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miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A

  • Authors:
    • Feng Zhao
    • Ming Zhong
    • Wenjiang Pei
    • Baoxing Tian
    • Yantao Cai
  • View Affiliations / Copyright

    Affiliations: Department of General Surgery, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200011, P.R. China
    Copyright: © Zhao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 68
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    Published online on: September 9, 2020
       https://doi.org/10.3892/etm.2020.9196
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Abstract

MicroRNAs (miRNAs/miRs) negatively regulate gene expression and participate in various cellular processes. miRNA dysregulation is associated with cancer progression. The present study aimed to identify the miRNAs that participate in breast cancer tumorigenesis and determine the mechanism that underlies this. miRNA microarray data analysis and validation assays indicated that miR‑376c‑3p was downregulated in breast tumour tissues and breast cancer stem cells (BCSCs) compared with adjacent non‑cancerous tissues and MCF‑10A cells, respectively. Ras‑related protein Rab‑2A (RAB2A) was predicted as a target of miR‑376c‑3p, which was confirmed by conducting further experiments. miR‑376c‑3p regulated the BCSC population and the expression of stem cell regulatory genes by targeting RAB2A. By performing mammosphere, Cell Counting Kit‑8, colony formation and transwell invasion assays, it was demonstrated that miR‑376c‑3p also inhibited BCSC self‑renewal, proliferation and invasion by regulating RAB2A expression. Using a xenograft mouse model, it was revealed that miR‑376c‑3p overexpression suppressed breast cancer growth in vivo. In conclusion, the results indicated that miR‑376c‑3p targeted RAB2A to regulate BCSC fate and properties; therefore, miR‑376c‑3p may serve as a potential therapeutic target for breast cancer.
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1 

Kreso A and Dick JE: Evolution of the cancer stem cell model. Cell Stem Cell. 14:275–291. 2014.PubMed/NCBI View Article : Google Scholar

2 

Visvader JE and Lindeman GJ: Cancer stem cells: Current status and evolving complexities. Cell Stem Cell. 10:717–728. 2012.PubMed/NCBI View Article : Google Scholar

3 

Richie RC and Swanson JO: Breast cancer: A review of the literature. J Insurance Med. 35:85–101. 2003.PubMed/NCBI

4 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2018. CA Cancer J Clin. 68:7–30. 2018.PubMed/NCBI View Article : Google Scholar

5 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar

6 

Shimono Y, Mukohyama J, Nakamura S and Minami H: MicroRNA regulation of human breast cancer stem cells. J Clin Med. 5(2)2016.PubMed/NCBI View Article : Google Scholar

7 

Hayes J, Peruzzi PP and Lawler S: MicroRNAs in cancer: Biomarkers, functions and therapy. Trends Mol Med. 20:460–469. 2014.PubMed/NCBI View Article : Google Scholar

8 

Peng Y and Croce CM: The role of MicroRNAs in human cancer. Signal Transduct Target Ther. 1(15004)2016.PubMed/NCBI View Article : Google Scholar

9 

Takahashi RU, Miyazaki H and Ochiya T: The role of microRNAs in the regulation of cancer stem cells. Front Genet. 4(295)2014.PubMed/NCBI View Article : Google Scholar

10 

Garg M: Emerging role of microRNAs in cancer stem cells: Implications in cancer therapy. World J Stem Cells. 7:1078–1089. 2015.PubMed/NCBI View Article : Google Scholar

11 

Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J and Song E: Let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell. 131:1109–1123. 2007.PubMed/NCBI View Article : Google Scholar

12 

Shimono Y, Zabala M, Cho RW, Lobo N, Dalerba P, Qian D, Diehn M, Liu H, Panula SP, Chiao E, et al: Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 138:592–603. 2009.PubMed/NCBI View Article : Google Scholar

13 

Feng ZM, Qiu J, Chen XW, Liao RX, Liao XY, Zhang LP, Chen X, Li Y, Chen ZT and Sun JG: Essential role of miR-200c in regulating self-renewal of breast cancer stem cells and their counterparts of mammary epithelium. BMC Cancer. 15(645)2015.PubMed/NCBI View Article : Google Scholar

14 

Liu S, Patel SH, Ginestier C, Ibarra I, Martin-Trevino R, Bai S, McDermott SP, Shang L, Ke J, Ou SJ, et al: MicroRNA93 regulates proliferation and differentiation of normal and malignant breast stem cells. PLoS Genet. 8(e1002751)2012.PubMed/NCBI View Article : Google Scholar

