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

Microtubule associated serine/threonine kinase-like (MASTL) is the functional mammalian ortholog of Greatwall kinase (Gwl), which was originally discovered in . 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 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 in hepatocarcinogenesis. The results of the present study revealed that 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 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 promoter to facilitate chromatin accessibility. Additionally, H3K4Me3 was associated with the activation of nuclear factor-κB, which subsequently upregulated expression. These findings suggested that may have pivotal functions in the development of hepatocarcinoma, and that it may be a potential target for treatment.