Nuclear factor I/B mediates epithelial‑mesenchymal transition in human melanoma cells through ZEB1

Cheng,Ruimin; Gao,Sheng; Hu,Wei; Liu,Yamei; Cao,Yuchun

doi:10.3892/ol.2020.12342

Nuclear factor I/B mediates epithelial‑mesenchymal transition in human melanoma cells through ZEB1

Authors:
- Ruimin Cheng
- Sheng Gao
- Wei Hu
- Yamei Liu
- Yuchun Cao
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Affiliations: Department of Dermatology, Tongji Hospital, The Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P.R. China
Published online on: December 1, 2020 https://doi.org/10.3892/ol.2020.12342
Article Number: 81
Copyright: © Cheng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The relationship between nuclear factor I/B (NFIB) and cancer attracts growing research interest. NFIB has diverse and specific roles in tumor progression and invasion. However, the potential effects and functions of this transcription factor in melanoma remain unclear. The present study sought to determine the distinguishing properties of NFIB in melanoma cells. Immunohistochemical examination of the tissues of 15 patients with melanoma indicated that the expression of NFIB was high in melanoma specimens, compared with the benign nevus and normal skin specimens. In addition, the relationship between high NFIB expression and low overall survival rate was assessed. Functional studies demonstrated that NFIB enhanced the malignancy of melanoma, including proliferation, migration and invasion. In addition, NFIB silencing in A375 and A875 cell lines inhibited the process of epithelial‑mesenchymal transition (EMT), upregulated E‑cadherin and zona occludens‑1, but suppressed N‑cadherin and vimentin expression. These findings may suggest a new function of NFIB in promoting the migration and invasion of melanoma cells. Therefore, the present study further evaluated the association between NFIB and zinc finger protein E‑box binding homeobox‑1 (ZEB1) in melanoma. Mechanistic experiments revealed that NFIB exerted its roles during EMT by regulating ZEB1. Overall, the present data indicates that NFIB promotes the malignancy of melanoma, particularly EMT, by modulating the ZEB1 axis, such as ZEB2, ATM and CHK1, which may represent a potential molecular therapeutic target in melanoma.

