CIAPIN1 nuclear accumulation predicts poor clinical outcome in epithelial ovarian cancer

Abstract

BackgroundEpithelial ovarian cancer (EOC) is an aggressive disease with poor prognosis. The expression of cytokine-induced apoptosis inhibitor 1 (CIAPIN1) correlates with the malignant progression of several cancers. However, the relationship between the subcellular localization of CIAPIN1 and clinical characteristics in EOC remains unclear.MethodsImmunohistochemistry was performed to detect CIAPIN1 expression in 108 EOC tissues. CIAPIN1 expressions in eight fresh EOC tissues were detected by Western blotting. The relationship between CIAPIN1 subcellular expression and patients’ clinicopathological features, including prognosis, was evaluated. Immunohistochemistry and immunofluorescence were employed to assess the CIAPIN1 subcellular localization in the EOC cell lines A2780 and HO8910. In addition, all patients were followed up to assess the prognostic value of CIAPIN1 in patients with EOC.ResultsCIAPIN1 is highly expressed in EOC, but is present at low levels in paired non-cancerous ovarian epithelial tissues. The results of Western blotting were in accordance with the immunohistochemical results. Poor differentiation of the tumors and EOC cell lines correlated with higher levels of CIAPIN1 nuclear expression. CIAPIN1 nuclear expression significantly correlated with the Federation International of Gynecology and Obstetrics (FIGO) stage and histological differentiation (P = 0.034 and P < 0.0001, respectively). Moreover, nuclear localization of CIAPIN1 was selected as an unfavorable prognostic factor by both univariate and multivariate analyses ( P < 0.001). However, no significant correlations were observed between cytoplasmic localization of CIAPIN1 and clinicopathological parameters.ConclusionsCIAPIN1 might play a crucial role in the differentiation of EOC cells. Elevated expression of nuclear CIAPIN1 negatively correlated with the survival of EOC patients, suggesting that nuclear CIAPIN1 might serve as a prognostic biomarker for EOC patients.

Cytokine‐induced apoptosis inhibitor 1 (CIAPIN1) accelerates vascular remodelling via p53 and JAK2‐STAT3 regulation in vascular smooth muscle cells

“…Although CIAPIN1 protein is known to express in both the cytoplasm and nucleus, CIAPIN1 actively translocated into the nucleus by ROS induction (K. A. Park et al, 2011) and strongly accumulated in nucleus as severe proliferative disease progression (Cai et al, 2012) and proliferative cells (Figure 5i,j), implicating its role in gene regulation.…”

“…Recent studies suggest that CIAPIN1 nuclear accumulation negatively correlates with the survival of epithelial ovarian cancer (EOC) patients and plays an important role in cancer progression (Cai et al, 2012). In addition, cytoplasmic CIAPIN1 is actively translocated into the nucleus by reactive oxygen species (ROS)-inducing 6-hydroxydopamine in dopaminergic neuronal cells (MN9D) and rat brain (Park et al, 2011).…”

“…Wang et al, 2019), although the effects on proliferation are somewhat controversial. Moreover, several studies have identified CIAPIN1 as an independent prognostic marker of poor outcomes in patients (Cai et al, 2012;Nymoen et al, 2015).…”

CIAPIN1 and ABCA13 are markers of poor survival in metastatic ovarian serous carcinoma

“…Ciapin1 additionally regulates cell differentiation, organ development and cellular stress response [ 20 ]. Nuclear expression of CIAPIN1 was reported to be associated with poor prognosis in a study of 108 primary OC [ 21 ]. In our series, this protein was predominantly localized to the cytoplasm, nuclear expression being too infrequent to be considered of clinical relevance.…”

CIAPIN1 targets Na+/H+ exchanger 1 to mediate K562 chronic myeloid leukemia cells’ differentiation via ERK1/2 signaling pathway

“…Intensive studies have been conducted to identify its function and molecular mechanism. For example, people have reported the expression of CIAPIN1 was associated with the differentiation of human colorectal cancer cells and epithelial ovarian cancer cells [22,23]. However, the potential effect of CIAPIN1 on regulating the differentiation of leukemia cells has not been reported.…”