HIF‑1α and MBP1 are associated with the progression of breast cancer cells by repressing β‑catenin transcription

Zhuang,Ying; Li,Xiang; Zhan,Peng; Pi,Guoliang; Wen,Gu

doi:10.3892/or.2022.8361

HIF‑1α and MBP1 are associated with the progression of breast cancer cells by repressing β‑catenin transcription

Authors:
- Ying Zhuang
- Xiang Li
- Peng Zhan
- Guoliang Pi
- Gu Wen
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Affiliations: Department of Breast Surgery, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, P.R. China
Published online on: July 5, 2022 https://doi.org/10.3892/or.2022.8361
Article Number: 149
Copyright: © Zhuang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer (BC) is a common type of tumor. Numerous patients are diagnosed and treated in the early stages of the disease; however, the recurrence rate remains high. Therefore, identifying sensitive and specific tumor markers to prevent and treat BC is essential. c‑Myc promoter binding protein 1 (MBP1) is a regulatory molecule located in the cell nucleus. It targets and regulates the expression of various cell proliferation‑, apoptosis‑ and tumor‑associated genes. MBP1 expression in BC tissues was detected using immunohistochemistry and further validated in BC and normal human cell lines using RT‑qPCR and western blot analysis. Low MBP1 expression, in clinical samples of BC, was associated with a poor prognosis of BC (n=50). MBP1 overexpression effectively inhibited the growth and metastasis of xenograft tumors in vivo. Cell counting kit‑8 assays confirmed that the proliferation of the BC cell lines was significantly increased following knockdown of MBP1 expression, while overexpression of MBP1 could significantly inhibit the proliferation of the BC cell lines. Mechanistically, a dual‑luciferase assay was used to confirm that MBP1 was the key transcriptional regulator of β‑catenin. In addition, MBP1 transcription and hypoxia‑inducible factor (HIF‑1α) induction were associated. By regulating the hypoxic microenvironmental state in the MDA231 and MCF7 cell lines, it was demonstrated that MBP1 served as a hypoxia‑responsive factor and could be a new target for tumor therapy. Taken together, these results suggested that MBP1, as a potential tumor marker associated with prognosis of BC and may serve as a therapeutic target for BC. Moreover, MBP1 plays a critical role in inhibiting the growth and progression of BC cell lines.

