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World Journal of Surgical Oncology

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Open Access 01-12-2021 | Breast Cancer | Research

MicroRNA-638 inhibits the progression of breast cancer through targeting HOXA9 and suppressing Wnt/β-cadherin pathway

Authors: Qian Xu, Qianqian Zhang, Mengli Dong, Yuan Yu

Published in: World Journal of Surgical Oncology | Issue 1/2021

Abstract

Background

Previous studies had shown that microRNA-638 (miR-638) exhibited different effects in malignant tumors. Moreover, the function of miR-638 has not been reported in breast cancer. Hence, we designed this research to explore the function of miR-638 in breast cancer.

Methods

Firstly, miR-638 expressions were measured in breast cancer tissues via RT-qPCR. Protein expressions were detected through immunocytochemical (IHC) assay and western blot analysis. Then, Cell Counting Kit-8 (CCK-8) assay and Transwell assay were conducted to observe proliferation and motility of the cells. Dual luciferase assay was performed to confirm the binding site between miR-638 and Homeobox protein Hox-A9 (HOXA9).

Results

Reduced expression of miR-638 was detected in breast cancer. And low miR-638 expression was related to poor prognosis in patients with breast cancer. Functionally, the viability, migration, and invasion of the breast cancer cells were suppressed by miR-638 overexpression. Furthermore, miR-638 can directly bind to HOXA9, and increased expression of HOXA9 was also detected in breast cancer. In particular, HOXA9 upregulation can impair anti-tumor effect of miR-638 in breast cancer, and miR-638 can hinder the Wnt/β-cadherin pathway and epithelial-mesenchymal transition (EMT) in breast cancer.

Conclusion

miR-638 inhibits breast cancer progression through binding to HOXA9.

Yang J, Zhang JY, Chen J, Chen C, Song XM, Xu Y, et al. Prognostic role of microRNA-145 in various human malignant neoplasms: a meta-analysis of 18 related studies. World J Surg Oncol. 2014;12(1):254. https://doi.org/10.1186/1477-7819-12-254.CrossRefPubMedPubMedCentral

Liang F, Qu H, Lin Q, Yang Y, Ruan X, Zhang B, et al. Molecular biomarkers screened by next-generation RNA sequencing for non-sentinel lymph node status prediction in breast cancer patients with metastatic sentinel lymph nodes. World J Surg Oncol. 2015;13(1):258. https://doi.org/10.1186/s12957-015-0642-2.CrossRefPubMedPubMedCentral

Qiu Z, Wang L, Liu H. Hsa_circ_0001982 promotes the progression of breast cancer through miR-1287-5p/MUC19 axis under hypoxia. World J Surg Oncol. 2021;19(1):161. https://doi.org/10.1186/s12957-021-02273-8.CrossRefPubMedPubMedCentral

Mao XH, Ye Q, Zhang GB, Jiang JY, Zhao HY, Shao YF, et al. Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer. World J Surg Oncol. 2021;19(1):29. https://doi.org/10.1186/s12957-021-02124-6.CrossRefPubMedPubMedCentral

Perri F, Longo F, Giuliano M, Sabbatino F, Favia G, Ionna F, et al. Epigenetic control of gene expression: potential implications for cancer treatment. Crit Rev Oncol Hematol. 2017;111:166–72. https://doi.org/10.1016/j.critrevonc.2017.01.020.CrossRefPubMed

Li Y, Shan F, Chen J. Lipid raft-mediated miR-3908 inhibition of migration of breast cancer cell line MCF-7 by regulating the interactions between AdipoR1 and Flotillin-1. World J Surg Oncol. 2017;15(1):69. https://doi.org/10.1186/s12957-017-1120-9.CrossRefPubMedPubMedCentral

Zhou M, Zhong L, Xu W, Sun Y, Zhang Z, Zhao H, et al. Discovery of potential prognostic long non-coding RNA biomarkers for predicting the risk of tumor recurrence of breast cancer patients. Sci Rep. 2016;6(1):31038. https://doi.org/10.1038/srep31038.CrossRefPubMedPubMedCentral

Wang Y, Zhang Z, Wang J. MicroRNA-384 inhibits the progression of breast cancer by targeting ACVR1. Oncol Rep. 2018;39(6):2563–74. https://doi.org/10.3892/or.2018.6385.CrossRefPubMedPubMedCentral

Zhang J, He Y, Yu Y, Chen X, Cui G, Wang W, et al. Upregulation of miR-374a promotes tumor metastasis and progression by downregulating LACTB and predicts unfavorable prognosis in breast cancer. Cancer Med. 2018;7(7):3351–62. https://doi.org/10.1002/cam4.1576.CrossRefPubMedCentral

10.

Wang Y, Li J, Dai L, Zheng J, Yi Z, Chen L. MiR-17-5p may serve as a novel predictor for breast cancer recurrence. Cancer Biomark. 2018;22(4):721–6. https://doi.org/10.3233/CBM-181228.CrossRefPubMed

11.

