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

  • Authors:
    • Liye Cao
    • Wen‑Juan Li
    • Ji‑Hong Yang
    • Yu Wang
    • Zhi‑Juan Hua
    • Dan Liu
    • Ya‑Qing Chen
    • Hao‑Miao Zhang
    • Rui Zhang
    • Ji‑Sen Zhao
    • Shu‑Jie Cheng
    • Quan Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Surgery, The Affiliated Hospital of Hebei University, Baoding, Hebei 071000, P.R. China, College of Medicine, Hebei University, Baoding, Hebei 071000, P.R. China, Department of Ultrasound Imaging, Zhuhai People's Hospital (Zhuhai Hospital Affiliated with Jinan University), Zhuhai, Guangdong 519000, P.R. China, College of Medicine, Tianjin Medical University, Tianjin 300070, P.R. China
    Copyright: © Cao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 3163-3172
    |
    Published online on: January 29, 2019
       https://doi.org/10.3892/ol.2019.9983
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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.
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1 

Nasmyth K: Viewpoint: Putting the cell cycle in order. Science. 274:1643–1645. 1996. View Article : Google Scholar : PubMed/NCBI

2 

Murray AW: Recycling the cell cycle: Cyclins revisited. Cell. 116:221–234. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Davydenko O, Schultz RM and Lampson MA: Increased CDK1 activity determines the timing of kinetochore-microtubule attachments in meiosis I. J Cell Biol. 202:221–229. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Chang HY, Jennings PC, Stewart J, Verrills NM and Jones KT: Essential role of protein phosphatase 2A in metaphase II arrest and activation of mouse eggs shown by okadaic acid, dominant negative protein phosphatase 2A, and FTY720. J Biol Chem. 286:14705–14712. 2011. View Article : Google Scholar : PubMed/NCBI

5 

Yu J, Fleming SL, Williams B, Williams EV, Li Z, Somma P, Rieder CL and Goldberg ML: Greatwall kinase: A nuclear protein required for proper chromosome condensation and mitotic progression in Drosophila. J Cell Biol. 164:487–492. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Wang P, Malumbres M and Archambault V: The Greatwall-PP2A axis in cell cycle control. Methods Mol Biol. 1170:99–111. 2014. View Article : Google Scholar : PubMed/NCBI

7 

Cundell MJ, Bastos RN, Zhang T, Holder J, Gruneberg U, Novak B and Barr FA: The BEG (PP2A-B55/ENSA/Greatwall) pathway ensures cytokinesis follows chromosome separation. Mol Cell. 52:393–405. 2013. View Article : Google Scholar : PubMed/NCBI

8 

Voets E and Wolthuis RM: MASTL is the human orthologue of Greatwall kinase that facilitates mitotic entry, anaphase and cytokinesis. Cell Cycle. 9:3591–3601. 2010. View Article : Google Scholar : PubMed/NCBI

9 

Nagel R, Stigter-van Walsum M, Buijze M, van den Berg J, van der Meulen IH, Hodzic J, Piersma SR, Pham TV, Jiménez CR, van Beusechem VW and Brakenhoff RH: Genome-wide siRNA screen identifies the radiosensitizing effect of downregulation of MASTL and FOXM1 in NSCLC. Mol Cancer Ther. 14:1434–1444. 2015. View Article : Google Scholar : PubMed/NCBI

10 

Johnson HJ, Gandhi MJ, Shafizadeh E, Langer NB, Pierce EL, Paw BH, Gilligan DM and Drachman JG: In vivo inactivation of MASTL kinase results in thrombocytopenia. Exp Hematol. 37:901–908. 2009. View Article : Google Scholar : PubMed/NCBI

11 

El-Serag HB and Rudolph KL: Hepatocellular carcinoma: Epidemiology and molecular carcinogenesis. Gastroenterology. 132:2557–2576. 2007. View Article : Google Scholar : PubMed/NCBI

12 

Grivennikov SI, Greten FR and Karin M: Immunity, inflammation, and cancer. Cell. 140:883–899. 2010. View Article : Google Scholar : PubMed/NCBI

