Original Article | Published:

PTENP1 acts as a ceRNA to regulate PTEN by sponging miR-19b and explores the biological role of PTENP1 in breast cancer

Cancer Gene Therapy volume 24, pages 309315 (2017) | Download Citation

Abstract

This study aimed to investigate role of long noncoding RNA PTENP1 regulating PTEN expression via miR-19b to affect breast cancer (BC) progression. We measured expressions of PTENP1, miR-19b and PTEN in 65 matched BC cancerous and noncancerous tissues by quantitative real-time fluorescence PCR (qRT-PCR) and investigated the biological effects of PTENP1 in BC MDA-MB-231 cells by several in vitro experiments including CCK8, wound healing, transwell and Annexin V-FITC/PI analysis. Besides, the competing endogenous RNA (ceRNA) activity of PTENP1 on miR-19b was detected by luciferase reporter assay, and the expressions of related genes and proteins were determined by western blot assay and qRT-PCR. Increased PTENP1 and PTEN and decreased miR-19b were observed in BC tissues and cell lines. Further, PTENP1 and PTEN are direct targets of miR-19b, and overexpressed PTENP1 in MDA-MB-231 cells could supress cell proliferation, migration and invasion and promote cell apoptosis. Moreover, PTENP1 could upregulate PTEN via its ceRNA interaction on miR-19b, as well as induced the upregulation of p53 and downregulation of p-AKT. Enhanced PTENP1 could inhibit BC cell growth, metastasis and tumourigenicity by inhibiting miR-19b and facilitating PTEN in BC, thereby may represent a novel target for diagnosis and treatment of BC.

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References

  1. 1.

    . Understanding breast cancer—The long and winding road. BBA Clin 2017; 7: 64–77.

  2. 2.

    , , . Emerging breast cancer epidemic: evidence from Africa. Breast Cancer Res 2010; 12: S8.

  3. 3.

    , , , , , et al. Thymosin beta 10 is a key regulator of tumorigenesis and metastasis and a novel serum marker in breast cancer. Breast Cancer Res 2017; 19: 15.

  4. 4.

    , , , , , et al. The role of targeted therapy and biomarkers in breast cancer treatment. Clin Exp Metastasis 2012; 29: 807–819.

  5. 5.

    , , . Long noncoding RNAs: past, present, and future. Genetics 2013; 193: 651–669.

  6. 6.

    , , , , , et al. lncRNAs: novel players in intervertebral disc degeneration and osteoarthritis. Cell Prolif 2017; 50.

  7. 7.

    , , , , , et al. The long noncoding RNA PVT1 functions as a competing endogenous RNA by sponging miR-186 in gastric cancer. Biomed Pharmacother 2017; 88: 302–308.

  8. 8.

    , , , , , et al. Human cancer long non-coding RNA transcriptomes. PloS One 2011; 6: e25915.

  9. 9.

    , , , , , et al. H19 lncRNA mediates 17beta-estradiol-induced cell proliferation in MCF-7 breast cancer cells. Oncol Rep 2015; 33: 3045–3052.

  10. 10.

    , , , , , et al. LincRNA-ROR induces epithelial-to-mesenchymal transition and contributes to breast cancer tumorigenesis and metastasis. Cell Death Dis 2014; 5: e1287.

  11. 11.

    , , , , , et al. Long non-coding RNA UCA1 promotes breast tumor growth by suppression of p27 (Kip1). Cell Death Dis 2014; 5: e1008.

  12. 12.

    , . Regulation of apoptosis by long non-coding RNA GAS5 in breast cancer cells: implications for chemotherapy. Breast Cancer Res Treat 2014; 145: 359–370.

  13. 13.

    , , , , , et al. Pseudogene PTENP1 suppresses gastric cancer progression by modulating PTEN. Anticancer Agents Med Chem 2016; 16: 456–464.

  14. 14.

    , , . The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 2012; 13: 283–296.

  15. 15.

    , , , , , et al. Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell 2011; 147: 344–357.

  16. 16.

    , , , , , . Pseudogene PTENP1 functions as a competing endogenous RNA (ceRNA) to regulate PTEN expression by sponging miR-499-5p. Biochemistry 2016; 81: 739–747.

  17. 17.

    , , , , , . A coding-independent function of gene and pseudogene mRNAs regulates tumour biology. Nature 2010; 465: 1033–1038.

  18. 18.

