4.6 Article

WAVE1 gene silencing via RNA interference reduces ovarian cancer cell invasion, migration and proliferation

Journal

GYNECOLOGIC ONCOLOGY
Volume 130, Issue 2, Pages 354-361

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygyno.2013.05.005

Keywords

WAVE1; Ovarian cancer; RNA interference; Proliferation; Invasion

Funding

  1. National Natural Science Foundation of China [30772034/C0805]
  2. Specialized Research Fund for the Doctoral Program of Higher Education of China [200806310001]
  3. Chongqing Medical University
  4. Medical Science Grant of the First Affiliated Hospital of Chongqing Medical University [YXJJ2009-05]

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Objective. Wiskott-Aldrich syndrome protein family verprolin-homologous protein 1 (WAVEI) has been implicated in cancer cell migration and invasion. We have previously shown that the overexpression of WAVEI in epithelial ovarian cancer (EOC) tissues is associated with a poor prognosis. However, the mechanism of WAVE1 regulating the malignant behaviors in EOC remains unclear. Methods. In the present study, we knocked down WAVEI expression in SKOV3 and OVCAR-3 cells through RNA interference to detect the cell biology and molecular biology changes. Moreover, western-blot was used to investigate the underlying mechanism of WAVEI regulating the proliferative and invasive malignant behaviors in ovarian cancer cells. Results. The down-regulation of WAVE1 had a significant effect on cell morphological changes. WAVEI silencing decreased cell migration, cell invasion, cell adhesion, colony formation and cell proliferation in vitro. In addition, we found that down-regulation of WAVE1 inhibited malignant behaviors in vivo. Furthermore, our study also indicated that the PI3K/AKT and p38MAPK signaling pathways might contribute to WAVEI promotion of ovarian cancer cell proliferation, migration, and invasion. Conclusions. WAVEI might promote the proliferative and invasive malignant behaviors through the activation of the PI3K/AKT and p38MAPK signaling pathways in EOC. (C) 2013 Elsevier Inc. All rights reserved.

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