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. 2014 Apr 21;9(4):e95043.
doi: 10.1371/journal.pone.0095043. eCollection 2014.

Gankyrin is frequently overexpressed in cervical high grade disease and is associated with cervical carcinogenesis and metastasis

Yuan Liu  1 , Jiawen Zhang  2 , Wenyan Qian  3 , Yu Dong  1 , Yongbin Yang  1 , Zhiqiang Liu  4 , Youji Feng  1 , Ding Ma  5 , Zhenbo Zhang  1 , Sufang Wu  1
Affiliations

Gankyrin is frequently overexpressed in cervical high grade disease and is associated with cervical carcinogenesis and metastasis

Yuan Liu et al. PLoS One. .

Abstract

Our previous studies have showed that Gankyrin expression is correlated with a malignant phenotype in endometrial carcinoma. Here, we investigated the possible role of Gankyrin in cervical disease. The increasing protein level of Gankyrin was observed in high-grade cervical intraepithelial neoplasia and carcinoma compared with benign cervical tissues and low-grade cervical intraepithelial neoplasia. In para-carcinoma tissues, it was found interestingly that there was no lymph node metastasis when nuclei Gankyrin was positively expressed, but lymph node metastasis rate was 30% (6/20) when nuclei Gankyrin was negatively expressed. In vitro, the transfection of Gankyrin resulted in markedly up-regulating of Vimentin, β-catenin and Twist2, as well as down-regulating of E-cadherin in cervical carcinoma cells. Our results suggested that Gankyrin may be functional in cervical carcinogenesis and metastasis.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. The expression of Gankyrin in all grades of cervical disease by immunohistochemistry staining assay (×200).
A. The expression of Gankyrin in normal cervical squamous epithelial; B. The expression of Gankyrin in CIN I; C. The expression of Gankyrin in CIN II–III; D. The expression of Gankyrin in SCC.
Figure 2
Figure 2. The expression of Gankyrin in 30 pairs of cervical tumor and tumor adjacent tissues by immunohistochemistry staining assay (×200):
A. The expression of Gankyrin in cervical carcinoma tissues. B. The expression of Gankyrin in carcinoma adjacent tissues.
Figure 3
Figure 3. The effects of pMKITneo-hGankyrin plasmid or siGankyrin transfections on cervical carcinoma cells prolifection.
The histograms represent cell proliferation at 72h after transfection with pMKITneo-hGankyrin plasmid and siRNA of Gankyrin, respectively. The proliferation of SiHa and HeLa cells transfected with pMKITneo-hGankyrin plasmid was significantly higher than the control groups (*p<0.05). Gankyrin siRNA inhibited proliferation of SiHa and HeLa cells, as compared to the control groups (*p<0.05).
Figure 4
Figure 4. The expression of the hallmarks of EMT (E-cadherin, Vimentin), β-catenin, Twist2 and cyclinD1 after SiHa and HeLa cells were transfected with Gankyrin plasmid or siRNA of Gankyrin.
The transfection of Gankyrin could lead to the up-regualtion of β-catenin, Twist2, cyclinD1 and Vimentin, as well as the down-regulation of E-cadherin. While the knock-down of Gankyrin had an opposite effect on SiHa and HeLa cells line.
Figure 5
Figure 5. Effect of Gankyrin on invasion of SiHa and HeLa cells line.
Microphotographs show representative fields of Giemsa-stained lower membranes of the Boyden chambers; histograms show number of pMKITneo-hGankyrin plasmid and siRNA of Gankyrin treated cells counted by trypan blue exclusion (expressed as % of untreated cells taken as 100). *p<0.05, compared with SiHa-blank group.
See this image and copyright information in PMC

References

    1. Siegel R, Naishadham D, Jemal A (2012) Cancer statistics, 2012. CA Cancer J Clin 62: 10–29. - PubMed
    1. Woodman CB, Collins SI, Young LS (2007) The natural history of cervical HPV infection: unresolved issues. Nat Rev Cancer 7: 11–22. - PubMed
    1. zur Hausen H (2002) Papillomaviruses and cancer: from basic studies to clinical application. Nat Rev Cancer 2: 342–350. - PubMed
    1. Zhang J, Yang Y, Zhang Z, He Y, Liu Z, et al. (2013) Gankyrin plays an essential role in estrogen-driven and GPR30-mediated endometrial carcinoma cell proliferation via the PTEN/PI3K/AKT signaling pathway. Cancer Lett 339: 279–287. - PubMed
    1. Fu XY, Wang HY, Tan L, Liu SQ, Cao HF, et al. (2002) Overexpression of p28/gankyrin in human hepatocellular carcinoma and its clinical significance. World J Gastroenterol 8: 638–643. - PMC - PubMed

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