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. 2020 Jan 15:12:303-311.
doi: 10.2147/CMAR.S232994. eCollection 2020.

Siva 1 Inhibits Cervical Cancer Progression and Its Clinical Prognosis Significance

Ting Liu  1 , Yifei Ma  2 , Zhiling Wang  1 , Wenjing Zhang  1 , Xingsheng Yang  1
Affiliations

Siva 1 Inhibits Cervical Cancer Progression and Its Clinical Prognosis Significance

Ting Liu et al. Cancer Manag Res. .

Abstract

Background: Cervical cancer is the second most common female malignancies. But the exact etiology of cervical cancer is still under investigation. Recent observations revealed that the loss expression of Siva 1 was related to several different types of tumors. It could play an indispensable role in both exogenous and endogenous apoptotic signaling pathways. Nevertheless, the relationship between Siva 1 expression and cervical cancer progression has not yet been fully clarified. This study aimed to explore the functional role of Siva1 in cervical cancer.

Materials and methods: In this present experiment, expression of Siva 1 was detected in 87 cervical cancer, 34 CIN and 20 normal samples by immunohistochemistry. The correlation of Siva 1 expression and overall survival times (OS) was analyzed by Kaplan-Meier analysis. We up-regulated the expression of Siva 1 by plasmid pCMV3-Siva 1 in C33A cells. CCK8, flow cytometry, wound-healing, and transwell assays were performed to examine the influences of Siva 1 expression on cell proliferation, apoptosis, migration and invasion.

Results: The expression of Siva 1 was decreased in cervical cancer tissues compared with CIN and normal tissues. In addition, the Siva 1 immunoreactivity was significantly associated with tumor differentiation. Patients with Siva 1 negative staining exhibited a significantly decreased overall survival. Then, we established stable Siva 1 ectopic expression cells, and we found that elevated expression of Siva 1 promoted apoptosis, inhibited proliferation, and suppressed migration and invasion of cervical cancer cells.

Conclusion: The present study revealed a crucial role of Siva 1 in tumor progression and it may be a valuable prognostic indicator of cervical cancer.

Keywords: Siva 1; apoptosis; cervical cancer; prognosis; proliferation.

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Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Immunohistochemical staining of Siva 1 in normal cervical tissues, CIN tissues and cervical cancer tissues. The expression of Siva 1 in was downregulated in cervical cancer tissues compared with normal tissues and CIN.
Figure 2
Figure 2
Kaplan–Meier curves based on Siva 1 expression.
Figure 3
Figure 3
Siva 1 expression in three cervical cancer cell lines and its effects on cell proliferation.(A) The protein levels of Siva 1 were detected by Western blot in C33A, CaSki and SiHa cells. (B) Establishment of stable transfected cells of ectopic expression of Siva 1. C33A cells were transfected with plasmid pCMV3-Siva 1 and underwent G418 selection. Transfection efficiency was determined by Western blot and qRT-PCR. (C) CCK-8 assay result showed that up-regulation of Siva 1 inhibited cell proliferation of cervical cancer. **P<0.01 compared with the control groups.
Figure 4
Figure 4
Overexpression of Siva 1 promotes cell apoptosis. (A, B) Overexpression of Siva 1 by pCMV3-Siva 1 induced both early and late apoptosis in C33A cells by flow cytometry. (C) Western blot analysis showed that enforced expression of Siva 1 increased the expression of cleaved caspase3 and Bax and reduced the expression of Bcl-2 in cervical cancer cells. *P<0.05, **P<0.01.
Figure 5
Figure 5
Overexpression of Siva 1 suppresses cervical cancer cell migration and invasion. (A) Up-regulation of Siva 1 inhibited the cell migration of C33A cells by wound-healing assay. (B) Transwell assay results showed that overexpression of Siva 1 suppressed the invasion ability of C33A cells. *P<0.05, **P<0.01.
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