A novel long non-coding RNA-ARA: Adriamycin Resistance Associated

被引：103

作者：

Jiang, Min ^{[1
,3
]}

Huang, Ou ^{[1
]}

Xie, Zuoquan ^{[2
]}

Wu, Shuchao ^{[2
]}

Zhang, Xi ^{[1
]}

Shen, Aijun ^{[2
]}

Liu, Hongchun ^{[2
]}

Chen, Xiaosong ^{[1
]}

Wu, Jiayi ^{[1
]}

Lou, Ying ^{[1
]}

Mao, Yan ^{[1
]}

Sun, Kan ^{[4
]}

Hu, Shudong ^{[5
]}

Geng, Meiyu ^{[2
]}

Shen, Kunwei ^{[1
]}

机构：

[1] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Comprehens Breast Hlth Ctr, Shanghai 200025, Peoples R China

[2] Chinese Acad Sci, Shanghai Inst Mat Med, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China

[3] Soochow Univ, Affiliated Hosp 1, Dept Breast Surg, Suzhou 215006, Peoples R China

[4] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Endocrinol & Metab, Shanghai 200025, Peoples R China

[5] Shanghai Jiao Tong Univ, Ruijin Hosp, Sch Med, Dept Radiol, Shanghai 200025, Peoples R China

来源：

BIOCHEMICAL PHARMACOLOGY | 2014年 / 87卷 / 02期

关键词：

Adriamycin Resistance; Long non-coding RNA; ARA: Adriamycin resistance associated; Breast cancer; Liver cancer; HUMAN CANCER-CELLS; MULTIDRUG-RESISTANCE; DRUG-RESISTANCE; EXPRESSION; APOPTOSIS; DOXORUBICIN; EVOLUTION; CARCINOMA; CYCLE;

D O I：

10.1016/j.bcp.2013.10.020

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Long non-coding RNAs (IncRNAs) 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 IncRNA-UCA1 induced drug resistance in adriamycin chemotherapy. However, the contributions of IncRNAs to adriamycin resistance in cancers remain largely unknown. To address this issue, we performed a genome-wide IncRNA microarray analysis in adriamycin resistant MCF-7/ADR and parental MCF-7 cells, and revealed differential expression of IncRNAs in distinct category and chromosome distribution patterns. A specific differentially expressed IncRNA (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 IncRNA 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 IncRNA level. (C) 2013 Elsevier Inc. All rights reserved.

引用

页码：254 / 283

页数：30

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