P4HA2

Official Full Name

prolyl 4-hydroxylase subunit alpha 2

Organism

Homo sapiens

GeneID

8974

Background

This gene encodes a component of prolyl 4-hydroxylase, a key enzyme in collagen synthesis composed of two identical alpha subunits and two beta subunits. The encoded protein is one of several different types of alpha subunits and provides the major part of the catalytic site of the active enzyme. In collagen and related proteins, prolyl 4-hydroxylase catalyzes the formation of 4-hydroxyproline that is essential to the proper three-dimensional folding of newly synthesized procollagen chains. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

Synonyms

MYP25; lncRNA-PE;

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Detailed Information

Epithelial-mesenchymal transition induced by P4HA2 contributes to cervical cancer progression

Prolyl-4-hydroxylase α subunit 2 (P4HA2) is documented by emerging studies to be involved in multiple processes of cancers, which included the most common gynecological malignancies, cervical cancer. In comparison with adjacent non-neoplastic tissues, markedly upregulation of P4HA2 was found in cervical cancer, more than this, association with shorter overall survival (OS) and relapse-free survival (RFS) have been partially accounted for this. Knockdown of P4HA2 has been demonstrated to be capable of delivering attenuation for the proliferation, migration and invasion of cervical cancer cells. P4HA2 silencing in xenograft tumor mouse model can significantly inhibit tumor growth. Involvement of epithelial-mesenchymal transition (EMT) regulated by P4HA2 in cervical cancer progression revealed by bioinformatics analysis may be its partial mechanism. Epithelial cells are transcriptionally reprogrammed to mesenchymal-like phenotype in the epithelial-mesenchymal transition (EMT) process, which is demonstrated to be closely involved in collagen biosynthesis and deposition of the cancer progression. And it is partially responsible for the highly metastatic behavior and aggressive nature of cancers. Oncogene functionality of P4HA2 in promoting cervical cancer cell proliferation, migration and invasion by inducing EMT hint it might be a promising prognostic factor and therapeutic target for cervical cancer.

P4HA2 acts as a promoter of EMT via collagen regulation and PI3K/AKT pathway

In P4HA2 knockdown experiment in the glioma cells in vitro or tumor xenograft mice model in vivo, bioinformatics analysis demonstrated that PI3K/AKT is the most enriched pathways of the co-expressed genes with P4HA2. In addition to this, mRNA expression of a series of collagen genes was found to be positively correlated with P4HA2 mRNA, while not mRNA expression of PI3K or AKT1/2. Inhibition on the migration, invasion and EMT-related molecules induced by P4HA2 knockdown can be reproduced by Akt phosphorylation activator. Series of collagens, type I, III, IV, VI and XVI, working as the major frame component of ECM was revealed to be upregulated in glioma, and it may be an indication that they are involved with the glioma genesis. Interaction of the collagen with binding receptors of ECM-cell may serve as signaling transduction. In consideration of P4HA2-collagen-PI3K/AKT pathway in glioma progression, RNA interference or P4HA2 targeted enzymatic inhibitors can be developed as a therapeutic strategy in the treatment of GBM.

Figure 1. The mighty molecular mechanism of P4HA2 and Carabin in regulating B-cell Lymphoma progression. (Ren Xu, et al. 2010)

References:

Jiang W, Zhou X, Li Z, et al. Prolyl 4-hydroxylase 2 promotes B-cell lymphoma progression via hydroxylation of Carabin. Blood, The Journal of the American Society of Hematology, 2018, 131(12): 1325-1336.
Cao Y, Han Q, Li J, et al. P4HA2 contributes to cervical cancer progression via inducing epithelial-mesenchymal transition. Journal of Cancer, 2020, 11(10): 2788.
Shi R, Gao S, Zhang J, et al. Collagen prolyl 4-hydroxylases modify tumor progression. Acta Biochimica et Biophysica Sinica, 2021.

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