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Non-Coding RNA Pvt1 Promotes Cancer Stem Cell–Like Traits in Nasopharyngeal Cancer via Inhibiting miR-1207

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Pathology & Oncology Research

Abstract

Nasopharyngeal carcinoma (NPC) is a kind of head-neck malignant tumor. lncRNA-PVT1 can promote the proliferation of carcinoma cells, and induce cells to have stem cell-like potentials. However, the function of PVT1 in NPC cells is not clear. The expressions of lncRNA-PVT1 and the expressions of the stem cell markers in NPC tissues or cell lines were investigated by qRT-PCR or western blot. The cell proliferation, and the ability of NPC cells to form spherical, clonal colonies were investigated by MTT assay, colony formation assay, and tumor-sphere formation assay. Cancer stem cells surface markers were detected by flow cytometry and western blot. PI3K/AKT signal activation in NPC cells was determined by western blot. PVT1 was significantly up-regulated in both NPC tissues and cell lines and associated with poor prognosis. PVT1 knockdown reduced NPC cells viability, clonogenicity, the cell surface CD44+/CD24− stem phenotype, and the expressions of the stem cell markers in NPC cells, including Oct4, c-Myc, SOX2, and ALDH. Furthermore, PVT1 negatively regulates the expression levels of miR-1207 in NPC cells and spheres cells, which is critical for NPC stemness. Knockdown of miR-1207 promoted stem phenotype and the expressions of the stem cell markers in NPC cells. Moreover, phosphor-PI3K (p-PI3K) and phosphor-AKT (p-AKT) were found to be down-regulated after PVT1 siRNAs transfection in NPC cells. And miR-1207 inhibitor transfection reversed the all the effects brought by PVT1 knockdown. Pvt1 promotes cancer stem cell–like properties in NPC cells via inhibiting miR-1207 and activating the PI3K/AKT signal pathway.

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Fig. 1: PVT1 is up-regulated in both NPC tissues and cell lines and associated with poor prognosis.
Fig. 2: Knockdown of PVT1 suppresses the proliferation and clonogenicity of NPC cells.
Fig. 3: Knockdown of PVT1 attenuates cancer stem cell-like properties in NPC cells.
Fig. 4: PVT1 negatively regulates the expression of miR-1204 and 1207 in NPC cells.
Fig. 5: MiR-1207 inhibits the NPC cell proliferation and stem cell-like properties.
Fig. 6: Knockdown of PVT1 inhibits PI3K/AKT signal pathway.

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References

  1. Chou J et al (2008) Nasopharyngeal carcinoma--review of the molecular mechanisms of tumorigenesis. Head Neck 30(7):946–963

    PubMed  PubMed Central  Google Scholar 

  2. Xu T et al (2013) Recurrent nasopharyngeal carcinoma: a clinical dilemma and challenge. Curr Oncol 20(5):e406–e419

    PubMed  PubMed Central  Google Scholar 

  3. Albini A et al (2015) Cancer stem cells and the tumor microenvironment: interplay in tumor heterogeneity. Connect Tissue Res 56(5):414–425

    PubMed  PubMed Central  Google Scholar 

  4. Baccelli I, Trumpp A (2012) The evolving concept of cancer and metastasis stem cells. J Cell Biol 198(3):281–293

    CAS  PubMed  PubMed Central  Google Scholar 

  5. Visvader JE, Lindeman GJ (2008) Cancer stem cells in solid tumours: accumulating evidence and unresolved questions. Nat Rev Cancer 8(10):755–768

    CAS  PubMed  Google Scholar 

  6. Han Y et al (2015) Advanced applications of RNA sequencing and challenges. Bioinform Biol Insights 9(Suppl 1):29–46

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Cech TR, Steitz JA (2014) The noncoding RNA revolution-trashing old rules to forge new ones. Cell 157(1):77–94

    CAS  PubMed  Google Scholar 

  8. Huang T et al (2013) Noncoding RNAs in cancer and cancer stem cells. Chin J Cancer 32(11):582–593

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Huarte M (2015) The emerging role of lncRNAs in cancer. Nat Med 21(11):1253–1261

