Tumor Biology

, Volume 36, Issue 5, pp 3319–3324 | Cite as

The tumor suppressor role of PAQR3 in osteosarcoma

  • Zhiqiang Ma
  • Yanlong Wang
  • Taikui Piao
  • Zhaopeng Li
  • Hongyu Zhang
  • Zhixin Liu
  • Jianyu Liu
Research Article

Abstract

Osteosarcoma is the most common primary bone malignancy; however, the molecular mechanisms of development are not well understood. Progestin and AdipoQ receptors (PAQR3), a protein specifically localized in the Golgi apparatus, was recently characterized as a new tumor suppressor. Little is known about the expression and function of PAQR3 in osteosarcoma. Here, we showed that PAQR3 was downregulated in osteosarcoma tissues compared with the adjacent normal regions in 80 paired samples. Moreover, lower levels of PAQR3 were associated with metastasis in clinical osteosarcoma patients. In addition, overexpression of PAQR3 in the osteosarcoma cell line MG-63 inhibited cell proliferation, migration, and invasion by promoting ERK phosphorylation. Taken together, our results indicated that PAQR3 might act as a tumor suppressor in osteosarcoma, providing a novel diagnostic and therapeutic option for human osteosarcoma in the future.

Keywords

Osteosarcoma Tumor suppressor PAQR3 ERK1/2 

Notes

Acknowledgments

This research project was supported by the National Natural Science Foundation of China grant No. 81272015 and Heilongjiang Postdoctoral Fund No. LBH-Z12189.

Conflicts of interest

None

Supplementary material

13277_2014_2964_MOESM1_ESM.doc (43 kb)
ESM 1 (DOC 43 kb)

