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Cellular Oncology

, Volume 42, Issue 2, pp 211–221 | Cite as

SNHG6 is upregulated in primary breast cancers and promotes cell cycle progression in breast cancer-derived cell lines

  • Amin Jafari-Oliayi
  • Malek Hossein AsadiEmail author
Original Paper
  • 115 Downloads

Abstract

Background

Long non-coding RNAs (lncRNAs) are known as RNAs that do not encode proteins and that are more than 200 nucleotides in size. Previously, it has been found that LncRNAs play crucial roles in normal cellular processes, including proliferation and apoptosis. A growing body of evidence suggests that lncRNAs may also play regulatory roles in the initiation, progression and metastasis of various malignancies, including breast cancer. SNHG6 is a lncRNA that has previously been found to contribute to the initiation and progression of hepatocellular and gastric carcinomas. In this study, the clinical significance of SNHG6 expression in breast cancer was investigated.

Methods

SNHG6 expression in primary breast cancer tissues was assessed using RT-qPCR. The functional role of SNHG6 was investigated using RNAi-mediated silencing and exogenous overexpression in breast cancer-derived cells. MTT, colony formation, cell cycle, apoptosis and senescence assays were used to determine the impact of SNHG6 expression on breast cancer-derived cells. The effect of SNHG6 on the migration and epithelial-to-mesenchymal transition (EMT) of breast cancer-derived cells was determined using scratch wound healing and immunofluorescence assays, respectively.

Results

We found that the expression of SNHG6 was significantly upregulated in primary high-grade and progesterone receptor (PR)-positive breast tumours. Additional siRNA-based experiments revealed that SNHG6 silencing led to G1 cell cycle arrest in SK-BR-3 and MDA-MB-231 breast cancer-derived cells. Moreover, we found that SNHG6 silencing led to suppressed breast cancer cell proliferation by inducing apoptosis and senescence. Our data also indicate that SNHG6 may contribute to the migration and EMT of breast cancer cells.

Conclusions

Our results indicate that lncRNA SNHG6 is involved in breast cancer development and may be considered as a potential biomarker for the diagnosis, prognosis and treatment of breast cancer.

Keywords

LncRNA SNHG6 Breast Cancer EMT 

Notes

Acknowledgments

This research was supported by the Iran National Science Foundation (INSF) grant number 93030186. All biological materials were provided by the IRAN NATIONAL TUMOR BANK, which is funded by the Cancer Institute of Tehran University of Medical Sciences for Cancer Research.

Compliance with ethical standards

Conflict of interest

The authors declared that they have no conflicts of interest.

