Functional implications of PABPC1 in the development of ovarian cancer.

Cong Feng,Yu Liu,Li-Li Yang,Yan-Hua Han,Qing-Hua Sheng,Jia Li,Na Qi

doi:10.1515/med-2021-0278

Abstract

This research aimed to probe the expression characteristics of poly(A)-binding protein cytoplasmic 1 (PABPC1) and its role on the phenotype of ovarian cancer (OC) cells and to further investigate the possible underlying mechanism. The expression of PABPC1 was analyzed according to the data from gene expression omnibus, The Cancer Genome Atlas (TCGA) and Oncomine databases and the RNA sequencing data set from TCGA were downloaded for evaluating the prognostic values. We revealed that compared with the healthy samples, PABPC1 was upregulated in OC samples. High expression of PABPC1 had a connection with a shorter survival for patients with OC. Loss and gain of function assays revealed that silencing PABPC1 significantly suppressed the viability, invasion and migration of SK-OV-3 cells, while PABPC1 overexpression in A2780 cells showed the reverse outcomes. Moreover, Western blot demonstrated that silencing PABPC1 notably inactivated the epithelial–mesenchymal transition (EMT) process, while upregulation of PABPC1 promoted the mitigation of epithelial phenotype and the acquisition of mesenchymal phenotype. Taken together, PABPC1 was upregulated in OC cells and served as a carcinogene to promote the OC cell growth and invasion partly by modulating the EMT process, which implied that PABPC1 might be considered as a useful biomarker for OC therapeutics.

Highlights

Ovarian cancer (OC), known as a common malignancy in gynecology, has the highest mortality among the malignant tumors in female reproductive system and seriously threatens women’s life and health [1,2]
We found that poly(A)-binding protein cytoplasmic 1 (PABPC1) displayed a higher expression in OC tissues based on the Bonome Ovarian data set and Yoshihara Ovarian data set from Oncomine database when compared with nontumor tissues (P < 0.01; Figure 1c and d)
A significant upregulation of PABPC1 was shown in all OC cell lines compared to the normal cell line IOSE80 (P < 0.01; Figure 1e), which was in agreement with the outcomes by bioinformatic analysis

Summary

Introduction

Ovarian cancer (OC), known as a common malignancy in gynecology, has the highest mortality among the malignant tumors in female reproductive system and seriously threatens women’s life and health [1,2]. The American Cancer Society estimated approximately 22,530 new cases of OC and 13,980 OC-related deaths in the United States in 2019 [3]. This carcinoma is frequently diagnosed at an advanced stage due to its asymptomatic development and the lack of effective diagnostic approach at an early stage [4,5]. Platinum-sensitive secondary recurrence permits the use of platinumbased chemotherapy and a further cytopenia surgery; the prognosis of these people is usually poor [9] In this scenario, the introduction of new targeted therapies changed the prognosis of patients with both platinum-sensitive and platinum-resistant recurrence. It is of important significance for the treatment of OC to elucidate the potential mechanism of action of OC process

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Conclusion