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Series GSE181632 Query DataSets for GSE181632
Status Public on Aug 08, 2021
Title Mitochondrial BCRP sustains the proliferation and survival of drug-resistant breast-cancer cells by regulating intracellular ROS
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary ATP-binding cassette (ABC) transporter family are major contributors to the drug-resistance establishment of breast cancer cells. Breast cancer resistant protein (BCRP), one of the ABC transporters, has long been recognized as a pump that effluxes the therapeutic drugs against the concentration gradient. However, recent studies suggest that the biological function of BCRP is not limited in its drug-pump activity. Herein, the role of BCRP in the proliferation and survival of drug-resistant breast cancer cells was investigated. We found that BCRP is not the major drug pump to efflux epirubicin in the resistant cells that express multiple ABC transporters. Silencing of BCRP significantly impairs cell proliferation and induces apoptosis of the resistant cells in vitro and in vivo. RNA-sequencing and high-throughput proteomics suggest that BCRP is an inhibitory factor of oxidative phosphorylation (OXPHOS). Further research suggests that BCRP is localized in the mitochondria of the resistant cells. Knockdown of BCRP elevated the intracellular reactive oxygen species (ROS) level and eventually promotes the cell to undergo apoptosis. This study demonstrated that BCRP exerts important onco-promoting functions in the drug-resistant breast cancer cells independent of its well-recognized drug-efflux activity, which shed new light on understanding the complex functional role of ABC transporters in drug-resistant cells.
 
Overall design For transcriptome RNA sequencing (RNA-Seq), SK/EPI, SK-BR-3, SK/EPI-siBCRP and SK/EPI-siNC cells were prepared in triplicates and lysed by Trizol reagent (Invitrogen). Then the cell lysates were processed and sequence by NovoGene (Beijing, China).
 
Contributor(s) Zhang H, Han X, Wang Z, Wang Z, Cui Y, Tian R, Zhu Y, Han B, Liu H, Zuo X, Ren S, Tian J, Niu R, Zhang F
Citation(s) 34650973
Submission date Aug 07, 2021
Last update date Oct 19, 2021
Contact name He Zhang
E-mail(s) zhanghe1992@tmu.edu.cn
Phone +861360204722
Organization name Tianjin Medical University Cancer Institute and Hospital
Department Public Laboratory
Street address Tianjin 300060
City Tianjin
State/province Tianjin
ZIP/Postal code 300060
Country China
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (12)
GSM5508589 SK-BR-3-1
GSM5508590 SK-BR-3-2
GSM5508591 SK-BR-3-3
Relations
BioProject PRJNA752771
SRA SRP331454

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE181632_SK-BR-3_SK-EPI.txt.gz 1002.5 Kb (ftp)(http) TXT
GSE181632_SK-EPI-sINC_SK-EPI-siBCRP.txt.gz 1.1 Mb (ftp)(http) TXT
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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