4 (H3K4Me3) at the <i>MASTL</i> promoter to facilitate chromatin accessibility. Additionally, H3K4Me3 was associated with the activation of nuclear factor-κB, which subsequently upregulated <i>MASTL</i> expression. These findings suggested that <i>MASTL</i> may have pivotal functions in the development of hepatocarcinoma, and that it may be a potential target for treatment.