TFAP4 promotes the growth of prostate cancer cells by upregulating FOXK1

Gu,Yuan; Jiang,Jiujin; Liang,Chaozhao

doi:10.3892/etm.2021.10734

TFAP4 promotes the growth of prostate cancer cells by upregulating FOXK1

Authors:
- Yuan Gu
- Jiujin Jiang
- Chaozhao Liang
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Affiliations: Department of Urology, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui 230041, P.R. China, Department of Urology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230041, P.R. China
Published online on: September 16, 2021 https://doi.org/10.3892/etm.2021.10734
Article Number: 1299
Copyright: © Gu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Transcription factor activating enhancer binding protein 4 (TFAP4) has been indicated to be correlated with the progression of various human malignancies. However, the effect and regulatory mechanism of TFAP4 in prostate cancer (PC) remain unclear. The protein and mRNA expression were detected by western blotting and RT‑qPCR. TFAP4 was overexpressed or knocked down in PC cells. The viability, invasion and migration of PC cells were analyzed by CCK‑8, Transwell and wound healing assays. The colony formation was also determined. TFAP4 expression was upregulated in PC patients and cells; high TFAP4 expression predicted poor prognosis, and was associated with a range of clinicopathological features, including metastasis, clinical stage and Gleason score. Moreover, overexpression of TFAP4 promoted cell viability, migration, and invasion in vitro, whereas knockdown of TFAP4 revealed the opposite results. TFAP4 also positively regulated forkhead box K1 (FOXK1) expression. In addition, overexpression of FOXK1 reversed the effects of TFAP4 knockdown on PC cells. These findings clarified the biologic significance of TFAP4 in PC progression and revealed an association between TFAP4 and FOXK1, thus providing a new potential target for clinical therapy of PC.

