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Oncol Lett. 2019 Mar;17(3):3163-3172. doi: 10.3892/ol.2019.9983. Epub 2019 Jan 29.

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

Author information

1
Department of Surgery, The Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China.
2
College of Medicine, Hebei University, Baoding, Hebei 071000, P.R. China.
3
Department of Ultrasound Imaging, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong 519000, P.R. China.
4
College of Medicine, Tianjin Medical University, Tianjin 300070, P.R. China.

Abstract

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

KEYWORDS:

hepatocarcinogenesis; inflammatory cytokines; microtubule associated serine/threonine kinase-like; mitosis

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