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. 2019 Jan;17(1):564-570.
doi: 10.3892/ol.2018.9524. Epub 2018 Sep 28.

Capn4 regulates migration and invasion of ovarian carcinoma cells via targeting osteopontin-mediated PI3K/AKT signaling pathway

Yuanyuan Chen  1 , Gang Wang  1 , Yingmei Wang  1 , Xiaoli Gao  1 , Kan Wang  1 , Jie Li  1 , Fengxia Xue  1
Affiliations

Capn4 regulates migration and invasion of ovarian carcinoma cells via targeting osteopontin-mediated PI3K/AKT signaling pathway

Yuanyuan Chen et al. Oncol Lett. 2019 Jan.

Abstract

Previous studies have demonstrated that calpain small subunit 4 (Capn4) is able to regulate the viability and metastasis of cancer cells. However, the regulatory effects and underlying molecular mechanism of Capn4 in ovarian carcinoma cells are not well understood. The purpose of the present study was to investigate the role of Capn4 in ovarian carcinoma cells and analyze the possible mechanism mediated by Capn4. The expression levels of Capn4 and osteopontin (OPN) were determined and the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway was analyzed in ovarian carcinoma cells. The results of the present study revealed that Capn4 and OPN were overexpressed in clinical ovarian carcinoma tissues and ovarian carcinoma cells. Capn4 silencing downregulated OPN expression, and suppressed ovarian carcinoma cell viability and migration. Capn4 silencing enhanced apoptosis of ovarian carcinoma cells by increasing activity of the capase-3 apoptosis signaling pathway. Capn4 promoted the metastasis of ovarian carcinoma cells by interacting with the PI3K/AKT signaling pathway via upregulation of OPN expression. In conclusion, the results of the present study indicate that Capn4 may be a potential therapeutic target for the treatment of ovarian carcinoma.

Keywords: calpain small subunit 4; invasion; migration; osteopontin; ovarian carcinoma; phosphoinositide 3-kinase/protein kinase B.

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Figures

Figure 1.
Figure 1.
Expression levels and clinical significance of Capn4 in ovarian carcinoma. (A) Capn4 presents increased expression in ovarian carcinoma tissues compared with normal ovarian epithelial tissues. (B) Gene and (C) protein expression levels of Capn4 in ovarian carcinoma tissues and normal ovarian epithelial tissues. (D) Analysis of the association between Capn4 expression and survival of ovarian carcinoma patients. Capn4, calpain small subunit 4. **P<0.01 vs. Normal.
Figure 2.
Figure 2.
Knockdown of Capn4 inhibits the viability and aggressiveness of ovarian carcinoma cells. (A) Expression levels of Capn4 in ovarian carcinoma cells (SKOV3) and normal ovarian epithelial cells (IOSE80). (B) Capn4 silencing inhibited ovarian cancer cells SKOV3 viability in vitro. Capn4 silencing inhibited (C) migration and (D) invasion of SKOV3 cells. Capn4, calpain small subunit 4; siR, siRNA. **P<0.01 vs. siR-Vector.
Figure 3.
Figure 3.
Knockdown of Capn4 promotes apoptosis of ovarian carcinoma cells via the capase-3 apoptosis signaling pathway. (A) Capn4 silencing promoted the apoptosis of SKOV3 cells induced by cisplatin. (B) Capn4 silencing increased the expression levels of the pro-apoptotic caspase-3 and caspase-9 in SKOV3 cells. (C) Capn4 silencing decreased the expression levels of the anti-apoptotic Bcl-2 and Bcl-w in SKOV3 cells. Capn4, calpain small subunit 4; siR, siRNA; Bcl, B-cell lymphoma; Q, quadrant. **P<0.01 vs. siR-Vector.
Figure 4.
Figure 4.
Knockdown of Capn4 inhibits ovarian carcinoma cells metastasis via the OPN-mediated PI3K/AKT signaling pathway. (A) Capn4 silencing increased OPN, PI3K and AKT expression in SKOV3 cells. (B) Capn4 silencing increased the levels of p-PI3K and p-AKT in SKOV3 cells. (C) OPN silencing downregulated the expression and levels of p-PI3K and p-AKT in SKOV3 cells. PI3K inhibitor inhibited (D) migration and (E) invasion of SKOV3 cells in Capn4-silenced SKOV3 cells. Capn4, calpain small subunit 4; siR, siRNA; OPN, osteopontin; PI3K, phosphoinositide 3-kinase; AKT, protein kinase B; p-, phospho-; NS, not significant; PI3KIR, PI3K inhibitor. **P<0.01 vs. control or siR-Capn4+PI3KIR.
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