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

Ning, Yue; Zheng, Hongmei; Zhan, Yuting; Liu, Sile; Yang, Yang; Zang, Hongjing; Wen, Qiuyuan; Zhang, Yajie; Fan, Songqing

doi:10.7150/jca.63147

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

Research Paper

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

Yue Ning^1,2, Hongmei Zheng¹, Yuting Zhan¹, Sile Liu¹, Yang Yang¹, Hongjing Zang¹, Qiuyuan Wen¹, Yajie Zhang^2✉, Songqing Fan^1✉

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.

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. https://www.jcancer.org/v12p6685.htm

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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

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APA

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

ACS

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.

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CSE

Ning Y, Zheng H, Zhan Y, Liu S, Yang Y, Zang H, Wen Q, Zhang Y, Fan S. 2021. Overexpression of P4HA1 associates with poor prognosis and promotes cell proliferation and metastasis of lung adenocarcinoma. J Cancer. 12(22):6685-6694.

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