title: A novel long non-coding RNA-ARA: adriamycin resistance-associated.
abstract: Long non-coding RNAs (lncRNAs) are emerging as an integral functional component of human genome and have been investigated as critical regulators in molecular biology of cancer. A recent study reported that lncRNA-UCA1 induced drug resistance in adriamycin chemotherapy. However, the contributions of lncRNAs to adriamycin resistance in cancers remain largely unknown. To address this issue, we performed a genome-wide lncRNA microarray analysis in adriamycin resistant MCF-7/ADR and parental MCF-7 cells, and revealed differential expression of lncRNAs in distinct category and chromosome distribution patterns. A specific differentially expressed lncRNA (Adriamycin Resistance Associated, termed ARA) was validated in MCF-7/ADR and HepG2/ADR cells. ARA is derived from an intron of PAK3 gene, predicted to contain several stable hairpins in secondary structure and has conservative sequences in primates. ARA expression is significantly associated with adriamycin sensitivity in a panel of breast and liver cancer cell lines and is markedly up-regulated in parental sensitive MCF-7 and HepG2 cell lines after receiving adriamycin treatment. The functions of ARA were assessed by silencing this lncRNA in vitro, and we found that ARA knockdown reduced the proliferation, induced cell death, G2/M arrest and migration defects. Furthermore, microarray transcriptomic analysis was carried out to comprehensively depict the ARA-regulated genes. We showed that ARA can modulate multiple signalling pathways, including MAPK signalling pathway, metabolism pathways, cell cycle and cell adhesion-related biological pathways, and regulate cellular processes, including transcriptional processes and protein binding function. Overall, our results indicate novel insights of adriamycin resistance in lncRNA level.
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China; Department of Breast Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, China.
authors.forename: Min
authors.initials: M
authors.lastname: Jiang
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ou
authors.initials: O
authors.lastname: Huang
authors.affiliation: Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Zuoquan
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Shuchao
authors.initials: S
authors.lastname: Wu
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Shen
authors.affiliation: Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors.forename: Hongchun
authors.initials: H
authors.lastname: Liu
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Chen
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wu
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Lou
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Kan
authors.initials: K
authors.lastname: Sun
authors.affiliation: Department of Radiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Shudong
authors.initials: S
authors.lastname: Hu
authors.affiliation: Division of Antitumor Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. Electronic address: meiyu_geng@yeah.net.
authors.forename: Meiyu
authors.initials: M
authors.lastname: Geng
authors.affiliation: Comprehensive Breast Health Centre, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China. Electronic address: kunwei_shen@yeah.net.
authors.forename: Kunwei
authors.initials: K
authors.lastname: Shen
mesh_terms: D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000502:physiology*; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D061986:MCF-7 Cells; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000187:drug effects*; D015203:Reproducibility of Results; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D062085:RNA, Long Noncoding; D004317:Doxorubicin
keywords: ARA: Adriamycin resistance associated; Adriamycin Resistance; Breast cancer; Liver cancer; Long non-coding RNA