References

  1. 1.
    R.L. Siegel, K.D. Miller, A. Jemal, Cancer statistics, 2017. CA Cancer J. Clin. 67, 7–30 (2017)CrossRefGoogle Scholar
  2. 2.
    P. Samadi, S. Saki, F.K. Dermani, M. Pourjafar, M. Saidijam, Emerging ways to treat breast cancer: Will promises be met? Cell. Oncol. 41, 605–621 (2018)CrossRefGoogle Scholar
  3. 3.
    V. Tripathi, J.D. Ellis, Z. Shen, D.Y. Song, Q. Pan, A.T. Watt, S.M. Freier, C.F. Bennett, A. Sharma, P.A. Bubulya, The nuclear-retained noncoding RNA MALAT1 regulates alternative splicing by modulating SR splicing factor phosphorylation. Mol. Cell 39, 925–938 (2010)CrossRefGoogle Scholar
  4. 4.
    S.Y. Ng, R. Johnson, L.W. Stanton, Human long non-coding RNAs promote pluripotency and neuronal differentiation by association with chromatin modifiers and transcription factors. EMBO J. 31, 522–533 (2012)CrossRefGoogle Scholar
  5. 5.
    J.E. Wilusz, H. Sunwoo, D.L. Spector, Long noncoding RNAs: Functional surprises from the RNA world. Genes Dev. 23, 1494–1504 (2009)CrossRefGoogle Scholar
  6. 6.
    R. Castro-Oropeza, J. Melendez-Zajgla, V. Maldonado, K. Vazquez-Santillan, The emerging role of lncRNAs in the regulation of cancer stem cells. Cell. Oncol. 41, 585–603 (2018)CrossRefGoogle Scholar
  7. 7.
    S.P. Nana-Sinkam, C.M. Croce, Non-coding RNAs in cancer initiation and progression and as novel biomarkers. Mol. Oncol. 5, 483–491 (2011)CrossRefGoogle Scholar
  8. 8.
    F. Calore, F. Lovat, M. Garofalo, Non-coding RNAs and cancer. Int. J. Mol. Sci. 14, 17085–17110 (2013)CrossRefGoogle Scholar
  9. 9.
    M.L. Pecero, J. Salvador-Bofill, S. Molina-Pinelo, Long non-coding RNAs as monitoring tools and therapeutic targets in breast cancer. Cell. Oncol. 42, 1–12 (2019).  https://doi.org/10.1007/s13402-018-0412-6
  10. 10.
    R.H. Fan, J.N. Guo, W. Yan, M.D. Huang, C.L. Zhu, Y.M. Yin, X.F. Chen, mall nucleolar host gene 6 promotes esophageal squamous cell carcinoma cell proliferation and inhibits cell apoptosis. Oncol. Lett. 15, 6497–6502 (2018)Google Scholar
  11. 11.
    A.G. Matera, R.M. Terns, M.P. Terns, Non-coding RNAs: Lessons from the small nuclear and small nucleolar RNAs. Nat. Rev. Mol. Cell Biol. 8, 209–220 (2007)CrossRefGoogle Scholar
  12. 12.
    H. Su, T. Xu, S. Ganapathy, M. Shadfan, M. Long, T.H. Huang, I. Thompson, Z. Yuan, Elevated snoRNA biogenesis is essential in breast cancer. Oncogene 33, 1348–1358 (2014)CrossRefGoogle Scholar
  13. 13.
    L. Chang, Y. Yuan, C. Li, T. Guo, H. Qi, Y. Xiao, X. Dong, Z. Liu, Q. Liu, Upregulation of SNHG6 regulates ZEB1 expression by competitively binding miR-101-3p and interacting with UPF1 in hepatocellular carcinoma. Cancer Lett. 383, 183–194 (2016)CrossRefGoogle Scholar
  14. 14.
    C. Cao, T. Zhang, D. Zhang, L. Xie, X. Zou, L. Lei, D. Wu, L. Liu, The long non-coding RNA, SNHG6-003, functions as a competing endogenous RNA to promote the progression of hepatocellular carcinoma. Oncogene 36, 1112–1122 (2017)CrossRefGoogle Scholar
  15. 15.
    K. Yan, J. Tian, W. Shi, H. Xia, Y. Zhu, LncRNA SNHG6 is associated with poor prognosis of gastric Cancer and promotes cell proliferation and EMT through epigenetically silencing p27 and sponging miR-101-3p. Cell. Physiol. Biochem. 42, 999–1012 (2017)CrossRefGoogle Scholar
  16. 16.
    K. Itahana, Y. Itahana, G.P. Dimri, Colorimetric detection of senescence-associated β galactosidase. Methods Mol. Biol. 956, 143–156 (2013)CrossRefGoogle Scholar
  17. 17.
    H.R. Bardaji, M.H. Asadi, M.M. Yaghoobi, Long noncoding RNA VIM-AS1 promotes colorectal cancer progression and metastasis by inducing EMT. Eur. J. Cell Biol. 97, 279–288 (2018)CrossRefGoogle Scholar
  18. 18.
    F.J. Alipoor, M.H. Asadi, M.T. Mahani, MIAT lncRNA is overexpressed in breast cancer and its inhibition triggers senescence and G1 arrest in MCF7 cell line. J. Cell. Biochem. 119, 6470–6481 (2018)CrossRefGoogle Scholar
  19. 19.
    J.R. Prensner, W. Chen, S. Han, M.K. Iyer, Q. Cao, V. Kothari, J.R. Evans, K.E. Knudsen, M.T. Paulsen, M. Ljungman, T.S. Lawrence, A.M. Chinnaiyan, F.Y. Feng, The long non-coding RNA PCAT-1 promotes prostate cancer cell proliferation through cMyc. Neoplasia 16, 900–908 (2014)CrossRefGoogle Scholar
  20. 20.
    T. Du, B. Zhang, S. Zhang, X. Jiang, P. Zheng, J. Li, M. Yan, Z. Zhu, B. Liu, Decreased expression of long non-coding RNA WT1-AS promotes cell proliferation and invasion in gastric cancer. Biochim. Biophys. Acta 1862, 12–19 (2015)CrossRefGoogle Scholar
  21. 21.
    S. Yang, J. Liu, A.D. Thor, X. Yang, Caspase expression profile and functional activity in a panel of breast cancer cell lines. Oncol. Rep. 17, 1229–1235 (2007)Google Scholar
  22. 22.
    J.P. Alao, The regulation of cyclin D1 degradation: Roles in cancer development and the potential for therapeutic invention. Mol. Cancer 6, 24 (2007)CrossRefGoogle Scholar
  23. 23.
    F. Rodier, J. Campisi, Four faces of cellular senescence. J. Cell Biol. 192, 547–556 (2011)CrossRefGoogle Scholar
  24. 24.
    M. Mumcuoglu, S. Bagislar, H. Yuzugullu, H. Alotaibi, S. Senturk, P. Telkoparan, B. Gur-Dedeoglu, B. Cingoz, B. Bozkurt, U.H. Tazebay, The ability to generate senescent progeny as a mechanism underlying breast cancer cell heterogeneity. PLoS One 5, e11288 (2010)CrossRefGoogle Scholar
  25. 25.
    B.G. Childs, D.J. Baker, J.L. Kirkland, J. Campisi, J.M. Van Deursen, Senescence and apoptosis: Dueling or complementary cell fates? EMBO Rep. 15, 1139–1153 (2014)CrossRefGoogle Scholar
  26. 26.
    B. De Craene, G. Berx, Regulatory networks defining EMT during cancer initiation and progression. Nat. Rev. Cancer 13, 97–110 (2013)CrossRefGoogle Scholar
  27. 27.
    E. Whiteman, C. Liu, E. Fearon, B. Margolis, The transcription factor snail represses Crumbs3 expression and disrupts apico-basal polarity complexes. Oncogene 27, 3875–3879 (2008)CrossRefGoogle Scholar

Copyright information

© International Society for Cellular Oncology 2019

Authors and Affiliations

  1. 1.Department of Biotechnology, Institute of Science and High Technology and Environmental SciencesGraduate University of Advanced TechnologyKermanIran

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