Zinc finger protein X-linked is overexpressed in colorectal cancer and is associated with poor prognosis

Jiang,Jin; Liu,Lu‑Ying

doi:10.3892/ol.2015.3353

Zinc finger protein X-linked is overexpressed in colorectal cancer and is associated with poor prognosis

Authors:
- Jin Jiang
- Lu‑Ying Liu
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Affiliations: Department of Medical Oncology, The First Hospital of Jiaxing, Jiaxing, Zhejiang 310012, P.R. China, Department of Radiation Oncology, Zhejiang Key Laboratory of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China
Published online on: June 10, 2015 https://doi.org/10.3892/ol.2015.3353
Pages: 810-814
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Zinc finger protein X-linked (ZFX) is a zinc finger transcription factor and plays a significant role in the self‑renewal ability of embryonic stem cells and various cancers. However, its expression and function in colorectal cancer (CRC) remain unclear. In the present study, we evaluated the expression of ZFX in CRC using quantitative polymerase chain reaction (qPCR), western blot analysis and immunohistochemistry (IHC), and further explored its potential functions in CRC cell lines using cell counting kit‑8 and Transwell invasion assays. qPCR and western blot analysis revealed that ZFX was significantly upregulated in CRC tissues; IHC further confirmed this finding, revealing that higher expression of ZFX was significantly associated with larger tumor size (P=0.01), higher pathological stage (P=0.02), depth of invasion (P=0.047), lymph node invasion (P=0.02) and higher American Joint Committee on Cancer (AJCC) stage (P=0.04). CRC patients with higher ZFX expression also exhibited significantly shorter survival times (P=0.019). Moreover, knockdown of ZFX significantly suppressed proliferation and invasion in CRC cell lines HCT116 and LoVo. These results suggest that ZFX plays a notable role in CRC tumorigenicity and may serve as a novel marker and therapeutic target for CRC.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
2	Schneider-Gädicke A, Beer-Romero P, Brown LG, Mardon G, Luoh SW and Page DC: Putative transcription activator with alternative isoforms encoded by human ZFX gene. Nature. 342:708–711. 1989. View Article : Google Scholar : PubMed/NCBI
3	Galan-Caridad JM, Harel S, Arenzana TL, Hou ZE, Doetsch FK, Mirny LA and Reizis B: Zfx controls the self-renewal of embryonic and hematopoietic stem cells. Cell. 129:345–357. 2007. View Article : Google Scholar : PubMed/NCBI
4	Cellot S and Sauvageau G: Zfx: at the crossroads of survival and self-renewal. Cell. 129:239–241. 2007. View Article : Google Scholar : PubMed/NCBI
5	Lai KP, Chen J, He M, et al: Overexpression of ZFX confers self-renewal and chemoresistance properties in hepatocellular carcinoma. Int J Cancer. 135:1790–1799. 2014. View Article : Google Scholar : PubMed/NCBI
6	Chen X, Xu H, Yuan P, Fang F, Huss M, Vega VB, Wong E, Orlov YL, Zhang W, Jiang J, et al: Integration of external signaling pathways with the core transcriptional network in embryonic stem cells. Cell. 133:1106–1117. 2008. View Article : Google Scholar : PubMed/NCBI
7	Hu G, Kim J, Xu Q, Leng Y, Orkin SH and Elledge SJ: A genome-wide RNAi screen identifies a new transcriptional module required for self-renewal. Genes Dev. 23:837–848. 2009. View Article : Google Scholar : PubMed/NCBI
8	Fang X, Huang Z, Zhou W, et al: The zinc finger transcription factor ZFX is required for maintaining the tumorigenic potential of glioblastoma stem cells. Stem Cells. 32:2033–2047. 2014. View Article : Google Scholar : PubMed/NCBI
9	Zhu Z, Li K, Xu D, Liu Y, Tang H, Xie Q, Xie L, Liu J, Wang H, Gong Y, et al: ZFX regulates glioma cell proliferation and survival in vitro and in vivo. J Neurooncol. 112:17–25. 2013. View Article : Google Scholar : PubMed/NCBI
10	Yang H, Lu Y, Zheng Y, Yu X, Xia X, He X, Feng W, Xing L and Ling Z: shRNA-mediated silencing of ZFX attenuated the proliferation of breast cancer cells. Cancer Chemother Pharmacol. 73:569–576. 2014. View Article : Google Scholar : PubMed/NCBI
