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Series GSE139043 Query DataSets for GSE139043
Status Public on Oct 18, 2019
Title Downregulation of miR-194-5p induces paclitaxel resistance in ovarian cancer cells by altering MDM2 expression.
Organism Homo sapiens
Experiment type Other
Summary Paclitaxel is a first-line drug for treating epithelial ovarian cancer (EOC). However, prognosis for patients with advanced stage cancer remains poor due to primary or acquired drug resistance. Therefore, overcoming chemoresistance is one of the greatest challenges in treating EOC. In this study, we identified microRNAs (miRNA) that regulate paclitaxel resistance and tested their potential utility as therapeutic targets. Paclitaxel-resistant cell lines were established using two EOC cell lines: SKVO3ip1 and HeyA8. miRNA PCR arrays showed that miR-194-5p was downregulated in paclitaxel-resistant cells. Forced expression of miR-194-5p resensitized resistant cells to paclitaxel. Conversely, miR-194-5p inhibition induced paclitaxel resistance in parental cells. In silico analysis and luciferase reporter assay revealed that MDM2 is a direct target of miR-194-5p. MDM2 was upregulated in paclitaxel resistant cells compared with parental cells. MDM2 inhibition also resensitized resistant cells to paclitaxel and forced MDM2 induced paclitaxel resistance in parental cells. miR-194-5p induced p21 upregulation and G1 phase arrest in resistant cells by downregulating MDM2. Furthermore, a public database showed that high MDM2 expression was associated with a shorter progression-free survival in EOC patients treated with paclitaxel. Collectively, our results show that restoring miR-194-5p expression resensitizes EOCs to paclitaxel, and this may be exploited as a therapeutic option.
 
Overall design We established paclitaxel resistant high grade serous ovarian cancer cell lines (SKOV3ip1-TR and HeyA8-TR) from 2 parental cell lines (SKOV3ip1 and HeyA8),. Then miRNA expression profiles were assessed in these 4 ovarian cancer cell lines by TaqMan miRNA arrays. Relative expression of miRNAs in paclitaxel resistant sublines were calculated when compared with parental cell lines.
 
Contributor(s) Nakamura K, Sawada K
Citation(s) 30774764
Submission date Oct 17, 2019
Last update date Oct 18, 2019
Contact name Kenjiro Sawada
E-mail(s) daasawada@gyne.med.osaka-u.ac.jp
Phone 81-6-6879-5111
Organization name Osaka University Faculty of Medicine
Department Obstetrics and Gynecology
Lab Endocrinology
Street address Yamadaoka 2-15
City Suita
State/province Osaka
ZIP/Postal code 5650871
Country Japan
 
Platforms (1)
GPL27631 TaqMan Array Human MicroRNA A Cards v2.0
Samples (4)
GSM4127998 SKOV3ip1
GSM4127999 SKOV3ip1-TR
GSM4128000 HeyA8
Relations
BioProject PRJNA578133

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
GSE139043_fold-change.txt.gz 3.6 Kb (ftp)(http) TXT
GSE139043_non-normalized.txt.gz 3.2 Kb (ftp)(http) TXT
GSE139043_normalized.txt.gz 5.6 Kb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table
Processed data are available on Series record

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