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1	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2012. CA Cancer J Clin. 62:10–29. 2012. View Article : Google Scholar
2	Siegel R, DeSantis C, Virgo K, Stein K, Mariotto A, Smith T, Cooper D, Gansler T, Lerro C, Fedewa S, et al: Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 62:220–241. 2012. View Article : Google Scholar
3	Boyle GM: Therapy for metastatic melanoma: An overview and update. Expert Rev Anticancer Ther. 11:725–737. 2011. View Article : Google Scholar
4	Siegel R, Ma J, Zou Z and Jemal A: Cancer statistics, 2014. CA Cancer J Clin. 64:9–29. 2014. View Article : Google Scholar
5	Miller AJ and Mihm MC Jr: Melanoma. N Engl J Med. 355:51–65. 2006. View Article : Google Scholar
6	Mirzaei H, Gholamin S, Shahidsales S, Sahebkar A, Jaafari MR, Mirzaei HR, Hassanian SM and Avan A: MicroRNAs as potential diagnostic and prognostic biomarkers in melanoma. Eur J Cancer. 53:25–32. 2016. View Article : Google Scholar
7	Eggermont AM and Kirkwood JM: Re-evaluating the role of dacarbazine in metastatic melanoma: What have we learned in 30 years? Eur J Cancer. 40:1825–1836. 2004. View Article : Google Scholar
8	Kalluri R and Weinberg RA: The basics of epithelial-mesenchymal transition. J Clin Invest. 119:1420–1428. 2009. View Article : Google Scholar
9	Pastushenko I and Blanpain C: EMT transition states during tumor progression and metastasis. Trends Cell Biol. 29:212–226. 2019. View Article : Google Scholar
10	Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell. 144:646–674. 2011. View Article : Google Scholar
11	Caramel J, Papadogeorgakis E, Hill L, Browne GJ, Richard G, Wierinckx A, Saldanha G, Osborne J, Hutchinson P, Tse G, et al: A switch in the expression of embryonic EMT-inducers drives the development of malignant melanoma. Cancer Cell. 24:466–480. 2013. View Article : Google Scholar
12	Denecker G, Vandamme N, Akay O, Koludrovic D, Taminau J, Lemeire K, Gheldof A, De Craene B, Van Gele M, Brochez L, et al: Identification of a ZEB2-MITF-ZEB1 transcriptional network that controls melanogenesis and melanoma progression. Cell Death Differ. 21:1250–1261. 2014. View Article : Google Scholar
13	Blomquist P, Belikov S and Wrange O: Increased nuclear factor 1 binding to its nucleosomal site mediated by sequence-dependent DNA structure. Nucleic Acids Res. 27:517–525. 1999. View Article : Google Scholar
14	Gronostajski RM: Roles of the NFI/CTF gene family in transcription and development. Gene. 249:31–45. 2000. View Article : Google Scholar
15	Chaudhry AZ, Lyons GE and Gronostajski RM: Expression patterns of the four nuclear factor I genes during mouse embryogenesis indicate a potential role in development. Dev Dyn. 208:313–325. 1997. View Article : Google Scholar
16	Li S and Rosen JM: Nuclear factor I and mammary gland factor (STAT5) play a critical role in regulating rat whey acidic protein gene expression in transgenic mice. Mol Cell Biol. 15:2063–2070. 1995. View Article : Google Scholar
17	Kane R, Finlay D, Lamb T and Martin F: Transcription factor NF 1 expression in involuting mammary gland. Adv Exp Med Biol. 480:117–122. 2000. View Article : Google Scholar
18	Chen KS, Lim JWC, Richards LJ and Bunt J: The convergent roles of the nuclear factor I transcription factors in development and cancer. Cancer Lett. 410:124–138. 2017. View Article : Google Scholar
19	Stringer BW, Bunt J, Day BW, Barry G, Jamieson PR, Ensbey KS, Bruce ZC, Goasdoué K, Vidal H, Charmsaz S, et al: Nuclear factor one B (NFIB) encodes a subtype-specific tumour suppressor in glioblastoma. Oncotarget. 7:29306–29320. 2016. View Article : Google Scholar
20	Moon HG, Hwang KT, Kim JA, Kim HS, Lee MJ, Jung EM, Ko E, Han W and Noh DY: NFIB is a potential target for estrogen receptor-negative breast cancers. Mol Oncol. 5:538–544. 2011. View Article : Google Scholar
21	Xing D, Bakhsh S, Melnyk N, Isacson C, Ho J, Huntsman DG, Gilks CB, Ronnett BM and Horlings HM: Frequent NFIB-associated gene rearrangement in adenoid cystic carcinoma of the vulva. Int J Gynecol Pathol. 36:289–293. 2017. View Article : Google Scholar
22	Liu Z, Chen J, Yuan W, Ruan H, Shu Y, Ji J, Wu L, Tang Q, Zhou Z, Zhang X, et al: Nuclear factor I/B promotes colorectal cancer cell proliferation, epithelial-mesenchymal transition and 5-fluorouracil resistance. Cancer Sci. 110:86–98. 2019. View Article : Google Scholar
