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http://dx.doi.org/10.7314/APJCP.2015.16.11.4509

miR-9 Modulates Osteosarcoma Cell Growth by Targeting the GCIP Tumor Suppressor  

Zhu, Shao-Wen (Tianjin Medical University)
Li, Jian-Peng (Department of Orthopedics, the Fifth Center Hospital of Tianjin)
Ma, Xin-Long (Department of Orthopedics, Tianjin Hospital)
Ma, Jian-Xiong (Department of Orthopedics, Tianjin Hospital)
Yang, Yang (Department of Orthopedics, Tianjin Hospital)
Chen, Yang (Department of Orthopedics, Tianjin Hospital)
Liu, Wei (Tianjin Medical University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.16, no.11, 2015 , pp. 4509-4513 More about this Journal
Abstract
Osteosarcoma is the most common primary bone tumor in humans, especially in childhood. However, the genetic etiology for its pathogenesis remains elusive. It is known that microRNAs (miRNAs) are involved in the development of tumor progression. Here we show that microRNA-9 (miR-9) is a potential oncogene upregulated in osteosarcoma cells. Knockdown of miR-9 in osteosarcoma resulted in suppressed colony formation and cell proliferation. Further study identified GCIP, a Grap2 and cyclin D interacting protein, as a direct target of miR-9. In addition, GCIP overexpression activated retinoblastoma 1 (Rb) and suppressed E2F transcriptional target expression in osteosarcoma cells. Moreover, GCIP depletion reversed miR-9 knockdown induced colony formation and cell proliferation suppression. In sum, these results highlight the importance of miR-9 as an oncogene in regulating the proliferation of osteosarcoma by directly targeting GCIP and may provide new insights into the pathogenesis of osteosarcoma.
Keywords
miR-9; osteosarcoma; GCIP; proliferation; GCIP; tumor suppressor;
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1 Bazzoni F, Rossato M, Fabbri M, et al (2009). Induction and regulatory function of miR-9 in human monocytes and neutrophils exposed to proinflammatory signals. Proc Natl Acad Sci USA, 106, 5282-7.
2 Calin GA, Croce CM (2006). MicroRNA signatures in human cancers. Nature Rev Cancer, 6, 857-66.   DOI
3 Chang TW, Chen CC, Chen KY, et al (2008). Ribosomal phosphoprotein P0 interacts with GCIP and overexpression of P0 is associated with cellular proliferation in breast and liver carcinoma cells. Oncogene, 27, 332-8.   DOI
4 Chen KY, Chen CC, Tseng YL, et al (2014). GCIP functions as a tumor suppressor in non-small cell lung cancer by suppressing Id1-mediated tumor promotion. Oncotarget, 5, 5017-28.   DOI
5 Chen WC, Su PF, Jin YT, et al (2008). Immunohistochemical expression of GCIP in breast carcinoma: relationship with tumour grade, disease-free survival, mucinous differentiation and response to chemotherapy. Histopathol, 53, 554-60.   DOI
6 Delaloy C, Liu L, Lee JA, et al (2010). MicroRNA-9 coordinates proliferation and migration of human embryonic stem cellderived neural progenitors. Cell Stem Cell, 6, 323-35.   DOI
7 Li CJ, Cong Y, Liu XZ, et al (2014). Research progress on the livin gene and osteosarcomas. Asian Pac J Cancer Prev, 15, 8577-9.   DOI
8 Lv H, Guo J, Li S, et al (2014). inhibitor reduces the proliferation and migration in osteosarcoma MG-63 cells. Exp Ther Med, 8, 1575-80.   DOI
9 Ma L, Young J, Prabhala H, et al (2010). miR-9, a MYC/MYCNactivated microRNA, regulates E-cadherin and cancer metastasis. Nat Cell Biol, 12, 247-56.
10 Ma W, Xia X, Stafford LJ, et al (2006). Expression of GCIP in transgenic mice decreases susceptibility to chemical hepatocarcinogenesis. Oncogene, 25, 4207-16.   DOI
11 Moore DD, Luu HH (2014). Osteosarcoma. Cancer Treat Res, 162, 65-92.   DOI
12 Mutsaers AJ, Walkley CR (2014). Cells of origin in osteosarcoma: mesenchymal stem cells or osteoblast committed cells? Bone, 62, 56-63.   DOI
13 Song B, Wang Y, Titmus MA, et al (2010). Molecular mechanism of chemoresistance by miR-215 in osteosarcoma and colon cancer cells. Mol Cancer, 9, 96.   DOI
14 Visani M, de Biase D, Marucci G, et al (2014). Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III. Mol Oncol, 8, 417-30.   DOI
15 Xia C, Bao Z, Tabassam F, et al (2000). GCIP, a novel human grap2 and cyclin D interacting protein, regulates E2F-mediated transcriptional activity. J Biol Chem, 275, 20942-8.   DOI
16 Zhao H, Li M, Li L, et al (2013). MiR-133b Is down-regulated in human osteosarcoma and inhibits osteosarcoma cells proliferation, migration and invasion, and promotes apoptosis. PLoS ONE, 8, 83571.   DOI
17 Ha M, Kim VN (2014). Regulation of microRNA biogenesis. Nature Rev Molecular Cell Biol, 15, 509-24.   DOI
18 Dorfman HD, Czerniak B (1995). Bone cancers. Cancer, 75, 203-10.   DOI
19 Gao F, Zhao ZL, Zhao WT, et al (2013). miR-9 modulates the expression of interferon-regulated genes and MHC class I molecules in human nasopharyngeal carcinoma cells. Biochem Biophys Res Commun, 431, 610-6.   DOI   ScienceOn
20 Gao Y, Luo LH, Li S, et al (2014). miR-17 inhibitor suppressed osteosarcoma tumor growth and metastasis via increasing PTEN expression. Biochem Biophys Res Commun, 444, 230-4.   DOI
21 He JP, Hao Y, Wang XL, et al (2014). Review of the molecular pathogenesis of osteosarcoma. Asian Pac J Cancer Prev, 15, 5967-76.   DOI
22 Hildebrandt MA, Gu J, Lin J, et al (2010). Hsa-miR-9 methylation status is associated with cancer development and metastatic recurrence in patients with clear cell renal cell carcinoma. Oncogene, 29, 5724-8.   DOI
23 Jansson MD, Lund AH (2012). MicroRNA and cancer. Mol Oncol, 6, 590-610.   DOI
24 John B, Enright AJ, Aravin A, et al (2004). Human microRNA targets. Plos Biology, 2, 1862-79.
25 Kavitha N, Vijayarathna S, Jothy SL, et al (2014). MicroRNAs: biogenesis, roles for carcinogenesis and as potential biomarkers for cancer diagnosis and prognosis. Asian Pac J Cancer Prev, 15, 7489-97.   DOI
26 Lee I, Yeom SY, Lee SJ, et al (2010). A novel senescence-evasion mechanism involving Grap2 and cyclin D interacting protein inactivation by ras associated with diabetes in cancer cells under doxorubicin treatment. Cancer Res, 70, 4357-65.   DOI
27 Zhuang G, Wu X, Jiang Z, et al (2012). Tumour-secreted miR-9 promotes endothelial cell migration and angiogenesis by activating the JAK-STAT pathway. EMBO J, 31, 3513-23.   DOI
28 Zhao SF, Zhang X, Zhang XJ, et al (2014). Induction of microRNA-9 mediates cytotoxicity of curcumin against SKOV3 ovarian cancer cells. Asian Pac J Cancer Prev, 15, 3363-8.   DOI