A long non-coding RNA contributes to doxorubicin resistance of osteosarcoma
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Long non-coding RNAs (lncRNAs) are emerging in molecular biology as crucial regulators of cancer. Although the aberrant expression of lncRNAs has been observed in osteosarcoma (OS), the molecular mechanisms underlying lncRNAs in doxorubicin resistance of OS still unknown. In the current study, we investigated a novel lncRNA, termed ODRUL (osteosarcoma doxorubicin-resistance related up-regulated lncRNA), and evaluated its role in the occurrence of doxorubicin resistance in OS. LncRNA microarray revealed that lncRNA ODRUL was the most up-regulated expressed in the doxorubicin-resistant OS cell line. Quantitative real-time PCR (qRT-PCR) confirmed that lncRNA ODRUL was higher in different doxorubicin-resistant OS cell lines and lower in different doxorubicin-sensitive OS cell lines. Moreover, we showed that lncRNA ODRUL was increased in specimens of OS patients with a poor chemoresponse and lung metastasis. We further demonstrated that lncRNA ODRUL inhibition could inhibit OS cell proliferation, migration, and partly reversed doxorubicin resistance in vitro. In addition, we found that the expression of classical drug resistance-related ATP-binding cassette, subfamily B, member 1 (ABCB1) gene was decreased after the lncRNA ODRUL knockdown. Thus, we concluded that lncRNA ODRUL may act as a pro-doxorubicin-resistant molecule through inducing the expression of the classical multidrug resistance-related ABCB1 gene in osteosarcoma cells .These findings may provide a novel target for reversing doxorubicin resistance in OS.
KeywordsLncRNA ODRUL Osteosarcoma Doxorubicin resistance
Long non-coding RNA
Osteosarcoma doxorubicin resistance-related up-regulated lncRNA
This project was supported by a Grant from the National Natural Science Foundation of China (NSFC No. 81572630), Shanghai Pujiang Program of Shanghai Science and Technology Commission (NO.13PJD023) and Shanghai Jiaotong University Medical-Engineering Cross Research Fund (NO.YG2012MS49).
- 12.Milhem MM, Knutson T, Yang S, Zhu D, Wang X, Leslie KK and Meng X. Correlation of MTDH/AEG-1 and HOTAIR expression with metastasis and response to treatment in sarcoma patients. J Cancer Sci Ther. 2011;S5Google Scholar
- 22.Okada T, Tanaka K, Nakatani F, Sakimura R, Matsunobu T, Li X, et al. Involvement of P-glycoprotein and MRP1 in resistance to cyclic tetrapeptide subfamily of histone deacetylase inhibitors in the drug-resistant osteosarcoma and Ewing’s sarcoma cells. Int J Cancer. 2006;118:90–7.CrossRefPubMedGoogle Scholar
- 25.Stewart TA, Azimi I, Thompson EW, Roberts-Thomson SJ, Monteith GR. A role for calcium in the regulation of ATP-binding cassette, sub-family C, member 3 (ABCC3) gene expression in a model of epidermal growth factor-mediated breast cancer epithelial-mesenchymal transition. Biochem Biophys Res Commun. 2015;458:509–14.CrossRefPubMedGoogle Scholar