HOXA1 upregulation is associated with poor prognosis and tumor progression in breast cancer

Liu,Jintao; Liu,Jinquan; Lu,Xinyi

doi:10.3892/etm.2018.7145

HOXA1 upregulation is associated with poor prognosis and tumor progression in breast cancer

Authors:
- Jintao Liu
- Jinquan Liu
- Xinyi Lu
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Affiliations: Department of Breast Surgery, Dalian Central Hospital Affiliated to Dalian Medical University, Dalian, Liaoning 116033, P.R. China, Department of Clinical Medicine, Datong University School of Medicine, Datong, Shanxi 037009, P.R. China
Published online on: December 28, 2018 https://doi.org/10.3892/etm.2018.7145
Pages: 1896-1902

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Abstract

Breast cancer (BC) is the most commonly diagnosed cancer and the second leading cause of cancer‑associated mortality among females worldwide. As a member of the homeobox (HOX) gene family, HOXA1 is involved in tumor progression and prognosis in several types of human cancer. However, the clinical significance and biological functions of HOXA1 in BC remains unknown. The current study assessed the expression of HOXA1 in BC tissues and cells via western blotting and reverse transcription‑quantitative polymerase chain reaction. The association between HOXA1 expression and the clinicopathological features of patients with BC was analyzed using the Chi‑square test. The overall survival of patients was calculated using the Kaplan‑Meier method and examined using the log‑rank test. Cell proliferation was examined via an MTT assay. Cell cycle distribution and cell apoptosis were analyzed using flow cytometry. The current study demonstrated that HOXA1 mRNA and protein expression was upregulated in BC. In addition, HOXA1 overexpression was associated with poor prognosis and advanced clinicopathological features in patients with BC. Furthermore, knockdown of HOXA1 significantly inhibited cell proliferation by enhancing cell apoptosis and cell cycle arrest in BC cells, which was accompanied with aberrant expression of cell cycle and apoptosis‑associated proteins, cyclin D1, B‑cell lymphoma 2 (Bcl‑2) and Bcl‑2‑like protein 4. Taken together, the results suggested that HOXA1 may serve as a novel prognostic marker and therapeutic target in BC.

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1	Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018. View Article : Google Scholar : PubMed/NCBI
2	DeSantis CE, Ma J, Goding Sauer A, Newman LA and Jemal A: Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 67:439–448. 2017. View Article : Google Scholar : PubMed/NCBI
3	Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ and He J: Cancer statistics in China, 2015. CA Cancer J Clin. 66:115–132. 2016. View Article : Google Scholar : PubMed/NCBI
4	Qin C, Zhao Y, Gong C and Yang Z: MicroRNA-154/ADAM9 axis inhibits the proliferation, migration and invasion of breast cancer cells. Oncol Lett. 14:6969–6975. 2017.PubMed/NCBI
5	Gehring WJ and Hiromi Y: Homeotic genes and the homeobox. Annu Rev Genet. 20:147–173. 1986. View Article : Google Scholar : PubMed/NCBI
6	Scott MP: Vertebrate homeobox gene nomenclature. Cell. 71:551–553. 1992. View Article : Google Scholar : PubMed/NCBI
7	Yuan C, Zhu X, Han Y, Song C, Liu C, Lu S, Zhang M, Yu F, Peng Z and Zhou C: Elevated HOXA1 expression correlates with accelerated tumor cell proliferation and poor prognosis in gastric cancer partly via cyclin D1. J Exp Clin Cancer Res. 35:152016. View Article : Google Scholar : PubMed/NCBI
8	Wang H, Liu G, Shen D, Ye H, Huang J, Jiao L and Sun Y: HOXA1 enhances the cell proliferation, invasion and metastasis of prostate cancer cells. Oncol Rep. 34:1203–1210. 2015. View Article : Google Scholar : PubMed/NCBI
9	Zha TZ, Hu BS, Yu HF, Tan YF, Zhang Y and Zhang K: Overexpression of HOXA1 correlates with poor prognosis in patients with hepatocellular carcinoma. Tumour Biol. 33:2125–2134. 2012. View Article : Google Scholar : PubMed/NCBI
10	Leong AS and Zhuang Z: The changing role of pathology in breast cancer diagnosis and treatment. Pathobiology. 78:99–114. 2011. View Article : Google Scholar : PubMed/NCBI
11	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
12	Li Y, Lv M, Song Z, Lou Z, Wang R and Zhuang M: Long non-coding RNA NNT-AS1 affects progression of breast cancer through miR-142-3p/ZEB1 axis. Biomed Pharmacother. 103:939–946. 2018. View Article : Google Scholar : PubMed/NCBI
13	Li P, Dong J, Zhou X, Sun W, Huang H, Chen T, Ye B, Zheng Z and Lu M: Expression patterns of microRNA-329 and its clinical performance in diagnosis and prognosis of breast cancer. Onco Targets Ther. 10:5711–5718. 2017. View Article : Google Scholar : PubMed/NCBI
14	Teo WW, Merino VF, Cho S, Korangath P, Liang X, Wu RC, Neumann NM, Ewald AJ and Sukumar S: HOXA5 determines cell fate transition and impedes tumor initiation and progression in breast cancer through regulation of E-cadherin and CD24. Oncogene. 35:5539–5551. 2016. View Article : Google Scholar : PubMed/NCBI
15	Hayashida T, Takahashi F, Chiba N, Brachtel E, Takahashi M, Godin-Heymann N, Gross KW, Vivanco Md, Wijendran V, Shioda T, et al: HOXB9, a gene overexpressed in breast cancer, promotes tumorigenicity and lung metastasis. Proc Natl Acad Sci USA. 107:1100–1105. 2010. View Article : Google Scholar : PubMed/NCBI
16	Zhang Y, Yang C, Zhang M, Liu H, Gong C, Zhang J, Xu S, Zou J, Kai Y and Li Y: Interleukin enhancer-binding factor 3 and HOXC8 co-activate cadherin 11 transcription to promote breast cancer cells proliferation and migration. Oncotarget. 8:107477–107491. 2017.PubMed/NCBI
17	Taminiau A, Draime A, Tys J, Lambert B, Vandeputte J, Nguyen N, Renard P, Geerts D and Rezsöhazy R: HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-κB pathway in a transcription-independent manner. Nucleic Acids Res. 44:7331–7349. 2016.PubMed/NCBI
18	Wang JG, Tang WP, Liao MC, Liu YP and Ai XH: MiR-99a suppresses cell invasion and metastasis in nasopharyngeal carcinoma through targeting HOXA1. Onco Targets Ther. 10:753–761. 2017. View Article : Google Scholar : PubMed/NCBI
19	Ni LY, Zhao JD, Lu YH, Li W, Li BL, Wang XC and Meng QG: MicroRNA-30c suppressed giant-cell tumor of bone cell metastasis and growth via targeting HOXA1. Eur Rev Med Pharmacol Sci. 21:4819–4827. 2017.PubMed/NCBI
20	Xiao F, Bai Y, Chen Z, Li Y, Luo L, Huang J, Yang J, Liao H and Guo L: Downregulation of HOXA1 gene affects small cell lung cancer cell survival and chemoresistance under the regulation of miR-100. Eur J Cancer. 50:1541–1554. 2014. View Article : Google Scholar : PubMed/NCBI