The Prognostic Significance and Potential Mechanism of Prolyl 3-Hydroxylase 1 in Hepatocellular Carcinoma

Abstract

Background. Prolyl 3-hydroxylase 1 (P3H1) is essential for human collagen synthesis. Here, we investigated its relevance to multiple cancers, especially hepatocellular carcinoma (LIHC). Methods. We estimated the relationship of P3H1 with 33 cancers using publicly available databases. And immunohistochemistry was utilized to verify the P3H1 expression in liver, gastric, colon, pancreatic, and rectal cancer. Then, we attenuated P3H1 expression in BEL-7402 and HLF cells by lentivirus technology and assessed the effect of P3H1 on cell proliferation, migration, and invasion. Results. Bioinformatic analysis revealed a significantly higher expression of P3H1 in almost all tumors, which was consistent with the immunohistochemical findings in the liver, gastric, colon, pancreatic, and rectal cancers. P3H1 expression was associated with overall survival, progression-free interval, disease-specific survival, and disease-free interval in most cancers, particularly in LIHC. Besides, we also found that P3H1 expression was an independent prognostic factor for LIHC. And knockdown of P3H1 significantly reduced liver cancer cell proliferation, migration, and invasion in liver cancer cells. Interestingly, P3H1 expression levels showed a significant positive connection with Th2 infiltration through multiple immune infiltration algorithms. ICI treatment was less effective in LIHC patients with high P3H1 expression. Finally, we also identified an upstream regulatory mechanism of P3H1 in LIHC, namely, AL355488.1, HCG18, and THUMPD3-AS1/hsa-miR-29c-3p-P3H1 axis. Conclusion. We have systematically described for the first time that P3H1 is closely related to various tumors, particularly in LIHC, and interference with P3H1 may be a therapeutic target for patients with LIHC.

RETRACTED: Prognostic value and potential mechanism of cellular senescence and tumor microenvironment in hepatocellular carcinoma: Insights from bulk transcriptomics and single‐cell sequencing analysis

“…Previous literature has reported that PSMD14 can enhance the growth and metastasis of HCC by acting as a deubiquitinase to stabilize GRB2 23 . P3H1 was found to be upregulated in most tumors, and its knockdown significantly reduced the proliferation, migration, and invasion of HCC cells 24 . CENPA has also been reported to have predictive value in the development of HCC 25 .…”

“…23 P3H1 was found to be upregulated in most tumors, and its knockdown significantly reduced the proliferation, migration, and invasion of HCC cells. 24 CENPA has also been reported to have predictive value in the development of HCC. 25 G6PD has been shown to target cytochrome P450 reductase and inhibit ferroptosis in HCC.…”

A novel defined basement membrane-related genes signature for predicting the prognosis of Hepatocellular carcinoma

“…P3H1 expression levels may be used as an independent prognostic factor for patients with LIHC. Moreover, P3H1 knockdown greatly reduced the capacity of liver cancer cells to proliferate, migrate, and invade 40 .P3H1 expression levels may be used as a separate prognostic factor for patients with LIHC. Moreover, P3H1 knockdown greatly reduced the capacity of liver cancer cells to proliferate, migrate, and invade.…”

Downregulation of Bmal1 Expression in Celiac Ganglia Protects against Hepatic Ischemia-Reperfusion Injury

“…The lysates were then centrifuged at 12,000 rpm at 4 °C for minutes to remove debris, and the resulting supernatants were collected for electrophoresis. Western blotting was performed according to the protocol described in our previous study [ 26 ]. The primary antibodies used for the western blotting were TNF-α (Servicebio, China), IL-1β (Servicebio, China), and Tubulin-β (Abways Technology, Shanghai, China).…”