title: A long non-coding RNA contributes to doxorubicin resistance of osteosarcoma.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, 301, Yan-chang Middle Road, Shanghai, 200072, People's Republic of China. shzhangchunlin123@163.com.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai, 200233, People's Republic of China.
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Soochow University, Shanghai, 200233, People's Republic of China.
authors.forename: Guo-Qi
authors.initials: GQ
authors.lastname: Shen
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University, 301, Yan-chang Middle Road, Shanghai, 200072, People's Republic of China.
authors.forename: Zhong-Sheng
authors.initials: ZS
authors.lastname: Zhu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000293:Adolescent; D000328:Adult; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D002648:Child; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D062085:RNA, Long Noncoding; D004317:Doxorubicin
keywords: Doxorubicin resistance; LncRNA; ODRUL; Osteosarcoma