Homeobox B4 inhibits breast cancer cell migration by directly binding to StAR‑related lipid transfer domain protein 13

Zhou,Guangqi; Liu,Xinmei; Xiong,Bin; Sun,Yufang

doi:10.3892/ol.2017.6825

Homeobox B4 inhibits breast cancer cell migration by directly binding to StAR‑related lipid transfer domain protein 13

Authors:
- Guangqi Zhou
- Xinmei Liu
- Bin Xiong
- Yufang Sun
View Affiliations

Affiliations: Department of Breast and Thyroid Surgery, The Affiliated Hospital of Jining Medical University, Jining 272129, P.R. China, Department of Intensive Care Unit, The Affiliated Hospital of Jining Medical University, Jining 272129, P.R. China
Published online on: August 25, 2017 https://doi.org/10.3892/ol.2017.6825
Pages: 4625-4632
Copyright: © Zhou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to investigate the role of homeobox B4 (HOXB4) in breast cancer. Analysis of The Cancer Genome Atlas data revealed that HOXB4 expression was positively associated with expression of the StAR‑related lipid transfer domain protein 13 (STARD13), and the overall survival of patients with breast cancer. Immunohistochemistry and quantitative polymerase chain reaction assays demonstrated that HOXB4 expression was downregulated in breast cancer tissues compared with adjacent normal tissues and was additionally positively associated with STARD13 expression. HOXB4 promoted STARD13 expression in breast cancer cells. Chromatin immunoprecipitation and luciferase reporter assays confirmed that HOXB4 directly bound to the STARD13 promoter. Additionally, HOXB4 inhibited breast cancer cell migration and the epithelial‑mesenchymal transition through the STARD13/Ras homolog (Rho) family member A/Rho associated protein kinase signaling pathway. HOXB4 overexpression enhanced the sensitivity of breast cancer cells to doxorubicin and reversed resistance in doxorubicin‑resistant cells. Overall, the results indicated that HOXB4 inhibited breast cancer cell migration and enhanced the sensitivity of breast cancer cells to doxorubicin by targeting STARD13.

View Figures

View References

1	Giordano SB and Gradishar W: Breast cancer: Updates and advances in 2016. Curr Opin Obstet Gynecol. 29:12–17. 2017. View Article : Google Scholar : PubMed/NCBI
2	Lou PJ, Lai PS, Shieh MJ, Macrobert AJ, Berg K and Bown SG: Reversal of doxorubicin resistance in breast cancer cells by photochemical internalization. Int J Cancer. 119:2692–2698. 2006. View Article : Google Scholar : PubMed/NCBI
3	Helgason CD, Sauvageau G, Lawrence HJ, Largman C and Humphries RK: Overexpression of HOXB4 enhances the hematopoietic potential of embryonic stem cells differentiated in vitro. Blood. 87:2740–2749. 1996.PubMed/NCBI
4	Cusan M, Vegi NM, Mulaw MA, Bamezai S, Kaiser LM, Deshpande AJ, Greif PA, Quintanilla-Fend L, Göllner S, Müller-Tidow C, et al: Controlled stem cell amplification by HOXB4 depends on its unique proline-rich region near the N-terminus. Blood. 129:319–323. 2017. View Article : Google Scholar : PubMed/NCBI
5	Petzold KM, Naumann H and Spagnoli FM: Rho signalling restriction by the RhoGAP Stard13 integrates growth and morphogenesis in the pancreas. Development. 140:126–135. 2013. View Article : Google Scholar : PubMed/NCBI
6	Tang F, Zhang R, He Y, Zou M, Guo L and Xi T: MicroRNA-125b induces metastasis by targeting STARD13 in MCF-7 and MDA-MB-231 breast cancer cells. PLoS One. 7:e354352012. View Article : Google Scholar : PubMed/NCBI
7	Li X, Zheng L, Zhang F, Hu J, Chou J, Liu Y, Xing Y and Xi T: STARD13-correlated ceRNA network inhibits EMT and metastasis of breast cancer. Oncotarget. 7:23197–23211. 2016. View Article : Google Scholar : PubMed/NCBI
8	Zhang H, Wang F and Hu Y: STARD13 promotes hepatocellular carcinoma apoptosis by acting as a ceRNA for Fas. Biotechnol Lett. 39:207–217. 2017. View Article : Google Scholar : PubMed/NCBI
9	Chang S, He S, Qiu G, Lu J, Wang J, Liu J, Fan L, Zhao W and Che X: MicroRNA-125b promotes invasion and metastasis of gastric cancer by targeting STARD13 and NEU1. Tumour Biol. 37:12141–12151. 2016. View Article : Google Scholar : PubMed/NCBI
10	Yang J, Li T, Gao C, Lv X, Liu K, Song H, Xing Y and Xi T: FOXO1 3′UTR functions as a ceRNA in repressing the metastases of breast cancer cells via regulating miRNA activity. FEBS Lett. 588:3218–3224. 2014. View Article : Google Scholar : PubMed/NCBI
11	Zheng L, Li X, Meng X, Chou J, Hu J, Zhang F, Zhang Z, Xing Y, Liu Y and Xi T: Competing endogenous RNA networks of CYP4Z1 and pseudogene CYP4Z2P confer tamoxifen resistance in breast cancer. Mol Cell Endocrinol. 427:133–142. 2016. View Article : Google Scholar : PubMed/NCBI
12	Wang B, Zheng L, Chou J, Li C, Zhang Y, Meng X and Xi T: CYP4Z1 3′UTR represses migration of human breast cancer cells. Biochem Biophys Res Commun. 478:900–907. 2016. View Article : Google Scholar : PubMed/NCBI
13	Nagaraja GM and Kandpal RP: Chromosome 13q12 encoded Rho GTPase activating protein suppresses growth of breast carcinoma cells, and yeast two-hybrid screen shows its interaction with several proteins. Biochem Biophys Res Commun. 313:654–665. 2004. View Article : Google Scholar : PubMed/NCBI
14	Xu T, Zhang J, Chen W, Pan S, Zhi X, Wen L, Zhou Y, Chen BW, Qiu J, Zhang Y, et al: ARK5 promotes doxorubicin resistance in hepatocellular carcinoma via epithelial-mesenchymal transition. Cancer Lett. 377:140–148. 2016. View Article : Google Scholar : PubMed/NCBI
15	Li L, Zhao CT, Cui BL, Wu SL, Liu XD, Su Z, Yang J, Wang W, Cui ZG and Zhao HG: Expression of HOXB4, PRDM16 and HOXA9 in patients with acute myeloid leukemia and its clinical significance. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 24:326–331. 2016.(In Chinese). PubMed/NCBI
16	Sun W and Tang L: MDM2 increases drug resistance in cancer cells by inducing EMT independent of p53. Curr Med Chem. 23:4529–4539. 2016. View Article : Google Scholar : PubMed/NCBI
17	Wang H, Jia XH, Chen JR, Yi YJ, Wang JY, Li YJ and Xie SY: HOXB4 knockdown reverses multidrug resistance of human myelogenous leukemia K562/ADM cells by downregulating P-gp, MRP1 and BCRP expression via PI3K/Akt signaling pathway. Int J Oncol. 49:2529–2537. 2016. View Article : Google Scholar : PubMed/NCBI