Cancer Res Treat.  2019 Oct;51(4):1653-1665. 10.4143/crt.2018.544.

Paip1 Indicated Poor Prognosis in Cervical Cancer and Promoted Cervical Carcinogenesis

• Li N
• Piao J
• Wang X
• Kim KY
• Bae JY
• Ren X
• Lin Z

• KMID: 2460613
• DOI: http://doi.org/10.4143/crt.2018.544

Abstract

PURPOSE
This study was aimed to investigate the role of poly(A)-binding protein-interacting protein 1 (Paip1) in cervical carcinogenesis.
MATERIALS AND METHODS
The expression of Paip1 in normal cervical epithelial tissues and cervical cancer (CC) tissues were detected by immunohistochemistry. In vivo and in vitro assays were performed to validate effect of Paip1 on CC progression.
RESULTS
Paip1 was found to be up-regulated in CC, which was linked with shorter survival. Knockdown of Paip1 inhibited cell growth, induced apoptosis and cell cycle arrest in CC cells, whereas its overexpression reversed these effects. The in vivo tumor model confirmed the pro-tumor role of Paip1 in CC growth.
CONCLUSION
Altogether, the investigation demonstrated the clinical significance of Paip1 expression, which prompted that the up-regulated of Paip1 can presumably be a potential prognostic and progression marker for CC.

Keyword

Paip1; Uterine cervical neoplasms; Proliferation; Cell cycle; Apoptosis

MeSH Terms

Apoptosis
Carcinogenesis*
Cell Cycle
Cell Cycle Checkpoints
Immunohistochemistry
In Vitro Techniques
Prognosis*
Uterine Cervical Neoplasms*

Figure

• 

  Fig. 1. Poly(A)-binding protein-interacting protein 1 (Paip1) expression was significantly up-regulated in cervical cancer (CC). (A, B) Analysis of Paip1 expression in Oncomine data set. (C) Paip1 protein staining was negative in cervical epithelial tissues. (D, E) Paip1 protein staining was positive in dysplastic cells of cervical intraepithelial neoplasia. (F) Paip1 protein staining was positive in adenocarcinoma. (G, H) Paip1 protein staining was positive in squamous cervical cancers. (I) Relationship between Paip1 expression and clinicopathological significance of CCs. LN, lymph node.

• 

  Fig. 2. Poly(A)-binding protein-interacting protein 1 (Paip1) expression was associated with poor outcome in cervical cancer (CC). (A) The implication of Paip1 in the survival of patients with CC was determined in the Human Protein Atlas’s cohort. (B, C) Kaplan-Meier survival analyses were conducted to evaluate the influence of Paip1 on patient disease-free survival (DFS) (B) and overall survival (OS) (C). (D-G) Kaplan-Meier survival curves of CC patients in early and late stage.

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  Fig. 3. Poly(A)-binding protein-interacting protein 1 (Paip1) attenuated the ability of proliferation of cervical cancer (CC) cells in vitro. (A) The protein expression of Paip1 in CC cells was examined by western blot analysis. Actin was used as a loading control. (B) The protein expression of Paip1 in the constructed CC cells was confirmed by western blot analysis. Actin was used as a loading control. (C, D) Cell proliferation was examined by MTT (C) and colony formation (D) in the constructed cells. Data are represented as mean±standard error of mean of at least three independent experiments, **p < 0.01.

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  Fig. 4. Poly(A)-binding protein-interacting protein 1 (Paip1) regulated cell cycle progression of cervical cancer (CC) cell lines in vitro. (A) Cell cycle distribution was identified by flow cytometry. Data are represented as mean±standard error of mean of at least three independent experiments. **p < 0.01. (B) The protein expression of molecules associated with the cell cycle in the constructed CC cells was confirmed by western blot analysis. Actin was used as a loading control.

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  Fig. 5. Poly(A)-binding protein-interacting protein 1 (Paip1) regulated cell apoptosis of cervical cancer (CC) cell lines in vitro. (A) Cell apoptosis of CC cells was detected by flow cytometry. Data were presented as the mean±standard deviation. **p < 0.01. (B) Western blot analysis of apoptosis-related protein in the constructed CC cells. Actin was used as a loading control. PI, propidium iodide.

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  Fig. 6. Poly(A)-binding protein-interacting protein 1 (Paip1) promoted tumor growth in vivo. (A, B) Indicated cells were injected into the nude mice, and statistical comparison of the differences in tumor weight was shown. (C, D) Expression levels of Ki-67, Bcl-2, and Bax in the xenograft tumors tissues were detected by immunohistochemistry.

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  Fig. 7. Schematic diagram. Poly(A)-binding protein-interacting protein 1 (Paip1) enhanced proliferation and inhibited apoptosis in cervical cancer.

Reference

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