GUSBP11 Inhibited The Progression of Triple Negative Breast Cancer via Targeting The miR-579-3p/SPNS2 Axis

Document Type : Original Article


Department of General Surgery, Jinshan Hospital, Fudan University, Shanghai, China


Objective: Growing evidences have exposed the important roles of long noncoding RNAs (lncRNAs) in the triple negative breast cancer (TNBC) inhibition. The function of glucuronidase beta pseudogene 11 (GUSBP11) in the TNBC occurrence remains obscure. To detect the function of GUSBP11 in TNBC progression and explore its downstream molecular mechanism.
Materials and Methods: In this experimental study, using quantitative reverse transcription real-time polymerase chain reaction (RT-qPCR), we measured the GUSBP11 expression in the TNBC cell lines. Gain-of-function assays, including colony formation, flow cytometry, and western blot were used to identify the probable effects of GUSBP11 overexpression on the malignant behaviors of TNBC cell lines. Moreover, mechanism assays, including RNA immunoprecipitation (RIP), RNA pull down and luciferase reporter assays were taken to measure the possible mechanism of GUSBP11 in the TNBC cell lines.
Results: GUSBP11 expressed at a low RNA level in the TNBC cell lines. Overexpression of GUSBP11 RNA expression inhibited the proliferation, migration, epithelial-to-mesenchymal transition (EMT) and stemness while elevated the apoptosis of the TNBC cell lines. GUSBP11 positively regulated the expression of sphingolipid transporter 2 (SPNS2) via acting as a competing endogenous RNA (ceRNA) of miR-579-3p, thereby suppressing the development of TNBC cell lines.
Conclusion: GUSBP11 impedes TNBC progression via modulating the miR-579-3p/SPNS2 axis.


