J Cancer 2021; 12(22):6685-6694. doi:10.7150/jca.63147 This issue

Research Paper

Overexpression of P4HA1 associates with poor prognosis and promotes cell proliferation and metastasis of lung adenocarcinoma

Yue Ning1,2, Hongmei Zheng1, Yuting Zhan1, Sile Liu1, Yang Yang1, Hongjing Zang1, Qiuyuan Wen1, Yajie Zhang2✉, Songqing Fan1✉

1. Department of Pathology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
2. Department of Pathology, School of Basic Medical Science, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China.

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Citation:
Ning Y, Zheng H, Zhan Y, Liu S, Yang Y, Zang H, Wen Q, Zhang Y, Fan S. Overexpression of P4HA1 associates with poor prognosis and promotes cell proliferation and metastasis of lung adenocarcinoma. J Cancer 2021; 12(22):6685-6694. doi:10.7150/jca.63147. Available from https://www.jcancer.org/v12p6685.htm

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Abstract

Graphic abstract

Prolyl 4-hydroxylase subunit alpha 1 (P4HA1) is the core active catalytic portion of prolyl 4-hydroxylase, and has contributed to tumorigenesis in several cancers. In this study, we identified that P4HA1 mRNA and protein are both up-regulated in non-small cell lung cancer (NSCLC). Besides, overexpressed P4HA1 is correlated with poor clinical outcomes and serve as an independent prognosis biomarker in lung adenocarcinoma (LUAD), but not lung squamous cell carcinoma (LUSC). In vitro studies, decreased P4HA1 significantly inhibits proliferation and cell cycle, by regulating cyclin-dependent kinases (CDKs), cyclins and CDK inhibitor (CKI). Moreover, via inhibiting epithelial-mesenchymal transition (EMT) and matrix metalloprotease (MMPs), dysregulation of P4HA1 could restrain the tumor cell invasion and metastasis of lung adenocarcinoma. In addition, we found that P4HA1 could enhance cell stemness and cisplatin-resistance in lung adenocarcinoma. In summary, P4HA1 plays a crucial role in the development of NSCLC and may provide a brand-new target for lung cancer treatment.

Keywords: P4HA1, non-small cell lung cancer, proliferation, metastasis, biomarker