title: Long noncoding RNA expression profiles of the doxorubicin-resistant human osteosarcoma cell line MG63/DXR and its parental cell line MG63 as ascertained by microarray analysis.
abstract: Long non-coding RNAs (lncRNAs) are emerging in molecular biology as crucial regulators of cancer. The efficacy of doxorubicin--based chemotherapy in osteosarcoma (OS) is usually limited by acquired drug resistance. To explore the mechanism of chemoresistance of OS in terms of lncRNA, using a human lncRNA-mRNA combined microarray, we identified 3,465 lncRNAs (1,761 up and 1,704 down) and 3,278 mRNAs (1,607 up and 1,671 down) aberrantly expressed in all three sets of doxorubicin-resistant MG63/DXR and their paired parental MG63 cells (fold-change >2.0, P<0.05 and FDR <0.05). Fifteen randomly selected lncRNAs were dysregulated in MG63/DXR cells relative to MG63 cells by qRT-PCR detection, which were consistent with our microarray data. Bioinformatics analysis identified that classical genes and pathways involved in cell proliferation, apoptosis, and drug metabolism were differently expressed in these cell lines. A lncRNA-mRNA co-expression network identified lncRNAs, including ENST00000563280 and NR-036444, may play a critical role in doxorubicin-resistance of OS by interacting with important genes such as ABCB1, HIF1A and FOXC2. Besides, we found that lncRNA ENST00000563280 was distinctly increased in specimens of OS patients with a poor chemoresponse compared to those with a good chemoresponse and the patients of lower expression of it may survive longer than those of higher expression, which suggest that it may serve as a biomarker to predict the chemoresponse and prognosis of osteosarcoma patients. These results provide important insights about the lncRNAs involved in osteosarcoma chemoresistance and lay a solid foundation for uncovering the mechanism ultimately.
authors.affiliation: Department of Orthopaedic Surgery, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University Shanghai 200233, PR China.
authors.forename: Kun-Peng
authors.initials: KP
authors.lastname: Zhu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Tenth People's Hospital Affiliated to Tongji University Shanghai 200072, PR China.
authors.forename: Chun-Lin
authors.initials: CL
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital, Soochow University Shanghai 200233, PR 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 Shanghai 200072, PR China.
authors.forename: Zhong-Sheng
authors.initials: ZS
authors.lastname: Zhu
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D045744:Cell Line, Tumor; D002648:Child; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D062085:RNA, Long Noncoding / Q000235:genetics*; D059467:Transcriptome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D062085:RNA, Long Noncoding; D004317:Doxorubicin
keywords: Osteosarcoma; chemoresistance; drug-resistant; long-noncoding RNA