23	Fane ME, Chhabra Y, Hollingsworth DEJ, Simmons JL, Spoerri L, Oh TG, Chauhan J, Chin T, Harris L, Harvey TJ, et al: NFIB Mediates BRN2 driven melanoma cell migration and invasion through regulation of EZH2 and MITF. Ebiomedicine. 16:63–75. 2017. View Article : Google Scholar
24	Hebert SL, Simmons C, Thompson AL, Zorc CS, Blalock EM and Kraner SD: Basic helix-loop-helix factors recruit nuclear factor I to enhance expression of the NaV 1.4 Na⁺ channel gene. Biochim Biophys Acta. 1769:649–658. 2007. View Article : Google Scholar
25	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. View Article : Google Scholar
26	Chaffer CL, San Juan BP, Lim E and Weinberg RA: EMT, cell plasticity and metastasis. Cancer Metastasis Rev. 35:645–654. 2016. View Article : Google Scholar
27	Barry G, Piper M, Lindwall C, Moldrich R, Mason S, Little E, Sarkar A, Tole S, Gronostajski RM and Richards LJ: Specific glial populations regulate hippocampal morphogenesis. J Neurosci. 28:12328–12340. 2008. View Article : Google Scholar
28	Piper M, Barry G, Harvey TJ, McLeay R, Smith AG, Harris L, Mason S, Stringer BW, Day BW, Wray NR, et al: NFIB-mediated repression of the epigenetic factor Ezh2 regulates cortical development. J Neurosci. 34:2921–2930. 2014. View Article : Google Scholar
29	Becker-Santos DD, Lonergan KM, Gronostajski RM and Lam WL: Nuclear factor I/B: A master regulator of cell differentiation with paradoxical roles in cancer. EBioMedicine. 22:2–9. 2017. View Article : Google Scholar
30	Suzuki H, Aoki K, Chiba K, Sato Y, Shiozawa Y, Shiraishi Y, Shimamura T, Niida A, Motomura K, Ohka F, et al: Mutational landscape and clonal architecture in grade II and III gliomas. Nat Genet. 47:458–468. 2015. View Article : Google Scholar
31	Dooley AL, Winslow MM, Chiang DY, Banerji S, Stransky N, Dayton TL, Snyder EL, Senna S, Whittaker CA, Bronson RT, et al: Nuclear factor I/B is an oncogene in small cell lung cancer. Genes Dev. 25:1470–1475. 2011. View Article : Google Scholar
32	Brayer KJ, Frerich CA, Kang H and Ness SA: Recurrent fusions in MYB and MYBL1 define a common, transcription factor-driven oncogenic pathway in salivary gland adenoid cystic carcinoma. Cancer Discov. 6:176–187. 2016. View Article : Google Scholar
33	Denny SK, Yang D, Chuang CH, Brady JJ, Lim JS, Grüner BM, Chiou SH, Schep AN, Baral J, Hamard C, et al: Nfib promotes metastasis through a widespread increase in chromatin accessibility. Cell. 166:328–342. 2016. View Article : Google Scholar
34	Liu RZ, Vo TM, Jain S, Choi WS, Garcia E, Monckton EA, Mackey JR and Godbout R: NFIB promotes cell survival by directly suppressing p21 transcription in TP53-mutated triple-negative breast cancer. J Pathol. 247:186–198. 2019. View Article : Google Scholar
35	Lin K, Baritaki S, Militello L, Malaponte G, Bevelacqua Y and Bonavida B: The role of B-RAF mutations in melanoma and the induction of EMT via dysregulation of the NF-ΚB/Snail/RKIP/PTEN circuit. Genes Cancer. 1:409–420. 2010. View Article : Google Scholar
36	Perrot CY, Javelaud D and Mauviel A: Insights into the transforming growth factor-beta signaling pathway in cutaneous melanoma. Ann Dermatol. 25:135–144. 2013. View Article : Google Scholar
37	Wu C, Zhu X, Liu W, Ruan T, Wan W and Tao K: NFIB promotes cell growth, aggressiveness, metastasis and EMT of gastric cancer through the Akt/Stat3 signaling pathway. Oncol Rep. 40:1565–1573. 2018.
38	Ren J, Chen Y, Song H, Chen L and Wang R: Inhibition of ZEB1 reverses EMT and chemoresistance in docetaxel-resistant human lung adenocarcinoma cell line. J Cell Biochem. 114:1395–1403. 2013. View Article : Google Scholar
39	Zhang P, Sun Y and Ma L: ZEB1: At the crossroads of epithelial-mesenchymal transition, metastasis and therapy resistance. Cell Cycle. 14:481–487. 2015. View Article : Google Scholar
40	Spaderna S, Schmalhofer O, Wahlbuhl M, Dimmler A, Bauer K, Sultan A, Hlubek F, Jung A, Strand D, Eger A, et al: The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res. 68:537–544. 2008. View Article : Google Scholar
41	Gheldof A, Hulpiau P, van Roy F, De Craene B and Berx G: Evolutionary functional analysis and molecular regulation of the ZEB transcription factors. Cell Mol Life Sci. 69:2527–2541. 2012. View Article : Google Scholar