15 

Taube JH, Malouf GG, Lu E, Sphyris N, Vijay V, Ramachandran PP, Ueno KR, Gaur S, Nicoloso MS, Rossi S, et al: Epigenetic silencing of microRNA-203 is required for EMT and cancer stem cell properties. Sci Rep. 3(2687)2013.PubMed/NCBI View Article : Google Scholar

16 

El Helou R, Pinna G, Cabaud O, Wicinski J, Bhajun R, Guyon L, Rioualen C, Finetti P, Gros A, Mari B, et al: miR-600 Acts as a Bimodal switch that regulates breast cancer stem cell fate through WNT signaling. Cell Rep. 18:2256–2268. 2017.PubMed/NCBI View Article : Google Scholar

17 

Ma S, Tang KH, Chan YP, Lee TK, Kwan PS, Castilho A, Ng I, Man K, Wong N, To KF, et al: miR-130b promotes CD133(+) liver tumor-initiating cell growth and self-renewal via tumor protein 53-induced nuclear protein 1. Cell Stem Cell. 7:694–707. 2010.PubMed/NCBI View Article : Google Scholar

18 

Liu C, Kelnar K, Liu B, Chen X, Calhoun-Davis T, Li H, Patrawala L, Yan H, Jeter C, Honorio S, et al: The microRNA miR-34a inhibits prostate cancer stem cells and metastasis by directly repressing CD44. Natu Med. 17:211–215. 2011.PubMed/NCBI View Article : Google Scholar

19 

Bu P, Chen KY, Chen JH, Wang L, Walters J, Shin YJ, Goerger JP, Sun J, Witherspoon M, Rakhilin N, et al: A microRNA miR-34a-regulated bimodal switch targets Notch in colon cancer stem cells. Cell Stem Cell. 12:602–615. 2013.PubMed/NCBI View Article : Google Scholar

20 

Hwang WL, Jiang JK, Yang SH, Huang TS, Lan HY, Teng HW, Yang CY, Tsai YP, Lin CH, Wang HW and Yang MH: MicroRNA-146a directs the symmetric division of Snail-dominant colorectal cancer stem cells. Nat Cell Biol. 16:268–280. 2014.PubMed/NCBI View Article : Google Scholar

21 

Wang H, Sun T, Hu J, Zhang R, Rao Y, Wang S, Chen R, McLendon RE, Friedman AH, Keir ST, et al: miR-33a promotes glioma-initiating cell self-renewal via PKA and NOTCH pathways. J Clin Invest. 124:4489–4502. 2014.PubMed/NCBI View Article : Google Scholar

22 

Chang WM, Lin YF, Su CY, Peng HY, Chang YC, Lai TC, Wu GH, Hsu YM, Chi LH, Hsiao JR, et al: Dysregulation of RUNX2/Activin-A Axis upon miR-376c downregulation promotes lymph node metastasis in head and neck squamous cell carcinoma. Cancer Res. 76:7140–7150. 2016.PubMed/NCBI View Article : Google Scholar

23 

Tu L, Zhao E, Zhao W, Zhang Z, Tang D, Zhang Y, Wang C, Zhuang C and Cao H: Hsa-miR-376c-3p regulates gastric tumor growth both in vitro and in vivo. Biomed Res Int. 2016(9604257)2016.PubMed/NCBI View Article : Google Scholar

24 

Wang K, Jin J, Ma T and Zhai H: MiR-376c-3p regulates the proliferation, invasion, migration, cell cycle and apoptosis of human oral squamous cancer cells by suppressing HOXB7. Biomed Pharmacother. 91:517–525. 2017.PubMed/NCBI View Article : Google Scholar

25 

Bhavsar SP, Lokke C, Flaegstad T and Einvik C: Hsa-miR-376c-3p targets Cyclin D1 and induces G1-cell cycle arrest in neuroblastoma cells. Oncol Lett. 16:6786–6794. 2018.PubMed/NCBI View Article : Google Scholar

26 

Wang Y, Chang W, Chang W, Chang X, Zhai S, Pan G and Dang S: MicroRNA-376c-3p Facilitates human hepatocellular carcinoma progression via repressing at-rich interaction domain 2. J Cancer. 9:4187–4196. 2018.PubMed/NCBI View Article : Google Scholar

27 

Zhang YH, Fu J, Zhang ZJ, Ge CC and Yi Y: LncRNA-LINC00152 down-regulated by miR-376c-3p restricts viability and promotes apoptosis of colorectal cancer cells. Am J Transl Res. 8:5286–5297. 2016.PubMed/NCBI

28 

Luo ML, Gong C, Chen CH, Hu H, Huang P, Zheng M, Yao Y, Wei S, Wulf G, Lieberman J, et al: The Rab2A GTPase promotes breast cancer stem cells and tumorigenesis via Erk signaling activation. Cell Rep. 11:111–124. 2015.PubMed/NCBI View Article : Google Scholar