13 

Hoshida Y, Toffanin S, Lachenmayer A, Villanueva A, Minguez B and Llovet JM: Molecular classification and novel targets in hepatocellular carcinoma: Recent advancements. Semin Liver Dis. 30:35–51. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Hartwell LH and Kastan MB: Cell cycle control and cancer. Science. 266:1821–1828. 1994. View Article : Google Scholar : PubMed/NCBI

15 

Chaturvedi P, Eng WK, Zhu Y, Mattern MR, Mishra R, Hurle MR, Zhang X, Annan RS, Lu Q, Faucette LF, et al: Mammalian Chk2 is a downstream effector of the ATM-dependent DNA damage checkpoint pathway. Oncogene. 18:4047–4054. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Zeng JZ, Wang HY, Chen ZJ, Ullrich A and Wu MC: Molecular cloning and characterization of a novel gene which is highly expressed in hepatocellular carcinoma. Oncogene. 21:4932–4943. 2002. View Article : Google Scholar : PubMed/NCBI

17 

Bishayee A: The role of inflammation and liver cancer. Adv Exp Med Biol. 816:401–435. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Hodge DR, Hurt EM and Farrar WL: The role of IL-6 and STAT3 in inflammation and cancer. Eur J Cancer. 41:2502–2512. 2005. View Article : Google Scholar : PubMed/NCBI

19 

Pfaffi MW: A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 29:e452001. View Article : Google Scholar : PubMed/NCBI

20 

El-Serag HB: Hepatocellular carcinoma. N Engl J Med. 365:1118–1127. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Naugler WE, Sakurai T, Kim S, Maeda S, Kim K, Elsharkawy AM and Karin M: Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production. Science. 317:121–124. 2007. View Article : Google Scholar : PubMed/NCBI

22 

Park EJ, Lee JH, Yu GY, He G, Ali SR, Holzer RG, Osterreicher CH, Takahashi H and Karin M: Dietary and genetic obesity promote liver inflammation and tumorigenesis by enhancing IL-6 and TNF expression. Cell. 140:197–208. 2010. View Article : Google Scholar : PubMed/NCBI

23 

He G, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, Seki E, Yost SE, Jepsen K, et al: Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell. 155:384–396. 2013. View Article : Google Scholar : PubMed/NCBI

24 

Iliopoulos D, Hirsch HA and Struhl K: An epigenetic switch involving NF-kappaB, Lin28, Let-7 MicroRNA, and IL6 links inflammation to cell transformation. Cell. 139:693–706. 2009. View Article : Google Scholar : PubMed/NCBI

25 

Pilati C, Amessou M, Bihl MP, Balabaud C, Nhieu JT, Paradis V, Nault JC, Izard T, Bioulac-Sage P, Couchy G, et al: Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas. J Exp Med. 208:1359–1366. 2011. View Article : Google Scholar : PubMed/NCBI

26 

Mochida S, Maslen SL, Skehel M and Hunt T: Greatwall phosphorylates an inhibitor of protein phosphatase 2A that is essential for mitosis. Science. 330:1670–1673. 2010. View Article : Google Scholar : PubMed/NCBI

27 

Gharbi-Ayachi A, Labbé JC, Burgess A, Vigneron S, Strub JM, Brioudes E, Van-Dorsselaer A, Castro A and Lorca T: The substrate of Greatwall kinase, Arpp19, controls mitosis by inhibiting protein phosphatase 2A. Science. 330:1673–1677. 2010. View Article : Google Scholar : PubMed/NCBI

28 

Burgess A, Vigneron S, Brioudes E, Labbé JC, Lorca T and Castro A: Loss of human Greatwall results in G2 arrest and multiple mitotic defects due to deregulation of the cyclin B-Cdc2/PP2A balance. Proc Natl Acad Sci USA. 107:12564–12569. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Ghosh S and Karin M: Missing pieces in the NF-kappaB puzzle. Cell 109 (Suppl). S81–S96. 2002.