    CAS  PubMed  Google Scholar 

  10. Schmitt AM, Chang HY (2016) Long noncoding RNAs in Cancer pathways. Cancer Cell 29(4):452–463

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Wang Y et al (2015) A novel long non-coding RNA, hypoxia-inducible factor-2alpha promoter upstream transcript, functions as an inhibitor of osteosarcoma stem cells in vitro. Mol Med Rep 11(4):2534–2540

    CAS  PubMed  Google Scholar 

  12. Zhou M et al (2016) LncRNA-Hh strengthen Cancer stem cells generation in twist-positive breast Cancer via activation of hedgehog signaling pathway. Stem Cells 34(1):55–66

    CAS  PubMed  Google Scholar 

  13. Colombo T et al (2015) PVT1: a rising star among oncogenic long noncoding RNAs. Biomed Res Int 2015:304208

    PubMed  PubMed Central  Google Scholar 

  14. Graham M, Adams JM (1986) Chromosome 8 breakpoint far 3′ of the c-myc oncogene in a Burkitt's lymphoma 2;8 variant translocation is equivalent to the murine pvt-1 locus. EMBO J 5(11):2845–2851

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Iaccarino I (2017) lncRNAs and MYC: An Intricate Relationship. Int J Mol Sci 18(7):1497

    PubMed Central  Google Scholar 

  16. Tseng YY et al (2014) PVT1 dependence in cancer with MYC copy-number increase. Nature 512(7512):82–86

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Huppi K et al (2008) The identification of microRNAs in a genomically unstable region of human chromosome 8q24. Mol Cancer Res 6(2):212–221

    CAS  PubMed  Google Scholar 

  18. Cui M et al (2016) Long non-coding RNA PVT1 and cancer. Biochem Biophys Res Commun 471(1):10–14

    CAS  PubMed  Google Scholar 

  19. Conte F et al (2017) Role of the long non-coding RNA PVT1 in the dysregulation of the ceRNA-ceRNA network in human breast cancer. PLoS One 12(2):e0171661

    PubMed  PubMed Central  Google Scholar 

  20. Cui D et al (2016) Long non-coding RNA PVT1 as a novel biomarker for diagnosis and prognosis of non-small cell lung cancer. Tumour Biol 37(3):4127–4134

    CAS  PubMed  Google Scholar 

  21. Ding J et al (2014) Expression and clinical significance of the long non-coding RNA PVT1 in human gastric cancer. Onco Targets Ther 7:1625–1630

    PubMed  PubMed Central  Google Scholar 

  22. Gao YL et al (2017) Long non-coding RNA PVT1 facilitates cervical Cancer progression via negative regulating of miR-424. Oncol Res 25:1391–1398

    PubMed  PubMed Central  Google Scholar 

  23. Guo K et al (2017) The expression pattern of long non-coding RNA PVT1 in tumor tissues and in extracellular vesicles of colorectal cancer correlates with cancer progression. Tumour Biol 39(4):1010428317699122

    PubMed  Google Scholar 

  24. Liu E et al (2015) Overexpression of long non-coding RNA PVT1 in ovarian cancer cells promotes cisplatin resistance by regulating apoptotic pathways. Int J Clin Exp Med 8(11):20565–20572

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Zhang XW et al (2015) Overexpression of long non-coding RNA PVT1 in gastric cancer cells promotes the development of multidrug resistance. Biochem Biophys Res Commun 462(3):227–232

    CAS  PubMed  Google Scholar 

  26. Zhuang C et al (2015) Tetracycline-inducible shRNA targeting long non-coding RNA PVT1 inhibits cell growth and induces apoptosis in bladder cancer cells. Oncotarget 6(38):41194–41203

    PubMed  PubMed Central  Google Scholar 

  27. Wang F et al (2014) Oncofetal long noncoding RNA PVT1 promotes proliferation and stem cell-like property of hepatocellular carcinoma cells by stabilizing NOP2. Hepatology 60(4):1278–1290

    CAS  PubMed  Google Scholar 

  28. Alvarez ML et al (2013) Role of microRNA 1207-5P and its host gene, the long non-coding RNA Pvt1, as mediators of extracellular matrix accumulation in the kidney: implications for diabetic nephropathy. PLoS One 8(10):e77468

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Marur S, Forastiere AA (2016) Head and neck squamous cell carcinoma: update on epidemiology, diagnosis, and treatment. Mayo Clin Proc 91(3):386–396