29 

Kajiho H, Kajiho Y, Frittoli E, Confalonieri S, Bertalot G, Viale G, Di Fiore PP, Oldani A, Garre M, Beznoussenko GV, et al: RAB2A controls MT1-MMP endocytic and E-cadherin polarized Golgi trafficking to promote invasive breast cancer programs. EMBO Reps. 17:1061–1080. 2016.PubMed/NCBI View Article : Google Scholar

30 

Lin X, Chen W, Wei F, Zhou BP, Hung MC and Xie X: POMC maintains tumor-initiating properties of tumor tissue-derived long-term-cultured breast cancer stem cells. Int J Cancer. 140:2517–2525. 2017.PubMed/NCBI View Article : Google Scholar

31 

Lin X, Chen W, Wei F, Zhou BP, Hung MC and Xie X: Nanoparticle delivery of miR-34a Eradicates Long-term-cultured breast cancer stem cells via targeting C22ORF28 directly. Theranostics. 7:4805–4824. 2017.PubMed/NCBI View Article : Google Scholar

32 

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.PubMed/NCBI View Article : Google Scholar

33 

Huo D, Clayton WM, Yoshimatsu TF, Chen J and Olopade OI: Identification of a circulating microRNA signature to distinguish recurrence in breast cancer patients. Oncotarget. 7:55231–55248. 2016.PubMed/NCBI View Article : Google Scholar

34 

Zhang L, Chen Y, Wang H, Zheng X, Li C and Han Z: miR-376a inhibits breast cancer cell progression by targeting neuropilin-1 NR. OncoTargets Ther. 11:5293–5302. 2018.PubMed/NCBI View Article : Google Scholar

35 

van Schooneveld E, Wildiers H, Vergote I, Vermeulen PB, Dirix LY and Van Laere SJ: Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management. Breast Cancer Res. 17(21)2015.PubMed/NCBI View Article : Google Scholar

36 

Cuk K, Zucknick M, Heil J, Madhavan D, Schott S, Turchinovich A, Arlt D, Rath M, Sohn C, Benner A, et al: Circulating microRNAs in plasma as early detection markers for breast cancer. Int J Cancer. 132:1602–1612. 2013.PubMed/NCBI View Article : Google Scholar

37 

Fan X, Chen W, Fu Z, Zeng L, Yin Y and Yuan H: MicroRNAs, a subpopulation of regulators, are involved in breast cancer progression through regulating breast cancer stem cells. Oncol Lett. 14:5069–5076. 2017.PubMed/NCBI View Article : Google Scholar

38 

Lőrincz P, Tóth S, Benkő P, Lakatos Z, Boda A, Glatz G, Zobel M, Bisi S, Hegedűs K, Takáts S, et al: Rab2 promotes autophagic and endocytic lysosomal degradation. J Cell Biol. 216:1937–1947. 2017.PubMed/NCBI View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Zhao F, Zhong M, Pei W, Tian B and Cai Y: miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A. Exp Ther Med 20: 68, 2020.
APA
Zhao, F., Zhong, M., Pei, W., Tian, B., & Cai, Y. (2020). miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A. Experimental and Therapeutic Medicine, 20, 68. https://doi.org/10.3892/etm.2020.9196
MLA
Zhao, F., Zhong, M., Pei, W., Tian, B., Cai, Y."miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A". Experimental and Therapeutic Medicine 20.5 (2020): 68.
Chicago
Zhao, F., Zhong, M., Pei, W., Tian, B., Cai, Y."miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A". Experimental and Therapeutic Medicine 20, no. 5 (2020): 68. https://doi.org/10.3892/etm.2020.9196
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao F, Zhong M, Pei W, Tian B and Cai Y: miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A. Exp Ther Med 20: 68, 2020.
APA
Zhao, F., Zhong, M., Pei, W., Tian, B., & Cai, Y. (2020). miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A. Experimental and Therapeutic Medicine, 20, 68. https://doi.org/10.3892/etm.2020.9196
MLA
Zhao, F., Zhong, M., Pei, W., Tian, B., Cai, Y."miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A". Experimental and Therapeutic Medicine 20.5 (2020): 68.
Chicago
Zhao, F., Zhong, M., Pei, W., Tian, B., Cai, Y."miR‑376c‑3p modulates the properties of breast cancer stem cells by targeting RAB2A". Experimental and Therapeutic Medicine 20, no. 5 (2020): 68. https://doi.org/10.3892/etm.2020.9196
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