  1. DeSantis C, Siegel R, Bandi P, Jemal A. Breast cancer statistics, 2011. CA Cancer J Clin. 2011; 61(6): 409-418.
  2. Woolston C. Breast cancer. Nature. 2015; 527(7578): S101.
  3. Kumar P, Aggarwal R. An overview of triple-negative breast cancer. Arch Gynecol Obstet. 2016; 293(2): 247-269.
  4. Fahad Ullah M. Breast cancer: current perspectives on the disease status. Adv Exp Med Biol. 2019; 1152: 51-64.
  5. Maughan KL, Lutterbie MA, Ham PS. Treatment of breast cancer. Am Fam Physician. 2010; 81(11): 1339-1346.
  6. Wang J, Zhu S, Meng N, He Y, Lu R, Yan GR. ncRNA-encoded peptides or proteins and cancer. Mol Ther. 2019; 27(10): 1718- 1725.
  7. Anastasiadou E, Jacob LS, Slack FJ. Non-coding RNA networks in cancer. Nat Rev Cancer. 2018; 18(1): 5-18.
  8. Ferrè F, Colantoni A, Helmer-Citterich M. Revealing protein-lncRNA interaction. Brief Bioinform. 2016; 17(1): 106-116.
  9. Li J, Li L, Yuan H, Huang XW, Xiang T, Dai S. Up-regulated lncRNA GAS5 promotes chemosensitivity and apoptosis of triple-negative breast cancer cells. Cell Cycle. 2019; 18(16): 1965-1975.
  10. Song X, Liu Z, Yu Z. LncRNA NEF is downregulated in triple negative breast cancer and correlated with poor prognosis. Acta Biochim Biophys Sin (Shanghai). 2019; 51(4): 386-392.
  11. Weng YS, Tseng HY, Chen YA, Shen PC, Al Haq AT, Chen LM, et al. MCT-1/miR-34a/IL-6/IL-6R signaling axis promotes EMT progression, cancer stemness and M2 macrophage polarization in triple-negative breast cancer. Mol Cancer. 2019; 18(1): 42.
  12. Zhang B, Shetti D, Fan C, Wei K. miR-29b-3p promotes progression of MDA-MB-231 triple-negative breast cancer cells through downregulating TRAF3. Biol Res. 2019; 52(1): 38.
  13. Xiong H, Yan T, Zhang W, Shi F, Jiang X, Wang X, et al. miR-613inhibits cell migration and invasion by downregulating Daam1 in triple-negative breast cancer. Cell Signal. 2018; 44: 33-42.
  14. Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010; 79: 351-379.
  15. Fattore L, Mancini R, Acunzo M, Romano G, Laganà A, Pisanu ME, et al. miR-579-3p controls melanoma progression and resistance to target therapy. Proc Natl Acad Sci USA. 2016; 113(34): E5005-13.
  16. Tang W, Zhou W, Xiang L, Wu X, Zhang P, Wang J, et al. The p300/ YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer. Nat Commun. 2019; 10(1): 663.
  17. Uchida Y, Chiba T, Kurimoto R, Asahara H. Post-transcriptional regulation of inflammation by RNA-binding proteins via cis-elements of mRNAs. J Biochem. 2019; 166(5): 375-382.
  18. Boyce AKJ, Epp AL, Nagarajan A, Swayne LA. Transcriptional and post-translational regulation of pannexins. Biochim Biophys Acta Biomembr. 2018; 1860(1): 72-82.
  19. Fu J, Dong G, Shi H, Zhang J, Ning Z, Bao X, et al. LncRNA MIR503HG inhibits cell migration and invasion via miR-103/OLFM4 axis in triple negative breast cancer. J Cell Mol Med. 2019; 23(7): 4738-4745.
  20. Zheng R, Liang J, Lu J, Li S, Zhang G, Wang X, et al. Genome-wide long non-coding RNAs identified a panel of novel plasma biomarkers for gastric cancer diagnosis. Gastric Cancer. 2019; 22(4): 731- 741.
  21. Cao W, Liu JN, Liu Z, Wang X, Han ZG, Ji T, et al. A three-lncRNA signature derived from the Atlas of ncRNA in cancer (TANRIC) database predicts the survival of patients with head and neck squamous cell carcinoma. Oral Oncol. 2017; 65: 94-101.
  22. Wang H, Huo X, Yang XR, He J, Cheng L, Wang N, et al. STAT3- mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4. Mol Cancer. 2017; 16(1): 136.
  23. Tian Y, Ma R, Sun Y, Liu H, Zhang H, Sun Y, et al. SP1-activated long noncoding RNA lncRNA GCMA functions as a competing endogenous RNA to promote tumor metastasis by sponging miR-124 and miR-34a in gastric cancer. Oncogene. 2020; 39(25): 4854- 4868.
  24. Wang C, Tan C, Wen Y, Zhang D, Li G, Chang L, et al. FOXP1- induced lncRNA CLRN1-AS1 acts as a tumor suppressor in pituitary prolactinoma by repressing the autophagy via inactivating Wnt/β-catenin signaling pathway. Cell Death Dis. 2019; 10(7): 499.
  25. Tang W, Zhou W, Xiang L, Wu X, Zhang P, Wang J, et al. The p300/ YY1/miR-500a-5p/HDAC2 signalling axis regulates cell proliferation in human colorectal cancer. Nat Commun. 2019; 10(1): 663.
  26. Li K, Ma YB, Tian YH, Xu XL, Gao Y, He YQ, et al. Silencing lncRNA SNHG6 suppresses proliferation and invasion of breast cancer cells through miR-26a/VASP axis. Pathol Res Pract. 2019; 215(10): 152575.
  27. Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competition. Nature. 2014; 505(7483): 344-352.
  28. Qi X, Zhang DH, Wu N, Xiao JH, Wang X, Ma W. ceRNA in cancer: possible functions and clinical implications. J Med Genet. 2015; 52(10): 710-718.
  29. Gu X, Jiang Y, Xue W, Song C, Wang Y, Liu Y, et al. SPNS2 promotes the malignancy of colorectal cancer cells via regulating Akt and ERK pathway. Clin Exp Pharmacol Physiol. 2019; 46(9): 861- 871 .
  30. Bradley E, Dasgupta S, Jiang X, Zhao X, Zhu G, He Q, et al. Critical role of Spns2, a sphingosine-1-phosphate transporter, in lung cancer cell survival and migration. PLoS One. 2014; 9(10): e110119.
  31. Yang R, Xing L, Zheng X, Sun Y, Wang X, Chen J. The circRNA circAGFG1 acts as a sponge of miR-195-5p to promote triplenegative breast cancer progression through regulating CCNE1 expression. Mol Cancer. 2019; 18(1): 4.
  32. Liu S, Wang Z, Liu Z, Shi S, Zhang Z, Zhang J, et al. miR-221/222 activate the Wnt/β-catenin signaling to promote triple-negative breast cancer. J Mol Cell Biol. 2018; 10(4): 302-315.
  33. Chen LL, Zhang ZJ, Yi ZB, Li JJ. MicroRNA-211-5p suppresses tumour cell proliferation, invasion, migration and metastasis in triplenegative breast cancer by directly targeting SETBP1. Br J Cancer. 2017; 117(1): 78-88.
  34. Wu RR, Zhong Q, Liu HF, Liu SB. Role of miR-579-3p in the development of squamous cell lung carcinoma and the regulatory mechanisms. Eur Rev Med Pharmacol Sci. 2019; 23(21): 9464-9470.