Shen Y, Chen H, Gao L, Zhang W, He J, Yang X, et al. MiR-638 acts as a tumor suppressor gene in gastric cancer. Oncotarget. 2017;8(64):108170–80. https://doi.org/10.18632/oncotarget.22567.CrossRefPubMedPubMedCentral

12.

Bhattacharya A, Schmitz U, Raatz Y, Schonherr M, Kottek T, Schauer M, et al. miR-638 promotes melanoma metastasis and protects melanoma cells from apoptosis and autophagy. Oncotarget. 2015;6(5):2966–80. https://doi.org/10.18632/oncotarget.3070.CrossRefPubMed

13.

Wang F, Lou JF, Cao Y, Shi XH, Wang P, Xu J, et al. miR-638 is a new biomarker for outcome prediction of non-small cell lung cancer patients receiving chemotherapy. Exp Mol Med. 2015;47:e162.

14.

Zhao G, Li Y, Wang T. Potentiation of docetaxel sensitivity by miR-638 via regulation of STARD10 pathway in human breast cancer cells. Biochem Biophys Res Commun. 2017;487(2):255–61. https://doi.org/10.1016/j.bbrc.2017.04.045.CrossRefPubMed

15.

Li CY, Cui ZS, Lu Y, Zhang Y, Gao J, Wang EH. The roles of important molecules of Wnt signaling pathway in non-small-cell lung cancer. Zhonghua Bing Li Xue Za Zhi. 2005;34(9):599–600.PubMed

16.

Umbreit C, Aderhold C, Faber A, Sommer JU, Sauter A, Hofheinz RD, et al. Unexpected alteration of beta-catenin and c-KIT expression by 5-FU and docetaxel in p16-positive squamous cell carcinoma compared to HPV-negative HNSCC cells in vitro. Anticancer Res. 2013;33(6):2457–65.PubMed

17.

Anastas JN, Moon RT. WNT signalling pathways as therapeutic targets in cancer. Nat Rev Cancer. 2013;13(1):11–26. https://doi.org/10.1038/nrc3419.CrossRefPubMed

18.

Zardawi SJ, O’Toole SA, Sutherland RL, Musgrove EA. Dysregulation of Hedgehog, Wnt and Notch signalling pathways in breast cancer. Histol Histopathol. 2009;24(3):385–98. https://doi.org/10.14670/HH-24.385.CrossRefPubMed

19.

Costa BM, Smith JS, Chen Y, Chen J, Phillips HS, Aldape KD, et al. Reversing HOXA9 oncogene activation by PI3K inhibition: epigenetic mechanism and prognostic significance in human glioblastoma. Cancer Res. 2010;70(2):453–62. https://doi.org/10.1158/0008-5472.CAN-09-2189.CrossRefPubMedPubMedCentral

20.

Brumatti G, Salmanidis M, Kok CH, Bilardi RA, Sandow JJ, Silke N, et al. HoxA9 regulated Bcl-2 expression mediates survival of myeloid progenitors and the severity of HoxA9-dependent leukemia. Oncotarget. 2013;4(11):1933–47. https://doi.org/10.18632/oncotarget.1306.CrossRefPubMedPubMedCentral

21.

Gilbert PM, Mouw JK, Unger MA, Lakins JN, Gbegnon MK, Clemmer VB, et al. HOXA9 regulates BRCA1 expression to modulate human breast tumor phenotype. J Clin Invest. 2010;120(5):1535–50. https://doi.org/10.1172/JCI39534.CrossRefPubMedPubMedCentral

22.

Donaldson IJ, Amin S, Hensman JJ, Kutejova E, Rattray M, Lawrence N, et al. Genome-wide occupancy links Hoxa2 to Wnt-beta-catenin signaling in mouse embryonic development. Nucleic Acids Res. 2012;40(9):3990–4001. https://doi.org/10.1093/nar/gkr1240.CrossRefPubMedPubMedCentral

23.

Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Invest. 2009;119(6):1420–8. https://doi.org/10.1172/JCI39104.CrossRefPubMedPubMedCentral

24.

Han M, Wang Y, Guo G, Li L, Dou D, Ge X, et al. microRNA-30d mediated breast cancer invasion, migration, and EMT by targeting KLF11 and activating STAT3 pathway. J Cell Biochem. 2018;119(10):8138–45. https://doi.org/10.1002/jcb.26767.CrossRefPubMed

25.

Zuo TT, Zheng RS, Zeng HM, Zhang SW, Chen WQ. Female breast cancer incidence and mortality in China, 2013. Thorac Cancer. 2017;8(3):214–8. https://doi.org/10.1111/1759-7714.12426.CrossRefPubMedPubMedCentral

26.

Liu H, Huang X, Ye T. MiR-22 down-regulates the proto-oncogene ATP citrate lyase to inhibit the growth and metastasis of breast cancer. Am J Transl Res. 2018;10(3):659–69.PubMedPubMedCentral

27.

Du HY, Liu B. MiR-1271 as a tumor suppressor in breast cancer proliferation and progression via targeting SPIN1. Eur Rev Med Pharmacol Sci. 2018;22(9):2697–706. https://doi.org/10.26355/eurrev_201805_14966.CrossRefPubMed

28.

