Increased ZNF84 expression in cervical cancer

  • Peng Li
  • Hongsheng Guo
  • Guangji Zhou
  • Haiyan Shi
  • Zhen Li
  • Xiaodan Guan
  • Ziliang Deng
  • Shuxian Li
  • Shixiong Zhou
  • Yan Wang
  • Sen Wang
Gynecologic Oncology
  • 24 Downloads

Abstract

Purpose

Little is known about ZNF84 gene. This study aims to investigate ZNF84 expression in cervical cancer (CC) and the effects of ZNF84 on CC.

Materials and methods

Cervical cancer tissue specimens were collected from The First People’s Hospital of Foshan. ZNF84 and Akt expression were detected by immunohistochemistry. The influence of ZNF84 on cell proliferation was detected by CCK-8 kits. The effects of ZNF84 on Akt protein and mRNA expression were detected by western blotting and qPCR, respectively.

Results

High expression of ZNF84 protein (80.0%) was detected within CC tissues while negative expression was found in normal cervical tissues. ZNF84 was specifically associated with tumor size (p = 0.018) and negatively associated with other indicators. Further, in squamous cell carcinoma, ZNF84 was associated with both TNM staging (p = 0.041) and tumor size (p = 0.041). In vitro, we used shZNF84 to inhibit the mRNA and protein expression of ZNF84, and showed marked inhibition of cancer cell proliferation by shZNF84. Furthermore, inhibition of ZNF84 down-regulated Akt. Ly294002 (an Akt inhibitor) decreased the cell inhibition ability of shZNF84, indicating the involvement of Akt. Finally, the relationship between ZNF84 and Akt in vivo showed positive correlation (p = 0.023).

Conclusion

ZNF84 expression was increased in CC tissues and associated with tumor size. ZNF84 promoted cell proliferation which might involve Akt signal.

Keywords

ZNF84 Cervical cancer Akt Cell proliferation 

Notes

Author contributions

SW conceived and supervised the study; SW, PL, GZ and HG designed experiments; PL, HG, HS, ZL, XG, ZD and SL performed experiments; SZ and YW analyzed data; SW, PL and HG wrote the manuscript; SW made manuscript revisions.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

This study is a retrospective, non-interventional research and the Medical Ethics Committee of The First People’s Hospital of Foshan has approved the waiver of patients’ informed consent. This study has been approved by the Ethics Committee of The First People’s Hospital of Foshan, China (Number: L[2016] 3).

References

  1. 1.
    Miller J, McLachlan AD, Klug A (1985) Repetitive zinc-binding domains in the protein transcription factor IIIa from xenopus oocytes. EMBO J 4:1609–1614PubMedPubMedCentralGoogle Scholar
  2. 2.
    Frankel AD, Pabo CO (1988) Fingering too many proteins. Cell 53(5):675CrossRefPubMedGoogle Scholar
  3. 3.
    MacPherson S, Larochelle M, Turcotte B (2006) A fungal family of transcriptional regulators: the zinc cluster proteins. Microbiol Mol Biol Rev 70(3):583–604CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Smith RA, Andrews KS, Brooks D et al (2017) Cancer screening in the United States, 2017: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 67(2):100–121CrossRefPubMedGoogle Scholar
  5. 5.
    Huang RL, Chang CC, Su PH, Chen YC, Liao YP, Wang HC, Yo YT, Chao TK, Huang HC, Lin CY, Chu TY, Lai HC (2012) Methylomic analysis identifies frequent DNA methylation of zinc finger protein 582 (ZNF582) in cervical neoplasms. PLoS One 7(7):e41060CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Morandell D, Kaiser A, Herold S, Rostek U, Lechner S, Mitterberger MC, Jansen-Dürr P, Eilers M, Zwerschke W (2012) The human papillomavirus type 16 E7 oncoprotein targets Myc-interacting zinc-finger protein-1. Virology 422(2):242–253CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Wang W, Guo M, Hu L, Cai J, Zeng Y, Luo J, Shu Z, Li W, Huang Z (2012) The zinc finger protein ZNF268 is overexpressed in human cervical cancer and contributes to tumorigenesis via enhancing NF-κB signaling. J Biol Chem 287(51):42856–42866CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Brebi P, Maldonado L, Noordhuis MG et al (2014) Genome-wide methylation profiling reveals zinc finger protein 516 (ZNF516) and FK-506-binding protein 6 (FKBP6) promoters frequently methylated in cervical neoplasia, associated with HPV status and ethnicity in a Chilean population. Epigenetics 9(2):308–317CrossRefPubMedGoogle Scholar
  9. 9.
    Rosati M, Rocchi M, Storlazzi CT et al (2001) Assignment to chromosome 12q24.33, gene organization and splicing of the human KRAB/FPB containing zinc finger gene ZNF84. Cytogenet Cell Genet 94(3/4):127–130CrossRefPubMedGoogle Scholar
  10. 10.
    Assou S, Cerecedo D, Tondeur S et al (2009) A gene expression signature shared by human mature oocytes and embryonic stem cells. BMC Genom 10:10–24CrossRefGoogle Scholar
  11. 11.
    Zhang J, Cheng Y, Duan M et al (2017) Unveiling differentially expressed genes upon regulation of transcription factors in sepsis. Biotech 7(1):46–53Google Scholar
  12. 12.
    Wang S, An W, Yao Y, Chen R, Zheng X, Yang W et al (2015) Interleukin 37 expression inhibits STAT3 to suppress the proliferation and invasion of human cervical cancer cells. J Cancer 6(10):962–969CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Bahrami A, Hasanzadeh M, Hassanian SM, ShahidSales S, Ghayour-Mobarhan M, Ferns GA, Avan A (2017) The potential value of the PI3K/Akt/mTOR signaling pathway for assessing prognosis in cervical cancer and as a target for therapy. J Cell Biochem.  https://doi.org/10.1002/jcb.26118 Google Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Histology and Embryology of Basic Medical DepartmentGuangdong Medical UniversityDongguanChina
  2. 2.Pathological DepartmentThe First People’s Hospital of FoshanFoshanChina

Personalised recommendations