title: Differential microRNA expression signatures and cell type-specific association with Taxol resistance in ovarian cancer cells.
abstract: Paclitaxel (Taxol) resistance remains a major obstacle for the successful treatment of ovarian cancer. MicroRNAs (miRNAs) have oncogenic and tumor suppressor activity and are associated with poor prognosis phenotypes. miRNA screenings for this drug resistance are needed to estimate the prognosis of the disease and find better drug targets. miRNAs that were differentially expressed in Taxol-resistant ovarian cancer cells, compared with Taxol-sensitive cells, were screened by Illumina Human MicroRNA Expression BeadChips. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to identify target genes of selected miRNAs. Kaplan-Meier survival analysis was applied to identify dysregulated miRNAs in ovarian cancer patients using data from The Cancer Genome Atlas. A total of 82 miRNAs were identified in ovarian carcinoma cells compared to normal ovarian cells. miR-141, miR-106a, miR-200c, miR-96, and miR-378 were overexpressed, and miR-411, miR-432, miR-494, miR-409-3p, and miR-655 were underexpressed in ovarian cancer cells. Seventeen miRNAs were overexpressed in Taxol-resistant cells, including miR-663, miR-622, and HS_188. Underexpressed miRNAs in Taxol-sensitive cells included miR-497, miR-187, miR-195, and miR-107. We further showed miR-663 and miR-622 as significant prognosis markers of the chemo-resistant patient group. In particular, the downregulation of the two miRNAs was associated with better survival, perhaps increasing the sensitivity of cancer cells to Taxol. In the chemo-sensitive patient group, only miR-647 could be a prognosis marker. These miRNAs inhibit several interacting genes of p53 networks, especially in TUOS-3 and TUOS-4, and showed cell line-specific inhibition effects. Taken together, the data indicate that the three miRNAs are closely associated with Taxol resistance and potentially better prognosis factors. Our results suggest that these miRNAs were successfully and reliably identified and would be used in the development of miRNA therapies in treating ovarian cancer.
authors.affiliation: Cancer Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Yong-Wan
authors.initials: YW
authors.lastname: Kim
authors.affiliation: Cancer Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Kim
authors.affiliation: Cancer Research Institute of Medical Science, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Doin
authors.initials: D
authors.lastname: Jeon
authors.affiliation: Brain Tumor Center, Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, TX, USA.
authors.forename: Juinn-Lin
authors.initials: JL
authors.lastname: Liu
authors.affiliation: Cancer Rehab Laboratory, RH Healthcare Systems Inc, TX, USA.
authors.forename: Helena Suhyun
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Harvard Medical School and Wellman Center for Photomedicine, Cambridge, MA, USA.
authors.forename: Jin Woo
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Department of Obstetrics and Gynecology, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Woong Shick
authors.initials: WS
authors.lastname: Ahn
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D035683:MicroRNAs / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000401:mortality; D017239:Paclitaxel / Q000494:pharmacology*; D059467:Transcriptome
chemical_list: D035683:MicroRNAs; D017239:Paclitaxel
keywords: Kaplan–Meier survival analysis; Taxol resistance; microRNA; ovarian cancer