References

  1. 1.
    Rainusso N, Wang LL, Yustein JT. The adolescent and young adult with cancer: State of the art bone tumors. Curr Oncol Rep. 2013;15:296–307.CrossRefPubMedGoogle Scholar
  2. 2.
    Namlos HM, Meza-Zepeda LA, Baroy T, Ostensen IH, Kresse SH, Kuijjer ML, et al. Modulation of the osteosarcoma expression phenotype by micrornas. PLoS One. 2012;7:e48086.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Zhao H, Guo M, Zhao G, Ma Q, Ma B, Qiu X, et al. Mir-183 inhibits the metastasis of osteosarcoma via downregulation of the expression of ezrin in f5m2 cells. Int J Mol Med. 2012;30:1013–20.PubMedPubMedCentralGoogle Scholar
  4. 4.
    Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406.CrossRefPubMedGoogle Scholar
  5. 5.
    Cai H, Lin L, Tang M, Wang Z. Prognostic evaluation of microrna-210 expression in pediatric osteosarcoma. Med Oncol. 2013;30:499.CrossRefPubMedGoogle Scholar
  6. 6.
    Chung JY, Kim JD, Park GH, Jung ST, Lee KB: Occipito-cervical reconstruction through direct lateral and posterior approach or the treatment of primary osteosarcoma in the atlas: a case report. Spine. 2011.Google Scholar
  7. 7.
    Liang W, Gao B, Fu P, Xu S, Qian Y, Fu Q. The mirnas in the pathogenesis of osteosarcoma. Front Biosci (Landmark Ed). 2013;18:788–94.CrossRefGoogle Scholar
  8. 8.
    He C, Xiong J, Xu X, Lu W, Liu L, Xiao D, et al. Functional elucidation of mir-34 in osteosarcoma cells and primary tumor samples. Biochem Biophys Res Commun. 2009;388:35–40.CrossRefPubMedGoogle Scholar
  9. 9.
    Cai CK, Zhao GY, Tian LY, Liu L, Yan K, Ma YL, et al. Mir-15a and mir-16-1 downregulate ccnd1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncol Rep. 2012;28:1764–70.PubMedGoogle Scholar
  10. 10.
    Zhu J, Feng Y, Ke Z, Yang Z, Zhou J, Huang X, et al. Down-regulation of mir-183 promotes migration and invasion of osteosarcoma by targeting ezrin. Am J Pathol. 2012;180:2440–51.CrossRefPubMedGoogle Scholar
  11. 11.
    Kelly AD, Haibe-Kains B, Janeway KA, Hill KE, Howe E, Goldsmith J, et al. Microrna paraffin-based studies in osteosarcoma reveal reproducible independent prognostic profiles at 14q32. Genome Med. 2013;5:2.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Osaki M, Takeshita F, Sugimoto Y, Kosaka N, Yamamoto Y, Yoshioka Y, et al. Microrna-143 regulates human osteosarcoma metastasis by regulating matrix metalloprotease-13 expression. Mol Ther : J Am Soc Gene Ther. 2011;19:1123–30.CrossRefGoogle Scholar
  13. 13.
    Zhou X, Wei M, Wang W. Microrna-340 suppresses osteosarcoma tumor growth and metastasis by directly targeting rock1. Biochem Biophys Res Commun. 2013;437:653–8.CrossRefPubMedGoogle Scholar
  14. 14.
    Yan K, Gao J, Yang T, Ma Q, Qiu X, Fan Q, et al. Microrna-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS One. 2012;7:e33778.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Fan L, Wu Q, Xing X, Wei Y, Shao Z. Microrna-145 targets vascular endothelial growth factor and inhibits invasion and metastasis of osteosarcoma cells. Acta Biochim Biophys Sin. 2012;44:407–14.CrossRefPubMedGoogle Scholar
  16. 16.
    Wang L, Wang X, Li Z, Xia T, Zhu L, Liu B, et al. Paqr3 has modulatory roles in obesity, energy metabolism, and leptin signaling. Endocrinology. 2013;154:4525–35.CrossRefPubMedGoogle Scholar
  17. 17.
    Wang X, Wang L, Zhu L, Pan Y, Xiao F, Liu W, et al. Paqr3 modulates insulin signaling by shunting phosphoinositide 3-kinase p110alpha to the golgi apparatus. Diabetes. 2013;62:444–56.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Zhang Y, Jiang X, Qin X, Ye D, Yi Z, Liu M, et al. Rktg inhibits angiogenesis by suppressing mapk-mediated autocrine vegf signaling and is downregulated in clear-cell renal cell carcinoma. Oncogene. 2010;29:5404–15.CrossRefPubMedGoogle Scholar
  19. 19.
    Wang X, Li X, Fan F, Jiao S, Wang L, Zhu L, et al. Paqr3 plays a suppressive role in the tumorigenesis of colorectal cancers. Carcinogenesis. 2012;33:2228–35.CrossRefPubMedGoogle Scholar
  20. 20.
    Ling ZQ, Guo W, Lu XX, Zhu X, Hong LL, Wang Z, et al. A golgi-specific protein paqr3 is closely associated with the progression, metastasis and prognosis of human gastric cancers. Ann Oncol: Off J Eur Soc Med Oncol / ESMO. 2014;25:1363–72.CrossRefGoogle Scholar
  21. 21.
    Wu HG, Zhang WJ, Ding Q, Peng G, Zou ZW, Liu T, et al. Identification of paqr3 as a new candidate tumor suppressor in hepatocellular carcinoma. Oncol Rep. 2014;32:2687–95.PubMedGoogle Scholar
  22. 22.
    Saldana-Meyer R, Recillas-Targa F. Transcriptional and epigenetic regulation of the p53 tumor suppressor gene. Epigenetics : Off J DNA Methylation Soc. 2011;6:1068–77.CrossRefGoogle Scholar
  23. 23.
    Lee SH, Ju SK, Lee TY, Huh SH, Han KH. Tip30 directly binds p53 tumor suppressor protein in vitro. Mol Cells. 2012;34:495–500.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Volodko N, Gordon M, Salla M, Ghazaleh HA, Baksh S: Rassf tumor suppressor gene family: Biological functions and regulation. FEBS Lett. 2014.Google Scholar
  25. 25.
    Tsuruta T, Kozaki K, Uesugi A, Furuta M, Hirasawa A, Imoto I, et al. Mir-152 is a tumor suppressor microrna that is silenced by DNA hypermethylation in endometrial cancer. Cancer Res. 2011;71:6450–62.CrossRefPubMedGoogle Scholar
  26. 26.
    Zhang Y, Cai X, Schlegelberger B, Zheng S. Assignment1 of human putative tumor suppressor genes st13 (alias snc6) and st14 (alias snc19) to human chromosome bands 22q13 and 11q24– > q25 by in situ hybridization. Cytogenet Cell Genet. 1998;83:56–7.CrossRefPubMedGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Zhiqiang Ma
    • 1
  • Yanlong Wang
    • 1
  • Taikui Piao
    • 2
  • Zhaopeng Li
    • 1
  • Hongyu Zhang
    • 1
  • Zhixin Liu
    • 1
  • Jianyu Liu
    • 1
  1. 1.Department of Orthopedic SurgeryThe Second Hospital of Harbin Medical UniversityHarbinPeople’s Republic of China
  2. 2.Children’s Hospital of HarbinHarbinPeople’s Republic of China

Personalised recommendations