Collagen prolyl 4-hydroxylase 2 predicts worse prognosis and promotes glycolysis in cervical cancer

Qingxian Li; Qingying Wang; Qinyi Zhang; Jing Zhang; Jiawen Zhang

Collagen prolyl 4-hydroxylase 2 predicts worse prognosis and promotes glycolysis in cervical cancer

Am J Transl Res. 2019 Nov 15;11(11):6938-6951. eCollection 2019.

Authors

Qingxian Li¹, Qingying Wang², Qinyi Zhang³, Jing Zhang^{4

5}, Jiawen Zhang²

Affiliations

¹ Department of Gynaecology and Obstetrics, Putuo Hospital, Shanghai University of Traditional Chinese Medicine Shanghai, China.
² Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai, China.
³ Department of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University Shanghai, China.
⁴ Department of Integrated Therapy, Shanghai Cancer Center, Fudan University Shanghai, China.
⁵ Department of Oncology, Shanghai Medical College, Fudan University Shanghai, China.

PMID: 31814898
PMCID: PMC6895525

Abstract

P4HA2 is one of collagen prolyl 4-hydroxylase (P4H) isoform and increased in several types of human cancer. However, the role of P4HA2 during cervical tumorigenesis remains largely unknown. Here, we report that the protein level of P4HA2 is significantly increased in cervical cancer tissues. Silencing of P4HA2 inhibits cervical cancer cell proliferation, colony formation and migration. We also demonstrate decreased glucose uptake and lactate production in P4HA2 knockdown cells. Mechanistically, P4HA2 promotes cervical cancer cell glycolysis through upregulation of PGK1 and LDHA. We find a positive correlation between P4HA2 and PGK1/LDHA expression in cervical cancer tissues. Importantly, high expression of P4HA2, PGK1 or LDHA has a significantly shorter overall survival period and the survival prediction is enhanced by using combination of P4HA2 and PGK1/LDHA expression. Collectively, we identify P4HA2 as a regulator of glycolysis through PGK1 and LDHA, which may serve as a potential therapeutic target for cervical cancer.

Keywords: LDHA; P4HA2; PGK1; cervical cancer; glycolysis.