30 

Xing S, Zhang B, Hua R, Tai WC, Zeng Z, Xie B, Huang C, Xue J, Xiong S, Yang J, et al: URG4/URGCP enhances the angiogenic capacity of human hepatocellular carcinoma cells in vitro via activation of the NF-κB signaling pathway. BMC Cancer. 15:3682015. View Article : Google Scholar : PubMed/NCBI

31 

Wang Y, Tu Q, Yan W, Xiao D, Zeng Z, Ouyang Y, Huang L, Cai J, Zeng X, Chen YJ and Liu A: CXC195 suppresses proliferation and inflammatory response in LPS-induced human hepatocellular carcinoma cells via regulating TLR4-MyD88-TAK1-mediated NF-κB and MAPK pathway. Biochem Biophys Res Commun. 456:373–379. 2015. View Article : Google Scholar : PubMed/NCBI

32 

Lu X, Ma P, Shi Y, Yao M, Hou L, Zhang P and Jiang L: NF-κB increased expression of 17β-hydroxysteroid dehydrogenase 4 promotes HepG2 proliferation via inactivating estradiol. Mol Cell Endocrinol. 401:1–11. 2015. View Article : Google Scholar : PubMed/NCBI

33 

He G and Karin M: NF-κB and STAT3-key players in liver inflammation and cancer. Cell Res. 21:159–168. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Yu J, Zhao Y, Li Z, Galas S and Goldberg ML: Greatwall kinase participates in the Cdc2 autoregulatory loop in Xenopus egg extracts. Mol Cell. 22:83–91. 2006. View Article : Google Scholar : PubMed/NCBI

35 

Qian Y and Chen X: Tumor suppression by p53: Making cells senescent. Histol Histopathol. 25:515–526. 2010.PubMed/NCBI

36 

Hanahan D and Weinberg RA: The hallmarks of cancer. Cell. 100:57–70. 2000. View Article : Google Scholar : PubMed/NCBI

37 

Hermeking H: MicroRNAs in the p53 network: Micromanagement of tumour suppression. Nat Rev Cancer. 12:613–626. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Lorca T and Castro A: The Greatwall kinase: A new pathway in the control of the cell cycle. Oncogene. 32:537–543. 2013. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Cao L, Li WJ, Yang JH, Wang Y, Hua ZJ, Liu D, Chen YQ, Zhang HM, Zhang R, Zhao JS, Zhao JS, et al: Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression. Oncol Lett 17: 3163-3172, 2019.
APA
Cao, L., Li, W., Yang, J., Wang, Y., Hua, Z., Liu, D. ... Zhang, Q. (2019). Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression. Oncology Letters, 17, 3163-3172. https://doi.org/10.3892/ol.2019.9983
MLA
Cao, L., Li, W., Yang, J., Wang, Y., Hua, Z., Liu, D., Chen, Y., Zhang, H., Zhang, R., Zhao, J., Cheng, S., Zhang, Q."Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression". Oncology Letters 17.3 (2019): 3163-3172.
Chicago
Cao, L., Li, W., Yang, J., Wang, Y., Hua, Z., Liu, D., Chen, Y., Zhang, H., Zhang, R., Zhao, J., Cheng, S., Zhang, Q."Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression". Oncology Letters 17, no. 3 (2019): 3163-3172. https://doi.org/10.3892/ol.2019.9983
Copy and paste a formatted citation
x
Spandidos Publications style
Cao L, Li WJ, Yang JH, Wang Y, Hua ZJ, Liu D, Chen YQ, Zhang HM, Zhang R, Zhao JS, Zhao JS, et al: Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression. Oncol Lett 17: 3163-3172, 2019.
APA
Cao, L., Li, W., Yang, J., Wang, Y., Hua, Z., Liu, D. ... Zhang, Q. (2019). Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression. Oncology Letters, 17, 3163-3172. https://doi.org/10.3892/ol.2019.9983
MLA
Cao, L., Li, W., Yang, J., Wang, Y., Hua, Z., Liu, D., Chen, Y., Zhang, H., Zhang, R., Zhao, J., Cheng, S., Zhang, Q."Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression". Oncology Letters 17.3 (2019): 3163-3172.
Chicago
Cao, L., Li, W., Yang, J., Wang, Y., Hua, Z., Liu, D., Chen, Y., Zhang, H., Zhang, R., Zhao, J., Cheng, S., Zhang, Q."Inflammatory cytokine‑induced expression of MASTL is involved in hepatocarcinogenesis by regulating cell cycle progression". Oncology Letters 17, no. 3 (2019): 3163-3172. https://doi.org/10.3892/ol.2019.9983
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