    , , , , , et al. PTENp1, a natural sponge of miR-21, mediates PTEN expression to inhibit the proliferation of oral squamous cell carcinoma. Mol Carcinog 2016; 56: 1322–1334.

  19. 19.

    , , , , , et al. Pseudogene PTENP1 functions as a competing endogenous RNA to suppress clear-cell renal cell carcinoma progression. Mol Cancer Therapeut 2014; 13: 3086–3097.

  20. 20.

    , . Declaration of Helsinki. Med J Aust 1964; 2: 320–321.

  21. 21.

    , , , , , et al. LncSubpathway: a novel approach for identifying dysfunctional subpathways associated with risk lncRNAs by integrating lncRNA and mRNA expression profiles and pathway topologies. Oncotarget 2017; 8: 15453–15469.

  22. 22.

    , , , . Long noncoding RNA MALAT1-regulated microRNA 506 modulates ovarian cancer growth by targeting iASPP. Onco Targets Ther 2017; 10: 35–46.

  23. 23.

    , , , , . Long noncoding RNA highly up-regulated in liver cancer predicts unfavorable outcome and regulates metastasis by MMPs in triple-negative breast cancer. Arch Med Res 2016; 47: 446–453.

  24. 24.

    , , , , , . Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer. PLoS One 2017; 12: e0171661.

  25. 25.

    , , , , , et al. Long non-coding RNA LINC00628 suppresses the growth and metastasis and promotes cell apoptosis in breast cancer. Eur Rev Med Pharmacol Sci 2017; 21: 275–283.

  26. 26.

    , , , , , . Effects of long noncoding RNA-ROR on tamoxifen resistance of breast cancer cells by regulating microRNA-205. Cancer Chemother Pharmacol 2017; 79: 327–337.

  27. 27.

    , , , , . LSINCT5 is over expressed in breast and ovarian cancer and affects cellular proliferation. RNA Biol 2011; 8: 496–505.

  28. 28.

    , , . MEG3 noncoding RNA: a tumor suppressor. J Mol Endocrinol 2012; 48: R45–R53.

  29. 29.

    , , , , , et al. Negative regulation of lncRNA GAS5 by miR-21. Cell Death Differ 2013; 20: 1558–1568.

  30. 30.

    , , , , , et al. miR-19 is a key oncogenic component of mir-17-92. Genes Dev 2009; 23: 2839–2849.

  31. 31.

    , , , , , et al. MiR-19b suppresses PTPRG to promote breast tumorigenesis. Oncotarget 2016; 7: 64100–64108.

  32. 32.

    , , , , , et al. miR-19b attenuates H2O2-induced apoptosis in rat H9C2 cardiomyocytes via targeting PTEN. Oncotarget 2016; 7: 10870–10878.

  33. 33.

    , , , , . Regulation of miR-19 to breast cancer chemoresistance through targeting PTEN. Pharm Res 2011; 28: 3091–3100.

  34. 34.

    , , , , , et al. Long non-coding RNA PTENP1 functions as a ceRNA to modulate PTEN level by decoying miR-106b and miR-93 in gastric cancer. Oncotarget 2017; 8: 26079–26089.

  35. 35.

    , , , . Metformin and rapamycin have distinct effects on the AKT pathway and proliferation in breast cancer cells. Breast Cancer Res Treatment 2010; 123: 271–279.

  36. 36.

    , , , , . Tetramer formation of tumor suppressor protein p53: Structure, function, and applications. Biopolymers 2016; 106: 598–612.

  37. 37.

    , , , , , et al. Negative regulation of the tumor suppressor p53 gene by microRNAs. Oncogene 2011; 30: 843–853.

  38. 38.

    , , , , , et al. Curcumin modulates miR-19/PTEN/AKT/p53 axis to suppress bisphenol A-induced MCF-7 breast cancer cell proliferation. Phytother Res 2014; 28: 1553–1560.

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Acknowledgements

We appreciate the reviewers for their useful comments in this paper.

Author information

Affiliations

  1. Department of Clinical Laboratory, Shantou University Medical College, Shantou, Guangdong, China

    • R-K Li
    •  & W-H Luo
  2. Department of Clinical Laboratory, The Second People’s Hospital of Baoan District of Shenzhen, Shenzhen, Guangdong, China

    • R-K Li
    •  & J- Gao
  3. Department of Clinical Laboratory, People’s Hospital of New District Longhua, Shenzhen, Guangdong, China

    • L-H Guo
    •  & G-Q Huang

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Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to W-H Luo.

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DOI

https://doi.org/10.1038/cgt.2017.29

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