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The tumor suppressor role of PAQR3 in osteosarcoma

  • Research Article
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Tumor Biology

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.

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References

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  PubMed Central  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Yang J, Zhang W. New molecular insights into osteosarcoma targeted therapy. Curr Opin Oncol. 2013;25:398–406.

    Article  CAS  PubMed  Google Scholar 

  5. Cai H, Lin L, Tang M, Wang Z. Prognostic evaluation of microrna-210 expression in pediatric osteosarcoma. Med Oncol. 2013;30:499.

    Article  PubMed  Google Scholar 

  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.

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Volodko N, Gordon M, Salla M, Ghazaleh HA, Baksh S: Rassf tumor suppressor gene family: Biological functions and regulation. FEBS Lett. 2014.

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

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

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Authors and Affiliations

  1. Department of Orthopedic Surgery, The Second Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, People’s Republic of China

    Zhiqiang Ma, Yanlong Wang, Zhaopeng Li, Hongyu Zhang, Zhixin Liu & Jianyu Liu

  2. Children’s Hospital of Harbin, Harbin, Heilongjiang Province, 150010, People’s Republic of China

    Taikui Piao

Authors
  1. Zhiqiang Ma
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  2. Yanlong Wang
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  3. Taikui Piao
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  4. Zhaopeng Li
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  5. Hongyu Zhang
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  6. Zhixin Liu
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  7. Jianyu Liu
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Correspondence to Jianyu Liu.

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Ma, Z., Wang, Y., Piao, T. et al. The tumor suppressor role of PAQR3 in osteosarcoma. Tumor Biol. 36, 3319–3324 (2015). https://doi.org/10.1007/s13277-014-2964-z

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  • DOI: https://doi.org/10.1007/s13277-014-2964-z

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