Open Access

RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells

  • Authors:
    • Dongwei Mao
    • Jianhua Che
    • Shiyu Han
    • Honghui Zhao
    • Yumei Zhu
    • Hong Zhu
  • View Affiliations

  • Published online on: August 21, 2015     https://doi.org/10.3892/mmr.2015.4238
  • Pages: 6635-6641
  • Copyright: © Mao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

CLN3 is a recently identified anti-apoptotic gene, which has been demonstrated to be highly expressed in a diverse range of cancer cell lines, including ovarian cancer. In the present study, RNA interference, mediated by a lentivirus expressing CLN3 short hairpin RNA (shRNA) was utilized to knockdown the expression of CLN3 in the A2780 human ovarian cancer cell line, and its cisplatin‑resistant and carboplatin‑resistant sublines, A2780/DDP and A2780/CBP cells. It was revealed that the mRNA and protein expression levels of CLN3 were significantly reduced in the CLN3‑specific shRNA‑transduced cells, compared with the untransduced and control shRNA‑transduced cells. In addition, specific knockdown of CLN3 in these cells inhibited cell proliferation and led to cell cycle arrest at the G0/G1 phase, with eventual apoptosis. CLN3 knockdown caused increases in the levels of Bax, FAX, cleaved‑caspase 3, cleaved‑caspase 8 and cleaved‑RARP, but decreased the level of Bcl‑2. Finally, it was observed that CLN3 depletion markedly reduced the half maximum inhibitory concentration in the A2780/DDP and A2780/CBP cells. Taken together, these data suggested that CLN3 is involved in tumorigenesis and drug resistance in ovarian cancer, and may serve as a promising therapeutic target for its treatment.
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November-2015
Volume 12 Issue 5

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Mao D, Che J, Han S, Zhao H, Zhu Y and Zhu H: RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells. Mol Med Rep 12: 6635-6641, 2015.
APA
Mao, D., Che, J., Han, S., Zhao, H., Zhu, Y., & Zhu, H. (2015). RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells. Molecular Medicine Reports, 12, 6635-6641. https://doi.org/10.3892/mmr.2015.4238
MLA
Mao, D., Che, J., Han, S., Zhao, H., Zhu, Y., Zhu, H."RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells". Molecular Medicine Reports 12.5 (2015): 6635-6641.
Chicago
Mao, D., Che, J., Han, S., Zhao, H., Zhu, Y., Zhu, H."RNAi-mediated knockdown of the CLN3 gene inhibits proliferation and promotes apoptosis in drug-resistant ovarian cancer cells". Molecular Medicine Reports 12, no. 5 (2015): 6635-6641. https://doi.org/10.3892/mmr.2015.4238