J Cancer 2020; 11(10):2788-2799. doi:10.7150/jca.38401

Research Paper

P4HA2 contributes to cervical cancer progression via inducing epithelial-mesenchymal transition

Yuan Cao1*, Qicai Han2*, Juan Li2, Yanyan Jia1, Ruitao Zhang1, Huirong Shi1✉

1. Department of Gynaecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450014, China
2. Key Laboratory of Clinical Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Cao Y, Han Q, Li J, Jia Y, Zhang R, Shi H. P4HA2 contributes to cervical cancer progression via inducing epithelial-mesenchymal transition. J Cancer 2020; 11(10):2788-2799. doi:10.7150/jca.38401. Available from http://www.jcancer.org/v11p2788.htm

File import instruction

Abstract

Background: Cervical cancer is one of the most common gynaecological malignancies. Emerging studies have documented that prolyl-4-hydroxylase α subunit 2 (P4HA2) is involved in multiple processes of cancer progression. However, the functional roles of P4HA2 in cervical cancer progression remain to be elucidated.

Methods: P4HA2 mRNA and protein levels were examined in cervical cancer tissues and cell line by qRT-PCR and western blot. The correlation of the P4HA2 expression levels and prognosis of cervical cancer patients were analysed in TCGA cervical cancer cohort and tissue microarray (TMA) cohort. P4HA2 was silenced to evaluate its function on cervical cancer progression both in vitro and in vivo. Bioinformatics analysis was performed to investigate the underlying regulation mechanism of cervical cancer by P4HA2.

Results: We found that P4HA2 are markedly upregulated in cervical cancer tissues in comparison with adjacent non-neoplastic tissues. In addition, upregulation of P4HA2 was associated with shorter overall survival (OS) and relapse-free survival (RFS). Functionally, we demonstrated that P4HA2 knockdown attenuated cell proliferation, migration and invasion of cervical cancer cells. Furthermore, xenograft tumor mouse model experiment showed silencing P4HA2 significantly inhibited tumor growth in vivo. Mechanistically, bioinformatics analysis revealed that epithelial-mesenchymal transition (EMT) was involved in cervical cancer progression regulated by P4HA2 and we further confirmed knockdown P4HA2 suppressed the EMT process.

Conclusion: our results suggest that P4HA2 functions as an oncogene in promoting cervical cancer cell proliferation, migration and invasion by inducing EMT, which might be a promising prognostic factor and therapeutic target for cervical cancer.

Keywords: P4HA2, prognosis, metastasis, EMT, cervical cancer