ZNF217: An Oncogenic Transcription Factor and Potential Therapeutic Target for Multiple Human Cancers

Figures & data

Figure 1 ZNF 217 plays a role in cancer and other diseases through specific pathways with different expression levels. Created with BioRender.com.

Figure 2 Interactions between ZNF217 and other genes.

Figure 3 Post-translational modifications of ZNF217. (This figure is cited from the PhosphoSite Plus database).

Table 1 Regulatory Effect of ZNF217 Expression on Cancer Progression

Tumor or Cell	Changes of ZNF217	Key Result	References
Human breast tumor	Upregulated	ZNF217 stimulates metastatic bone growth in breast cancer by modulating the bone morphogenetic protein (BMP) signaling pathway.	[14,15]
Immortalized ovarian surface epithelial cell	Upregulated	ZNF217 acts early in ovarian tumor progression through upregulation of EEF1A2 to promote tumor cell immortalization.	[17]
Hepatocellular carcinoma	Upregulated	ZNF217 inhibits the expression of CDH1 by recruiting LSD1, thereby affecting the synthesis of E-cadherin and promoting tumor EMT.	[30]
Osteosarcoma	Upregulated	ZNF217 promotes osteosarcoma development and in situ growth and metastasis through the regulation of an oncogene network regulated by activation of the PI3K-AKT signaling pathway.	[37]
Human breast tumor	Upregulated	ZNF217 drives overexpression of erbB3 and leads to activation of AKT and MAPK pathways, thereby promoting tumor growth and chemoresistance.	[57,58]
Human mammary epithelial cell	Upregulated	ZNF217 inhibits tumor cell apoptosis by promoting overexpression of telomerase TRF2 and maintaining telomere stability.	[63]
Human breast tumor	Upregulated	ZNF217 accelerates the proliferation of tumor cells by negatively regulating the expression of P15 (ink4b) tumor suppressor.	[65,66]

Figure 4 LncRNA inhibits the negative regulation of ZNF217 by miRNA either by acting as a miRNA sponge or directly promoting ZNF217 expression. This enhances ZNF217 expression, thereby promoting disease progression, such as in tumors. Created with BioRender.com.

Figure 5 miRNAs negatively regulate ZNF217 expression by targeting ZNF217, thereby inhibiting cancer development and EMT. Created with BioRender.com.

Figure 6 Circular RNA functions as a sponge for miRNA to counteract its inhibitory effect on ZNF217, leading to increased expression of ZNF217 and ultimately promoting the progression of tumors and other diseases. Created with BioRender.com.

Bellanger A, Donini CF, Vendrell JA, et al. The critical role of the ZNF217 oncogene in promoting breast cancer metastasis to the bone. J Pathol. 2017;242(1):73–89. doi:10.1002/path.4882

 PubMed Web of Science ®Google Scholar

Vollaire J, Machuca-Gayet I, Lavaud J, et al. The bone morphogenetic protein signaling inhibitor LDN-193189 enhances metastasis development in mice. Front Pharmacol. 2019;10:667. doi:10.3389/fphar.2019.00667

 PubMed Web of Science ®Google Scholar

Sun Y, Wong N, Guan Y, et al. The eukaryotic translation elongation factor eEF1A2 induces neoplastic properties and mediates tumorigenic effects of ZNF217 in precursor cells of human ovarian carcinomas. Int, J, Cancer. 2008;123(8):1761–1769. doi:10.1002/ijc.23708

 PubMed Web of Science ®Google Scholar

Si W, Zhao Y, Zhou J, Zhang Q, Zhang Y. The coordination between ZNF217 and LSD1 contributes to hepatocellular carcinoma progress and is negatively regulated by miR-101. Exp Cell Res. 2019;379(1):1–10. doi:10.1016/j.yexcr.2019.03.017

 PubMed Web of Science ®Google Scholar

Smeester BA, Draper GM, Slipek NJ, et al. Implication of ZNF217 in accelerating tumor development and therapeutically targeting ZNF217-Induced PI3K-AKT signaling for the treatment of metastatic osteosarcoma. Mol Cancer Ther. 2020;19(12):2528–2541. doi:10.1158/1535-7163.MCT-20-0369

 PubMed Web of Science ®Google Scholar

Krig SR, Miller JK, Frietze S, et al. ZNF217, a candidate breast cancer oncogene amplified at 20q13, regulates expression of the ErbB3 receptor tyrosine kinase in breast cancer cells. Oncogene. 2010;29(40):5500–5510. doi:10.1038/onc.2010.289

 PubMed Web of Science ®Google Scholar

Littlepage LE, Adler AS, Kouros-Mehr H, et al. The transcription factor ZNF217 is a prognostic biomarker and therapeutic target during breast cancer progression. Cancer Discov. 2012;2(7):638–651. doi:10.1158/2159-8290.CD-12-0093

 PubMed Web of Science ®Google Scholar

Nijjar T, Bassett E, Garbe J, et al. Accumulation and altered localization of telomere-associated protein TRF2 in immortally transformed and tumor-derived human breast cells. Oncogene. 2005;24(20):3369–3376. doi:10.1038/sj.onc.1208482

 PubMed Web of Science ®Google Scholar

Thillainadesan G, Isovic M, Loney E, Andrews J, Tini M, Torchia J. Genome analysis identifies the p15ink4b tumor suppressor as a direct target of the ZNF217/CoREST complex. Mol Cell Biol. 2008;28(19):6066–6077. doi:10.1128/MCB.00246-08

 PubMed Web of Science ®Google Scholar

Thillainadesan G, Chitilian JM, Isovic M, et al. TGF-β-dependent active demethylation and expression of the p15ink4b tumor suppressor are impaired by the ZNF217/CoREST complex. Mol Cell. 2012;46(5):636–649. doi:10.1016/j.molcel.2012.03.027

 PubMed Web of Science ®Google Scholar