Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells

Pei Ning Yu, Ming D. Yan, Hung-Cheng Lai, Rui Lan Huang, Yu Ching Chou, Wen Chi Lin, Li Tzu Yeh, Ya W. Lin

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

Drug resistance is an obstacle to the treatment of ovarian cancer. Using a unique cell model, we have proven previously that a subpopulation of ovarian cancer cells is more resistant to cisplatin than are the original cells. MicroRNAs (miRNAs), small noncoding RNAs, are involved in many biological events in cancer cells. In our study, we explored whether miRNAs are involved in cisplatin resistance of ovarian cancer cells. Cisplatin-resistant cells expressed a lower level of miR-29a/b/c. Manipulation of microRNA-29 (miR-29) expression modulated cisplatin sensitivity of CP70, HeyC2, SKOV3 and A2780 ovarian cancer cells. Knockdown of miR-29a/b/c increased the ability of cells to escape cisplatin-induced cell death partly through upregulation of collagen type I alpha 1 (COL1A1) and increased the activation of extracellular signal-regulated kinase 1/2 and inactivation of glycogen synthase kinase 3 beta. When combined with cisplatin treatment, knockdown of miR-29 decreased the amount of the active form of caspase-9 and caspase-3. Ectopic expression of miR-29 alone or in combination with cisplatin treatment efficaciously reduced the tumorigenicity of CP70 cells in vivo. Our data show that downregulation of miR-29 increases cisplatin resistance in ovarian cancer cells. Taken together, these data suggest that overexpression of miR-29 is a potential sensitizer to cisplatin treatment that may have therapeutic implications.

Original languageEnglish
Pages (from-to)542-551
Number of pages10
JournalInternational Journal of Cancer
Volume134
Issue number3
DOIs
Publication statusPublished - 2013
Externally publishedYes

Fingerprint

MicroRNAs
Ovarian Neoplasms
Cisplatin
Down-Regulation
Small Untranslated RNA
Mitogen-Activated Protein Kinase 3
Caspase 9
Mitogen-Activated Protein Kinase 1
Drug Resistance
Caspase 3
Cell Death
Up-Regulation

Keywords

  • cisplatin resistance
  • COL1A1
  • miR-29
  • ovarian cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells. / Yu, Pei Ning; Yan, Ming D.; Lai, Hung-Cheng; Huang, Rui Lan; Chou, Yu Ching; Lin, Wen Chi; Yeh, Li Tzu; Lin, Ya W.

In: International Journal of Cancer, Vol. 134, No. 3, 2013, p. 542-551.

Research output: Contribution to journalArticle

Yu, Pei Ning ; Yan, Ming D. ; Lai, Hung-Cheng ; Huang, Rui Lan ; Chou, Yu Ching ; Lin, Wen Chi ; Yeh, Li Tzu ; Lin, Ya W. / Downregulation of miR-29 contributes to cisplatin resistance of ovarian cancer cells. In: International Journal of Cancer. 2013 ; Vol. 134, No. 3. pp. 542-551.
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