Abstract
Despite the progress in therapeutic targets, it remains dissatisfactory for most osteosarcoma patients with metastasis or recurrence osteosarcoma. Therefore, it is required to determine the involved mechanisms of osteosarcoma. The aim of this study was to investigate the expression level of MiR-217 and miR-646 and also their association with clinicopathological features in patients with osteosarcoma. Total RNA was purified from patients with osteosarcoma and noncancerous bone tissues, and then quantitative real-time PCR was applied to evaluate the expression level of microRNAs. Our result suggested that miR-217 expression was remarkably deceased in osteosarcoma bone tissue when compared with noncancerous bone tissues (mean ± SD 5.32 ± 1.231, 2.01 ± 0.78; P = 0.024) and miR-646 expression decreased in osteosarcoma bone tissue in comparison with normal tissues (mean ± SD 4.56 ± 1.45, 1.76 ± 1.24; P = 0.041). Our findings indicated that decreased expression of MiR-217 and miR-646 was strongly correlated with high tumor, node, and metastasis (TNM) stage (P = 0.015, P = 0.002) and large cancer diameter (P = 0.041, P = 0.053). Kaplan-Meier survival and log-rank analysis indicated that shorter overall survival was strongly linked to decreased expression of miR-217 and miR-646 (log-rank test P = 0.034, P = 0.026). In terms of miR-217, multivariate Cox proportional hazards model analysis has showed that reduction of miR-217 expression (P = 0.001), TNM stage (P = 0.046), and lymph node metastasis (P = 0.006) were independently linked to a short-time survival of patients. In terms of miR-646, low expression of miR-646 (P = 0.021), TNM stage (P = 0.052), and tumor size (P = 0.043) were independently associated with poor survival of patients as prognostic factors. Our findings suggested that downregulation of MiR-217 and miR-646 was associated with progression of osteosarcoma. MiR-217 and miR-646 may play a key role in suppression of tumor in osteosarcoma and would be applied as a novel therapeutic agent.
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References
Mirabello L, Troisi RJ, Savage SA. Osteosarcoma incidence and survival rates from 1973 to 2004: data from the Surveillance, Epidemiology, and End Results Program. Cancer. 2009;115:1531–43.
Ottaviani G, Jaffe N. The epidemiology of osteosarcoma. Cancer Treat Res. 2009;152:3–13.
Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.
Kuehbacher A, Urbich C, Zeiher AM, Dimmeler S. Role of Dicer and Droshafor endothelial microRNA expression and angiogenesis. Circ Res. 2007;101:59–68.
Finnerty JR, Wang WX, Hébert SS. The miR-15/107 group of microRNA genes: evolutionary biology, cellular functions, and roles in human diseases. J Mol Biol. 2010;402(3):491–509.
Zheng B, Liang L, Wang C, Huang S, Cao X, Zha R, et al. MicroRNA-148a suppresses tumor cell invasion and metastasis by downregulating ROCK1 in gastric cancer. Clin Cancer Res. 2011;17(24):7574–83.
Wu X, Zhong D, Gao Q, Zhai W, Ding Z, Wu J. MicroRNA-34a inhibits human osteosarcoma proliferation by downregulating ether a go-go 1 expression. Int J Med Sci. 2013;10:676–82.
Ueda T, Volinia S, Okumura H, Shimizu M, Taccioli C, Rossi S, et al. Relation between microRNA expression and progression and prognosis of gastric cancer: a microRNA expression analysis. Lancet Oncol. 2010;11:136–46.
Bao YP, Yi Y, Peng LL, Fang J, Liu KB, Li WZ. Roles of microRNA-206 in osteosarcoma pathogenesis and progression. Asian Pac J Cancer Prev. 2013;14:3751–5.
Tang M, Lin L, Cai H, Tang J, Zhou Z. MicroRNA-145 downregulation associates with advanced tumor progression and poor prognosis in patients suffering osteosarcoma. Onco Targets Ther. 2013;6:833–8.
Zhao G, Cai C, Yang T. MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma. PLoS One. 2013;8(1), e53906.
Huang J, Gao K, Lin J. MicroRNA-100 inhibits osteosarcoma cell proliferation by targeting Cyr61. Tumor Biol. 2014;35(2):1095–100.
Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.
Cimino D, De Pitta C, Orso F, Zampini M, Casara S, Penna E, et al. MiR148b is a major coordinator of breast cancer progression in a relapse associated microRNA signature by targeting ITGA5, ROCK1, PIK3CA, NRAS, and CSF1. FASEB J. 2013;27:1223–35.
Zhao WG, Yu SN, Lu ZH, Ma YH, Gu YM, Chen J. The miR-217 microRNA functions as a potential tumor suppressor in pancreatic ductal adenocarcinoma by targeting KRAS. Carcinogenesis. 2010;31:1726–33.
Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 2009;11:R27.
Wu XJ, Li Y, Liu D, Zhao LD, Bai B, Xue MH. MiR-27a as an oncogenic microRNA of hepatitis B virus-related hepatocellular carcinoma. Asian Pac J Cancer Prev. 2013;14:885–9.
Li W, Liu M, Feng Y. Downregulated miR-646 in clear cell renal carcinoma correlated with tumour metastasis by targeting the nine one binding protein (NOB1). Br J Cancer. 2014;111(6):1188–200.
Shen L, Wang P, Yang J, Li X. MicroRNA-217 regulates WASF3 expression and suppresses tumor growth and metastasis in osteosarcoma. PLoS One. 2014;9(10), e109138.
Sun XH, Geng XL, Zhang J. Zhang C.miRNA-646 suppresses osteosarcoma cell metastasis by downregulating fibroblast growth factor 2 (FGF2). Tumour Biol. 2015;36(3):2127–34.
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We thank Dr. Heydari, Dr. Mousavi and Dr. Alizadeh for their technical assistance in this article.
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This article has been retracted at the request of the Editor-in-Chief, the International Society of Oncology and BioMarkers (ISOBM) and the Publisher per the Committee on Publication Ethics guidelines. The article shows evidence of irregularities in authorship during the submission process, there is strong reason to believe that the peer review process was compromised and there are similarities with the following articles which were all submitted within a close timeframe:
Masoomeh Dadpay, Mojtaba Zarea, Rahman Ghaffarzadegan Rabati, Bijan Rezakhaniha, Babak Barari, Vahid Behnod, Katayoun Ziari, Upregulation of miR-21 and downregulation of miR-494 may serve as emerging molecular biomarkers for prediagnostic samples of subjects who developed nasopharyngeal carcinoma associates with lymph node metastasis and poor prognosis. Tumor Biol. First Online: 21 August 2015 DOI: 10.1007/s13277-015-3905-1
Date received: 27 June 2015
Seyyed Hasan Karbasy, Afshin Taheriazam, Alireza Mirghasemi, Farnoush Sedaghati, Mohammadreza Shakeri, Emad Yahaghi, Reza Bahador, Upregulation of miR-300 and downregulation of miR-125b act as potential predictor biomarkers in progression, metastasis, and poor prognosis of osteosarcoma. Tumor Biol. First Online: 02 September 2015 DOI: 10.1007/s13277-015-4000-3
Date received: 24 July 2015
The retracted article was received: 5 July 2015.
As such the validity of the content of this article cannot be verified.
An erratum to this article is available at http://dx.doi.org/10.1007/s13277-016-5478-z.
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Azam, A.T., Bahador, R., Hesarikia, H. et al. RETRACTED ARTICLE: Downregulation of microRNA-217 and microRNA-646 acts as potential predictor biomarkers in progression, metastasis, and unfavorable prognosis of human osteosarcoma. Tumor Biol. 37, 5769–5773 (2016). https://doi.org/10.1007/s13277-015-3821-4
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DOI: https://doi.org/10.1007/s13277-015-3821-4