LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1
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Zhu Kun-Peng1,2,*, Ma Xiao-Long1,2,* and Zhang Chun-Lin1,2,*
1Department of Orthopaedic Surgery, Shanghai Tenth People’s Hospital Affiliated to Tongji University, Shanghai 200072, PR China
2Institute of Bone Tumor Affiliated to Tongji University School of Medicine, Shanghai 200072, PR China
*These authors contributed equally to this work and co-first authors
Zhang Chun-Lin, email: [email protected]
Keywords: LncRNA, FENDRR, osteosarcoma, chemoresistance, doxorubicin
Received: April 03, 2017 Accepted: May 07, 2017 Published: May 18, 2017
Long noncoding RNAs (LncRNAs) act as crucial regulators in various cancers including osteosarcoma (OS), yet their potential roles and molecular mechanisms in OS chemoresistance remain unclear. In the present study, we investigated the role and potential regulatory mechanism of the most down-regulated expressed lncRNA, FENDRR screened by our previous lncRNA microarray analysis between the paired doxorubicin-resistant and sensitive human osteosarcoma cell lines (MG63/DXR vs MG63). FENDRR expression was down-regulated in the doxorubicin-resistant OS cell lines and tissues and negatively correlated to the poor prognosis of OS patients. Overexpression of FENDRR suppressed doxorubicin-resistance, G2/M phase of cell cycle, and promoted cell apoptosis of osteosarcoma cells in vitro and tumor growth in vivo whereas FENDRR knockdown had the opposite effects. In addition, we found that FENDRR was mainly located in the cytoplasm and could regulate the drug resistance of osteosarcoma cells by negatively affecting posttranscriptional expression of ABCB1 and ABCC1. Together, our study demonstrated that lncRNA FENDRR may act as an inhibitory molecule of doxorubicin-resistance through down-regulating the expression of ABCB1 and ABCC1 genes in osteosarcoma cells. These findings may extend the function of FENDRR in tumor progression and provide a novel target for reversing OS chemoresistance.
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