11	Jiang R, Gao ZL, Sun M, Zhang XY, Wang JC and Wu H: Zinc finger X-chromosomal protein promotes growth and tumorigenesis in human osteosarcoma cells. Pak J Med Sci. 29:997–1002. 2013. View Article : Google Scholar : PubMed/NCBI
12	Jiang R, Wang JC, Sun M, Zhang XY and Wu H: Zinc finger X-chromosomal protein (ZFX) promotes solid agar colony growth of osteosarcoma cells. Oncol Res. 20:565–570. 2012. View Article : Google Scholar : PubMed/NCBI
13	Li K, Zhu ZC, Liu YJ, Liu JW, Wang HT, Xiong ZQ, Shen X, Hu ZL and Zheng J: ZFX knockdown inhibits growth and migration of non-small cell lung carcinoma cell line H1299. Int J Clin Exp Pathol. 6:2460–2467. 2013.PubMed/NCBI
14	Zha W, Cao L, Shen Y and Huang M: Roles of Mir-144-ZFX pathway in growth regulation of non-small-cell lung cancer. PLoS One. 8:e741752013. View Article : Google Scholar : PubMed/NCBI
15	Tan Z, Zhang S, Li M, Wu X, Weng H, Ding Q, Cao Y, Bao R, Shu Y, Mu J, et al: Regulation of cell proliferation and migration in gallbladder cancer by zinc finger X-chromosomal protein. Gene. 528:261–266. 2013. View Article : Google Scholar : PubMed/NCBI
16	Jiang H, Zhang L, Liu J, Chen Z, Na R, Ding G, Zhang H and Ding Q: Knockdown of zinc finger protein X-linked inhibits prostate cancer cell proliferation and induces apoptosis by activating caspase-3 and caspase-9. Cancer Gene Ther. 19:684–689. 2012. View Article : Google Scholar : PubMed/NCBI
17	Fang J, Yu Z, Lian M, Ma H, Tai J, Zhang L and Han D: Knockdown of zinc finger protein, X-linked (ZFX) inhibits cell proliferation and induces apoptosis in human laryngeal squamous cell carcinoma. Mol Cell Biochem. 360:301–307. 2012. View Article : Google Scholar : PubMed/NCBI
18	Wu S, Lao XY, Sun TT, Ren LL, Kong X, Wang JL, Wang YC, Du W, Yu YN, Weng YR, et al: Knockdown of ZFX inhibits gastric cancer cell growth in vitro and in vivo via downregulating the ERK-MAPK pathway. Cancer Lett. 337:293–300. 2013. View Article : Google Scholar : PubMed/NCBI
19	Amini S, Fathi F, Mobalegi J, Sofimajidpour H and Ghadimi T: The expressions of stem cell markers: Oct4, Nanog, Sox2, nucleostemin, Bmi, Zfx, Tcl1, Tbx3, Dppa4, and Esrrb in bladder, colon, and prostate cancer, and certain cancer cell lines. Anat Cell Biol. 47:1–11. 2014. View Article : Google Scholar : PubMed/NCBI
20	Schnabl B, Valletta D, Kirovski G and Hellerbrand C: Zinc finger protein 267 is up-regulated in hepatocellular carcinoma and promotes tumor cell proliferation and migration. Exp Mol Pathol. 91:695–701. 2011. View Article : Google Scholar : PubMed/NCBI
21	Schneider-Gädicke A, Beer-Romero P, Brown LG, Nussbaum R and Page DC: ZFX has a gene structure similar to ZFY, the putative human sex determinant, and escapes X inactivation. Cell. 57:1247–1258. 1989. View Article : Google Scholar : PubMed/NCBI
22	Li C, Ma H, Wang Y, Cao Z, Graves-Deal R, Powell AE, Starchenko A, Ayers GD, Washington MK, Kamath V, et al: Excess PLAC8 promotes an unconventional ERK2-dependent EMT in colon cancer. J Clin Invest. 124:2172–2187. 2014. View Article : Google Scholar : PubMed/NCBI
23	Kang MJ, Jung SA, Jung JM, Kim SE, Jung HK, Kim TH, Shim KN, Yi SY, Yoo K and Moon IH: Associations between single nucleotide polymorphisms of MMP2, VEGF, and HIF1A genes and the risk of developing colorectal cancer. Anticancer Res. 31:575–584. 2011.PubMed/NCBI
24	Kryczek I, Lin Y, Nagarsheth N, Peng D, Zhao L, Zhao E, Vatan L, Szeliga W, Dou Y, Owens S, et al: IL-22(+)CD4(+) T cells promote colorectal cancer stemness via STAT3 transcription factor activation and induction of the methyltransferase DOT1L. Immunity. 40:772–784. 2014. View Article : Google Scholar : PubMed/NCBI
25	Liu Z, Jiang Y, Hou Y, Hu Y, Cao X, Tao Y, Xu C, Liu S, Wang S, Wang L, et al: The IκB family member Bcl-3 stabilizes c-Myc in colorectal cancer. J Mol Cell Biol. 5:280–282. 2013. View Article : Google Scholar : PubMed/NCBI
26	Pandurangan AK: Potential targets for prevention of colorectal cancer: A focus on PI3K/Akt/mTOR and Wnt pathways. Asian Pac J Cancer Prev. 14:2201–2205. 2013. View Article : Google Scholar : PubMed/NCBI