Regulatory effect of grainyhead-like 2 gene on proliferation of epithelial ovarian cancer cells by nuclear factor erythroid-2-related factor 2 transcription

MEI Yan* ZHANG Lin YANG Hong GUAN Ping

doi:10.16098/j.issn.0529-1356.2019.04.012

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Acta Anatomica Sinica ›› 2019, Vol. 50 ›› Issue (4) : 477-482. DOI: 10.16098/j.issn.0529-1356.2019.04.012

Regulatory effect of grainyhead-like 2 gene on proliferation of epithelial ovarian cancer cells by nuclear factor erythroid-2-related factor 2 transcription

MEI Yan ^1* ZHANG Lin²YANG Hong³ GUAN Ping³

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Abstract

Objective To study the effect of nuclear factor erythroid-2-related factor 2(Nrf2) and the downstream gene grainyhead-like 2(GRHL2) on epithelial ovarian cancer cell lines and the interaction of Nrf2 and GRHL2. Methods We conducted ChIP-PCR assay to test the binding of Nrf2 with six candidate genes including GRHL2. Furthermore, we proved whether Nrf2 could bind with the GRHL2 promoter and transcriptionally activate the GRHL2 gene or not. Moreover, if the overexpression and knockdown of Nrf2 could increase and decrease the GRHL2 protein respectively. Results We discovered that fallopian tube epithelial cells taken from epithelial ovarian cancer patients and ovarian cancer cell lines highly expressed the Nrf2 and GRHL2 at mRNA level. The overexpression and knockdown of Nrf2 could increase and decrease the cells activity, respectively. However, the knockdown of GRHL2 could inhibit the influence of Nrf2 overexpression. Conclusion Nrf2 promotes the activity of epithelial ovarian cancer cells via modulating the GRHL2 gene transcriptionally.

Key words

Nuclear factor erythroid-2-related factor 2 / Grainyhead-like 2 gene / Ovarian cancer / Chromatin immunoprecipitation assay / Luciferase reporter gene assay

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MEI Yan ZHANG Lin YANG Hong GUAN Ping. Regulatory effect of grainyhead-like 2 gene on proliferation of epithelial ovarian cancer cells by nuclear factor erythroid-2-related factor 2 transcription[J]. Acta Anatomica Sinica. 2019, 50(4): 477-482 https://doi.org/10.16098/j.issn.0529-1356.2019.04.012

References

［1］ Gao M, Shih Ie M, Wang TL. The role of forkhead box Q1 transcription factor in ovarian epithelial carcinomas［J］. Int J Mol Sci,2012,13(11):13881-13893.

［2］ Oommen D, Yiannakis D, Jha AN. BRCA1 deficiency increases the sensitivity of ovarian cancer cells to auranofin［J］. Mutat Res, 2016， 784-785(11): 8-15.

［3］ Luo BH, Xiong F, Wang JP, et al. Epidermal growth factor-like domain-containing protein 7 (EGFL7) enhances EGF receptor-AKT signaling, epithelial-mesenchymal transition, and metastasis of gastric cancer cells［J］. PLoS One, 2014， 9(6): e99922.

［4］ Ibanez dCI, Battagli C, Esteller M, et al. Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients［J］. Cancer Res, 2004， 64(18): 6476-6481.

［5］ Ahmed N, Thompson EW, Quinn MA, Epithelial-mesenchymal interconversions in normal ovarian surface epithelium and ovarian carcinomas: an exception to the norm［J］. J Cell Physiol, 2007，213(3): 581-588.

［6］ Ganan Gomez Ⅰ, Wei Y, Yang H, et al. Oncogenic functions of the transcription factor Nrf2［J］. Free Radic Biol Med, 2013， 65(12): 750-764.

［7］ Tsai JJ, Dudakov JA, Takahashi K, et al. Nrf2 regulates haematopoietic stem cell function［J］. Nat Cell Biol, 2013, 15(3): 309-316.

［8］ Kumar SM， Dey A. Regulation of glutathione in health and disease with special emphasis on chronic alcoholism and hyperglycaemia mediated liver injury: a brief perspective［J］. Springer Sci Rev, 2014，2(1-2): 1-13.

［9］ Kang X, Chen W, Kim RH, et al. Regulation of the hTERT promoter activity by MSH2, the hnRNPs K and D, and GRHL2 in human oral squamous cell carcinoma cells［J］. Oncogene, 2009， 28(4): 565-574.

［10］ Xiang X, Deng Z, Zhuang X, et al. Grhl2 determines the epithelial phenotype of breast cancers and promotes tumor progression［J］. PLoS One, 2013， 8(4): 50781.

［11］ Kajiwara K, Saito A, Ogata SI, et al. Synthetic peptides corresponding to ligand-binding region of death receptors, DR5, Fas, and TNFR, specifically inhibit cell death mediated by the death ligands, respectively［J］. Biochim Biophys Acta, 2004, 1699(1-2):131-137.

［12］ Chen W, Yi JK, Shin KH, et al. Abstract 1598: grainyhead-like 2 (GRHL2) regulates the expression of forkhead box transcription factor M1 (FoxM1) in human oral cancer cells and determines tumorigenicity［J］. Cancer Res, 2014, 74(19 Suppl):1598-1598.

［13］ Xiang J, Fu X, Ran W, et al. Grhl2 reduces invasion and migration through inhibition of TGFβ-induced EMT in gastric cancer［J］. Oncogenesis, 2017, 6(1):e284.

［14］ Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway.［J］. Annu Rev Pharmacol Toxicol, 2007, 47(1):89-116.

［15］ Arif JM, Sawant SS, Sayed KAE, et al. Antiproliferative potential of sarcophine and its semisynthetic sulfur-containing derivatives against human mammary carcinoma cell lines［J］. J Natl Med, 2006, 61(2):154-158.

［16］ Chen Z, Shentu TP, Wen L, et al.Regulation of SIRT1 by oxidative stress-responsive miRNAs and a systematic approach to identify its role in the endothelium［J］. Antioxid Redox Signal, 2013, 19(13):1522-1535.

［17］ Mooney SM, Talebian Ⅴ, Jolly MK et al. The GRHL2/ZEB feedback loop-a key axis in the regulation of EMT in breast cancer［J］. J Cell Biochem, 2017, 118(9)：112-125.

［18］ Faddaoui A, Sheta R, Bachvarova M, et al.Suppression of the grainyhead transcription factor 2 gene (GRHL2) inhibits the proliferation, migration, invasion and mediates cell cycle arrest of ovarian cancer cells［J］. Cell Cycle, 2017, 16(7): 693-706.

［19］ Kensler TW, Wakabayashi N, Biswal S. Cell survival responses to environmental stresses via the Keap1-Nrf2-ARE pathway［J］. Annu Rev Pharmacol Toxicol, 2007, 47(1):89-116.

［20］ Jaiswal AK. Nrf2 signaling in coordinated activation of antioxidant gene expression ［J］. Free Radic Biol Med, 2004, 36(10):1199-1207.