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1	Ferlay J, Colombet M, Soerjomataram I, Dyba T, Randi G, Bettio M, Gavin A, Visser O and Bray F: Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 103:356–387. 2018. View Article : Google Scholar : PubMed/NCBI
2	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2020. CA Cancer J Clin. 70:7–30. 2020. View Article : Google Scholar : PubMed/NCBI
3	Li J, Chen Z, Su K and Zeng J: Clinicopathological classification and traditional prognostic indicators of breast cancer. Int J Clin Exp Pathol. 8:8500–8505. 2015.PubMed/NCBI
4	Nagini S: Breast cancer: Current molecular therapeutic targets and new players. Anticancer Agents Med Chem. 17:152–163. 2017. View Article : Google Scholar : PubMed/NCBI
5	Chiappa C, Rovera F, Rausei S, Del Ferraro S, Fachinetti A, Lavazza M, Marchionini V, Arlant V, Tanda ML, Piantanida E, et al: Breast cancer and thyroid diseases: Analysis of 867 consecutive cases. J Endocrinol Invest. 40:179–184. 2017. View Article : Google Scholar : PubMed/NCBI
6	Hammerl D, Smid M, Timmermans AM, Sleijfer S, Martens JWM and Debets R: Breast cancer genomics and immuno-oncological markers to guide immune therapies. Semin Cancer Biol. 52:178–188. 2018. View Article : Google Scholar : PubMed/NCBI
7	Bates JP, Derakhshandeh R, Jones L and Webb TJ: Mechanisms of immune evasion in breast cancer. BMC Cancer. 18:5562018. View Article : Google Scholar : PubMed/NCBI
8	Pérez-González O, Cuéllar-Guzmán LF, Soliz J and Cata JP: Impact of regional anesthesia on recurrence, metastasis, and immune response in breast cancer surgery: A systematic review of the literature. Reg Anesth Pain Med. 42:751–756. 2017. View Article : Google Scholar : PubMed/NCBI
9	Liu Z, Zhang A, Zheng L, Johnathan AF, Zhang J and Zhang G: The biological significance and regulatory mechanism of c-Myc Binding Protein 1 (MBP-1). Int J Mol Sci. 19:38682018. View Article : Google Scholar : PubMed/NCBI
10	Hsu KW, Hsieh RH, Wu CW, Chi CW, Lee YH, Kuo ML, Wu KJ and Yeh TS: MBP-1 suppresses growth and metastasis of gastric cancer cells through COX-2. Mol Biol Cell. 20:5127–37. 2009. View Article : Google Scholar : PubMed/NCBI
11	Cancemi P, Buttacavoli M, Roz E and Feo S: Expression of Alpha-Enolase (ENO1), Myc Promoter-Binding Protein-1 (MBP-1) and Matrix Metalloproteinases (MMP-2 and MMP-9) Reflect the Nature and Aggressiveness of Breast Tumors. Int J Mol Sci. 20:39522019. View Article : Google Scholar : PubMed/NCBI
12	Fan X, Solomon H, Schwarz K, Kew MC, Ray RB and Di Bisceglie AM: Expression of c-myc promoter binding protein (MBP-1), a novel eukaryotic repressor gene, in cirrhosis and human hepatocellular carcinoma. Dig Dis Sci. 46:563–566. 2001. View Article : Google Scholar : PubMed/NCBI
13	Kanda T, Raychoudhuri A, Steele R, Sagartz JE, West C and Ray RB: MBP-1 inhibits breast cancer growth and metastasis in immunocompetent mice. Cancer Res. 69:9354–9359. 2009. View Article : Google Scholar : PubMed/NCBI
14	Ray RB, Steele R, Seftor E and Hendrix M: Human breast carcinoma cells transfected with the gene encoding a c-myc promoter-binding protein (MBP-1) inhibits tumors in nude mice. Cancer Res. 55:3747–3751. 1995.PubMed/NCBI
15	Lo Presti M, Ferro A, Contino F, Mazzarella C, Sbacchi S, Roz E, Lupo C, Perconti G, Giallongo A, Migliorini P, et al: Myc promoter-binding protein-1 (MBP-1) is a novel potential prognostic marker in invasive ductal breast carcinoma. PLoS One. 5:e129612010. View Article : Google Scholar : PubMed/NCBI
16	Ray RB and Steele R: Separate domains of MBP-1 involved in c-myc promoter binding and growth suppressive activity. Gene. 186:175–80. 1997. View Article : Google Scholar : PubMed/NCBI
17	Ray R, Sheikh S, Fontana J and Miller D: Human breast-carcinoma cells show correlation in expression of C-myc oncogene and the C-myc binding-protein (mbp-1). Int J Oncol. 5:1433–1436. 1994.PubMed/NCBI
18	Zhuang Y, Li X, Zhan P, Pi G and Wen G: MMP11 promotes the proliferation and progression of breast cancer through stabilizing Smad2 protein. Oncol Rep. 45:162021. View Article : Google Scholar : PubMed/NCBI
19	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 : PubMed/NCBI
20	Huang P, Yan R, Zhang X, Wang L, Ke X and Qu Y: Activating Wnt/β-catenin signaling pathway for disease therapy: Challenges and opportunities. Pharmacol Ther. 196:79–90. 2019. View Article : Google Scholar : PubMed/NCBI
21	Macklin PS, McAuliffe J, Pugh CW and Yamamoto A: Hypoxia and HIF pathway in cancer and the placenta. Placenta. 56:8–13. 2017. View Article : Google Scholar : PubMed/NCBI
22	Katoh M: Multi-layered prevention and treatment of chronic inflammation, organ fibrosis and cancer associated with canonical WNT/β-catenin signaling activation (Review). Int J Mol Med. 42:713–725. 2018.PubMed/NCBI
23	Krishnamurthy N and Kurzrock R: Targeting the Wnt/beta-catenin pathway in cancer: Update on effectors and inhibitors. Cancer Treat Rev. 62:50–60. 2018. View Article : Google Scholar : PubMed/NCBI
24	Steele R, Mott JL and Ray RB: MBP-1 upregulates miR-29b that represses Mcl-1, collagens, and matrix-metalloproteinase-2 in prostate cancer cells. Genes Cancer. 1:381–387. 2010. View Article : Google Scholar : PubMed/NCBI
25	Hsu KW, Wang AM, Ping YH, Huang KH, Huang TT, Lee HC, Lo SS, Chi CW and Yeh TS: Downregulation of tumor suppressor MBP-1 by microRNA-363 in gastric carcinogenesis. Carcinogenesis. 35:208–217. 2014. View Article : Google Scholar : PubMed/NCBI
26	Jing X, Yang F, Shao C, Wei K, Xie M, Shen H and Shu Y: Role of hypoxia in cancer therapy by regulating the tumor microenvironment. Mol Cancer. 18:1572019. View Article : Google Scholar : PubMed/NCBI
27	Tan M, Gu Q, He H, Pamarthy D, Semenza GL and Sun Y: SAG/ROC2/RBX2 is a HIF-1 target gene that promotes HIF-1 alpha ubiquitination and degradation. Oncogene. 27:1404–1411. 2008. View Article : Google Scholar : PubMed/NCBI