Mitogen-activated protein kinase kinase 3 induces cell cycle arrest via p38 activation mediated Bmi-1 downregulation in hepatocellular carcinoma

  • Authors:
    • Lin Wang
    • Chen Chen
    • Shuzhi Feng
    • Ping Lei
    • Jianli Tian
  • View Affiliations

  • Published online on: November 13, 2015     https://doi.org/10.3892/mmr.2015.4564
  • Pages: 243-248
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

The underlying molecular pathogenesis of hepatocellular carcinoma (HCC) remains poorly understood. Mitogen-activated protein kinase kinase 3 (MKK3), has been reported as a novel tumor suppressor in breast cancer. However, its potential suppressive role in HCC has not been evaluated. In the current study, the biologic functions of MKK3 in HCC were investigated and a previously unreported cell cycle regulation mechanism was observed. MKK3 overexpression suppressed HepG2 and PLC‑PRF‑5 cell proliferation and induced cell cycle arrest in the two cell lines. In addition, MKK3 overexpression upregulated the cyclin-dependent kinase inhibitors, p16 INK4A and p15 INK4B in HCC cells. Their negative regulator, Bim‑1, was downregulated following MKK3 overexpression. Moreover, MKK3 activated p38 in HCC cells and SB203580, a p38 inhibitor, reversed the tumor suppressive effect of MKK3. In conclusion, the results identify MKK3 as a tumor suppressor and highlighted the significance of p38 pathway aberration in HCC.
View Figures
View References

Related Articles

Journal Cover

January-2016
Volume 13 Issue 1

Print ISSN: 1791-2997
Online ISSN:1791-3004

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Wang L, Chen C, Feng S, Lei P and Tian J: Mitogen-activated protein kinase kinase 3 induces cell cycle arrest via p38 activation mediated Bmi-1 downregulation in hepatocellular carcinoma. Mol Med Rep 13: 243-248, 2016.
APA
Wang, L., Chen, C., Feng, S., Lei, P., & Tian, J. (2016). Mitogen-activated protein kinase kinase 3 induces cell cycle arrest via p38 activation mediated Bmi-1 downregulation in hepatocellular carcinoma. Molecular Medicine Reports, 13, 243-248. https://doi.org/10.3892/mmr.2015.4564
MLA
Wang, L., Chen, C., Feng, S., Lei, P., Tian, J."Mitogen-activated protein kinase kinase 3 induces cell cycle arrest via p38 activation mediated Bmi-1 downregulation in hepatocellular carcinoma". Molecular Medicine Reports 13.1 (2016): 243-248.
Chicago
Wang, L., Chen, C., Feng, S., Lei, P., Tian, J."Mitogen-activated protein kinase kinase 3 induces cell cycle arrest via p38 activation mediated Bmi-1 downregulation in hepatocellular carcinoma". Molecular Medicine Reports 13, no. 1 (2016): 243-248. https://doi.org/10.3892/mmr.2015.4564