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1	Siegel RL, Fedewa SA, Miller KD, Goding-Sauer A, Pinheiro PS, Martinez-Tyson D and Jemal A: Cancer statistics for hispanics/latinos 2015. CA Cancer J Clin. 65:457–480. 2015.PubMed/NCBI View Article : Google Scholar
2	Culp MB, Soerjomataram I, Efstathiou JA, Bray F and Jemal A: Recent global patterns in prostate cancer incidence and mortality rates. Eur Urol. 77:38–52. 2020.PubMed/NCBI View Article : Google Scholar
3	Egan A, Dong Y, Zhang H, Qi Y, Balk SP and Sartor O: Castration-resistant prostate cancer: Adaptive responses in the androgen axis. Cancer Treat Rev. 40:426–433. 2014.PubMed/NCBI View Article : Google Scholar
4	Kaboré FA, Zango B, Kambou T, Ouédraogo AS, Bambara A, Yaméogo C, Kirakoya B and Lompo O: Prostate cancer disease characteristics at the time of diagnosis and initial treatment offered in a tertiary hospital at ouagadougou (Burkina Faso). Open J Urol. 4:7–12. 2014.
5	Sakar Y, Duca FA, Langelier B, Devime F, Blottiere H, Delorme C, Renault P and Covasa M: Impact of high-fat feeding on basic helix-loop-helix transcription factors controlling enteroendocrine cell differentiation. Int J Obes (Lond). 38:1482. 2014.PubMed/NCBI View Article : Google Scholar
6	Mermod N, Williams TJ and Tjian R: Enhancer binding factors AP-4 and AP-1 act in concert to activate SV40 late transcription in vitro. Nature. 332:557–561. 1988.PubMed/NCBI View Article : Google Scholar
7	Lee SU, Song HO, Lee W, Singaravelu G, Yu JR and Park WY: Identification and characterization of a putative basic helix-loop-helix (bHLH) transcription factor interacting with calcineurin in C elegans. Mol Cells. 28:455–461. 2009.PubMed/NCBI View Article : Google Scholar
8	Atchley WR and Fitch WM: A natural classification of the basic helix-loop-helix class of transcription factors. Proc Natl Acad Sci USA. 94:5172–5176. 1997.PubMed/NCBI View Article : Google Scholar
9	Wei J, Yang P, Zhang T, Chen Z, Chen W, Wanglin L, He F, Wei F, Huang D, Zhong J, et al: Overexpression of transcription factor activating enhancer binding protein 4 (TFAP4) predicts poor prognosis for colorectal cancer patients. Exp Ther Med. 14:3057–3061. 2017.PubMed/NCBI View Article : Google Scholar
10	Xinghua L, Bo Z, Yan G, Lei W, Changyao W, Qi L, Lin Y, Kaixiong T, Guobin W and Jianying C: The overexpression of AP-4 as a prognostic indicator for gastric carcinoma. Med Oncol. 29:871–877. 2012.PubMed/NCBI View Article : Google Scholar
11	Gong H, Han S, Yao H, Zhao H and Wang Y: AP-4 predicts poor prognosis in non-small cell lung cancer. Mol Med Rep. 10:336–340. 2014.PubMed/NCBI View Article : Google Scholar
12	Song J, Xie C, Jiang L, Wu G, Zhu J, Zhang S, Tang M, Song L and Li J: Transcription factor AP-4 promotes tumorigenic capability and activates the Wnt/β-catenin pathway in hepatocellular carcinoma. Theranostics. 8:3571–3583. 2018.PubMed/NCBI View Article : Google Scholar
13	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar
14	Jaeckel S, Kaller M, Jackstadt R, Götz U, Müller S, Boos S, Horst D, Jung P and Hermeking H: Ap4 is rate limiting for intestinal tumor formation by controlling the homeostasis of intestinal stem cells. Nat Commun. 9(3573)2018.PubMed/NCBI View Article : Google Scholar
15	Wu H, Liu X, Gong P, Song W, Zhou M, Li Y, Zhao Z and Fan H: Elevated TFAP4 regulates lncRNA TRERNA1 to promote cell migration and invasion in gastric cancer. Oncol Rep. 40:923–931. 2018.PubMed/NCBI View Article : Google Scholar
16	Huang T, Chen QF, Chang BY, Shen LJ, Li W, Wu PH and Fan WJ: TFAP4 promotes hepatocellular carcinoma invasion and metastasis via activating the PI3K/AKT signaling pathway. Dis Markers. 2019(7129214)2019.PubMed/NCBI View Article : Google Scholar
17	Chen C, Cai Q, He W, Lam TB, Lin J, Zhao Y, Chen X, Gu P, Huang H, Xue M, et al: AP4 modulated by the PI3K/AKT pathway promotes prostate cancer proliferation and metastasis of prostate cancer via upregulating L-plastin. Cell Death Dis. 8(e3060)2017.PubMed/NCBI View Article : Google Scholar
18	Krebs M, Solimando AG, Kalogirou C, Marquardt A, Frank T, Sokolakis I, Hatzichristodoulou G, Kneitz S, Bargou R, Kübler H, et al: miR-221-3p regulates VEGFR2 expression in high-risk prostate cancer and represents an escape mechanism from sunitinib in vitro. J Clin Mad. 9(670)2020.PubMed/NCBI View Article : Google Scholar
19	Mahn R, Heukamp LC, Rogenhofer S, Van Ruecker A, Müller SC and Ellinger JR: Circulating microRNAs (miRNA) in serum of patients with prostate cancer. Urology. 77:1265.e1269–1265.e1216. 2011.PubMed/NCBI View Article : Google Scholar
20	Xue C, Yu DM, Gherardi S, Koach J, Milazzo G, Gamble L, Liu B, Russell A, Liu T, Cheung TB, et al: Abstract 2450: MYCN and TFAP4 promote neuroblastoma malignancy by cooperating in the regulation a subset of target genes involved in cancer cell growth and metastasis. Cancer Res. 76 (Suppl 14)(S2450)2016.PubMed/NCBI View Article : Google Scholar
21	Wu M, Wang J, Tang W, Zhan X, Li Y, Peng Y, Huang X, Bai Y, Zhao J, Li A, et al: FOXK1 interaction with FHL2 promotes proliferation, invasion and metastasis in colorectal cancer. Oncogenesis. 5(e271)2016.PubMed/NCBI View Article : Google Scholar
22	Li P, Yu Z, He L, Zhou D, Xie S, Hou H and Geng X: Knockdown of FOXK1 inhibited the proliferation, migration and invasion in hepatocellular carcinoma cells. Biomed Pharmacother. 92:270–276. 2017.PubMed/NCBI View Article : Google Scholar
23	Chen D, Wang K, Li X, Jiang M, Ni L, Xu B, Chu Y, Wang W, Wang H, Kang H, et al: FOXK1 plays an oncogenic role in the development of esophageal cancer. Biochem Biophys Res Commun. 494:88–94. 2017.PubMed/NCBI View Article : Google Scholar
24	Ji ZG, Jiang HT and Zhang PS: FOXK1 promotes cell growth through activating wnt/β-catenin pathway and emerges as a novel target of miR-137 in glioma. Am J Transl Res. 10:1784–1792. 2018.PubMed/NCBI
25	Chen F, Xiong W, Dou K and Ran Q: Knockdown of FOXK1 suppresses proliferation, migration, and invasion in prostate cancer cells. Oncol Res. 25:1261–1267. 2017.PubMed/NCBI View Article : Google Scholar