    PubMed  Google Scholar 

  30. Hu S, Shan G (2016) LncRNAs in Stem Cells. Stem Cells Int 2016:2681925

    PubMed  PubMed Central  Google Scholar 

  31. Rosa A, Ballarino M (2016) Long noncoding RNA regulation of pluripotency. Stem Cells Int 2016:1797692

    PubMed  Google Scholar 

  32. Wang Y et al (2013) Endogenous miRNA sponge lincRNA-RoR regulates Oct4, Nanog, and Sox2 in human embryonic stem cell self-renewal. Dev Cell 25(1):69–80

    CAS  PubMed  Google Scholar 

  33. Yang YR et al (2014) Increased expression of the lncRNA PVT1 promotes tumorigenesis in non-small cell lung cancer. Int J Clin Exp Pathol 7(10):6929–6935

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Franca GS, Vibranovski MD, Galante PA (2016) Host gene constraints and genomic context impact the expression and evolution of human microRNAs. Nat Commun 7:11438

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Barsotti AM et al (2012) p53-dependent induction of PVT1 and miR-1204. J Biol Chem 287(4):2509–2519

    CAS  PubMed  Google Scholar 

  36. Riquelme E et al (2014) Frequent coamplification and cooperation between C-MYC and PVT1 oncogenes promote malignant pleural mesothelioma. J Thorac Oncol 9(7):998–1007

    PubMed  PubMed Central  Google Scholar 

  37. Chen L et al (2014) miR-1207-5p and miR-1266 suppress gastric cancer growth and invasion by targeting telomerase reverse transcriptase. Cell Death Dis 5:e1034

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Zhang S, Cui W (2014) Sox2, a key factor in the regulation of pluripotency and neural differentiation. World J Stem Cells 6(3):305–311

    PubMed  PubMed Central  Google Scholar 

  39. Rizzino A (2013) Concise review: the Sox2-Oct4 connection: critical players in a much larger interdependent network integrated at multiple levels. Stem Cells 31(6):1033–1039

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Hadjimichael C et al (2015) Common stemness regulators of embryonic and cancer stem cells. World J Stem Cells 7(9):1150–1184

    PubMed  PubMed Central  Google Scholar 

  41. Leis O et al (2012) Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene 31(11):1354–1365

    CAS  PubMed  Google Scholar 

  42. Ginestier C et al (2007) ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1(5):555–567

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Xia P, Xu XY (2015) PI3K/Akt/mTOR signaling pathway in cancer stem cells: from basic research to clinical application. Am J Cancer Res 5(5):1602–1609

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Sunayama J et al (2010) Crosstalk between the PI3K/mTOR and MEK/ERK pathways involved in the maintenance of self-renewal and tumorigenicity of glioblastoma stem-like cells. Stem Cells 28(11):1930–1939

    CAS  PubMed  Google Scholar 

  45. Ruggeri BA et al (1998) Amplification and overexpression of the AKT2 oncogene in a subset of human pancreatic ductal adenocarcinomas. Mol Carcinog 21(2):81–86

    CAS  PubMed  Google Scholar 

  46. Wen W et al (2013) Cyclin G1 expands liver tumor-initiating cells by Sox2 induction via Akt/mTOR signaling. Mol Cancer Ther 12(9):1796–1804

    CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to give our sincere gratitude to the reviewers for their constructive comments.

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Authors and Affiliations

  1. Department of Head & Neck and Thyroid, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, People’s Republic of China

    Meng Cui, Qi-Gen Fang, Wei Du, Jun-Fu Wu, Ji-Heng Wang & Shan-Ting Liu

  2. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450008, People’s Republic of China

    Yu Chang

  3. Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, 450008, People’s Republic of China

    Su-Xia Luo

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  1. Meng Cui
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  2. Yu Chang
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  3. Qi-Gen Fang
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  4. Wei Du
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  6. Ji-Heng Wang
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Correspondence to Su-Xia Luo.

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Meng Cui and Yu Chang are co-first authors.

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Cui, M., Chang, Y., Fang, QG. et al. Non-Coding RNA Pvt1 Promotes Cancer Stem Cell–Like Traits in Nasopharyngeal Cancer via Inhibiting miR-1207. Pathol. Oncol. Res. 25, 1411–1422 (2019). https://doi.org/10.1007/s12253-018-0453-1

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  • DOI: https://doi.org/10.1007/s12253-018-0453-1

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