Mansoori B, Duijf PHG, Mohammadi A, Safarzadeh E, Ditzel HJ, Gjerstorff MF, et al. MiR-142-3p targets HMGA2 and suppresses breast cancer malignancy. Life Sci. 2021;276:119431. https://doi.org/10.1016/j.lfs.2021.119431.CrossRefPubMed

29.

Cheng J, Chen Y, Zhao P, Li N, Lu J, Li J, et al. Dysregulation of miR-638 in hepatocellular carcinoma and its clinical significance. Oncol Lett. 2017;13(5):3859–65. https://doi.org/10.3892/ol.2017.5882.CrossRefPubMedPubMedCentral

30.

Shi M, Jiang Y, Yang L, Yan S, Wang YG, Lu XJ. Decreased levels of serum exosomal miR-638 predict poor prognosis in hepatocellular carcinoma. J Cell Biochem. 2018;119(6):4711–6. https://doi.org/10.1002/jcb.26650.CrossRefPubMed

31.

Zhang J, Fei B, Wang Q, Song M, Yin Y, Zhang B, et al. MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma. Oncotarget. 2014;5(23):12083–96. https://doi.org/10.18632/oncotarget.2499.CrossRefPubMedPubMedCentral

32.

Ma K, Pan X, Fan P, He Y, Gu J, Wang W, et al. Loss of miR-638 in vitro promotes cell invasion and a mesenchymal-like transition by influencing SOX2 expression in colorectal carcinoma cells. Mol Cancer. 2014;13(1):118. https://doi.org/10.1186/1476-4598-13-118.CrossRefPubMedPubMedCentral

33.

Wei H, Zhang JJ, Tang QL. MiR-638 inhibits cervical cancer metastasis through Wnt/beta-catenin signaling pathway and correlates with prognosis of cervical cancer patients. Eur Rev Med Pharmacol Sci. 2017;21(24):5587–93. https://doi.org/10.26355/eurrev_201712_13999.CrossRefPubMed

34.

Collins CT, Hess JL. Role of HOXA9 in leukemia: dysregulation, cofactors and essential targets. Oncogene. 2016;35(9):1090–8. https://doi.org/10.1038/onc.2015.174.CrossRefPubMed

35.

Liu Y, Zheng W, Song Y, Ma W, Yin H. Low expression of miR-196b enhances the expression of BCR-ABL1 and HOXA9 oncogenes in chronic myeloid leukemogenesis. PLoS One. 2013;8(7):e68442. https://doi.org/10.1371/journal.pone.0068442.CrossRefPubMedPubMedCentral

36.

Shen WF, Hu YL, Uttarwar L, Passegue E, Largman C. MicroRNA-126 regulates HOXA9 by binding to the homeobox. Mol Cell Biol. 2008;28(14):4609–19. https://doi.org/10.1128/MCB.01652-07.CrossRefPubMedPubMedCentral

37.

Hu YL, Fong S, Largman C, Shen WF. HOXA9 regulates miR-155 in hematopoietic cells. Nucleic Acids Res. 2010;38(16):5472–8. https://doi.org/10.1093/nar/gkq337.CrossRefPubMedPubMedCentral

38.

Yu SL, Lee DC, Sohn HA, Lee SY, Jeon HS, Lee JH, et al. Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells. Mol Carcinog. 2016;55(12):1915–26. https://doi.org/10.1002/mc.22439.CrossRefPubMed

39.

Wang X, Bu J, Liu X, Wang W, Mai W, Lv B, et al. miR-133b suppresses metastasis by targeting HOXA9 in human colorectal cancer. Oncotarget. 2017;8(38):63935–48. https://doi.org/10.18632/oncotarget.19212.CrossRefPubMedPubMedCentral

40.

Zhang ZF, Wang YJ, Fan SH, Du SX, Li XD, Wu DM, et al. MicroRNA-182 downregulates Wnt/beta-catenin signaling, inhibits proliferation, and promotes apoptosis in human osteosarcoma cells by targeting HOXA9. Oncotarget. 2017;8(60):101345–61. https://doi.org/10.18632/oncotarget.21167.CrossRefPubMedPubMedCentral

41.

Jiang J, Yang X, He X, Ma W, Wang J, Zhou Q, et al. MicroRNA-449b-5p suppresses the growth and invasion of breast cancer cells via inhibiting CREPT-mediated Wnt/β-catenin signaling. Chem Biol Interact. 2019;302:74–82. https://doi.org/10.1016/j.cbi.2019.02.004.CrossRefPubMed

Title: MicroRNA-638 inhibits the progression of breast cancer through targeting HOXA9 and suppressing Wnt/β-cadherin pathway
Authors: Qian Xu
Qianqian Zhang
Mengli Dong
Yuan Yu
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: World Journal of Surgical Oncology / Issue 1/2021
Electronic ISSN: 1477-7819
DOI: https://doi.org/10.1186/s12957-021-02363-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

MicroRNA-638 inhibits the progression of breast cancer through targeting HOXA9 and suppressing Wnt/β-cadherin pathway

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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