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Pregled bibliografske jedinice broj: 759131

The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells


Brozovic, Anamaria; Duran, George E.; Wang, Yan C.; Francisco, Brian E; Sikic, Branimir I.
The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells // Molecular Oncology, 9 (2015), 8; 1678-1693 (međunarodna recenzija, članak, znanstveni)


Naslov
The miR-200 family differentially regulates sensitivity to paclitaxel and carboplatin in human ovarian carcinoma OVCAR-3 and MES-OV cells

Autori
Brozovic, Anamaria ; Duran, George E. ; Wang, Yan C. ; Francisco, Brian E ; Sikic, Branimir I.

Izvornik
Molecular Oncology (1574-7891) 9 (2015), 8; 1678-1693

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Carboplatin; drug resistance; epithelial mesenchymal transition; miRNA-200; paclitaxel

Sažetak
We studied the role of miRNA-200 family members in cellular sensitivity to paclitaxel and carboplatin, using two ovarian cancer cell lines, OVCAR-3 and MES-OV, and their paclitaxel resistant variants OVCAR-3/TP and MES-OV/TP. Both resistant variants display a strong epithelial-mesenchymal transition (EMT) phenotype, with marked decreases in expression of miR-200c and miR-141 in OVCAR-3/TP, and down-regulation of all five members of the miR-200 family in MES-OV/TP. Lentiviral transfection of inhibitors of miR-200c or miR-141 in parental OVCAR-3 triggered EMT and rendered the cells resistant to paclitaxel and carboplatin. Conversely, the infection of OVCAR-3/TP cells with retroviral particles carrying the miR-200ab429 and 200c141 clusters triggered a partial mesenchymal to epithelial transition (MET). This partial MET was not sufficient to re-sensitize OVCAR-3/TP cells to paclitaxel. However, the miR-200c/miR-141 cluster transfectants became 6-8x resistant to carboplatin, an unexpected result, whereas miR-200a/miR-200b/miR-429 had no effect. Transfecting the OVCAR-3/TP GFP cells with specific miRNA mimics confirmed these data. MiR-200c and miR-141 mimics conferred resistance to carboplatin in MES-OV/TP cells, similar to OVCAR-3/TP, but sensitized MES-OV to paclitaxel. Several genes involved in balancing oxidative stress were altered in OVCAR-3/TP 200c141 cells compared to controls. The miR-200 family plays major, cell-context dependent roles in regulating EMT and sensitivity to carboplatin and paclitaxel in OVCAR-3 and MES-OV cells.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Autor s matičnim brojem:
Anamaria Brozović, (229956)

Časopis indeksira:


  • Web of Science Core Collection (WoSCC)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE