Knockdown of PYCR1 inhibits cell proliferation and colony formation via cell cycle arrest and apoptosis in prostate cancer

Abstract

Pyrroline-5-carboxylate reductase 1 (PYCR1) is an enzyme involved in cell metabolism, which has been shown to be up-regulated in cancers. However, the functions of PYCR1 in prostate cancers (PCa) are still largely unknown. In the present study, we found that PYCR1 was highly expressed in prostate cancer tissues and then knocked down PYCR1 in PCa cell lines (DU145, PC-3 and LNCap) via lentivirus-mediated gene delivery and analyzed its biological function. Both qRT-PCR and western blotting indicated that PYCR1 was suppressed efficiently after sh-PYCR1 infection. Further analysis indicated knockdown of PYCR1 significantly inhibited PCa cell growth and colony formation ability. The inhibition effects on growth were likely due to G2/M-phase arrest and enhanced cell apoptosis, as determined by flow cytometer analysis. At last, we verified the expression levels of cell cycle regulatory proteins, including CDK1, CDK2, CDK4 and Cyclin B1 were all downregulated and cell apoptotic-related proteins, including cleaved caspase 3 and cleaved PARP were increased in PCa cells after PYCR1 knockdown. Furthermore, PYCR1 has been shown not to be directly regulated by androgen receptor (AR) levels. These results show the functions of PYCR1 in PCa tumorigenesis for the first time and suggest that PYCR1 might be a good potential therapy approach for treating PCa.

PYCR1 knockdown inhibits the proliferation, migration, and invasion by affecting JAK/STAT signaling pathway in lung adenocarcinoma

“…The results revealed that PYCR1 knockdown inhibited cell proliferation, migration, and invasion in LUAD cell lines. Through literature research, we found similar results, that is, PYCR1 knockdown gave rise to marked inhibition of various cancers, such as prostate tumor 24 and breast tumor 23 …”

“…The results revealed that PYCR1 knockdown inhibited cell proliferation, migration, and invasion in LUAD cell lines. Through literature research, we found similar results, that is, PYCR1 knockdown gave rise to marked inhibition of various cancers, such as prostate tumor 24 and breast tumor. 23 The JAK/STAT signaling pathway is a downstream pathway of cytokine signaling, which regulates cell differentiation, proliferation, and apoptosis and plays an important role in the occurrence and development of tumors.…”

“…22,23 Abnormal expression of PYCR1 plays an important role in tumor development and progression. It has been reported that PYCR1 knockdown inhibits cell proliferation and colony formation in prostate cancer, 24 and PYCR1 upregulation promotes proliferation and inhibits apoptosis in NSCLC. 25 Another research showed its antiapoptotic effect on breast cancer using coexpression network analysis.…”

Dynamics of the cell-free DNA methylome of metastatic prostate cancer during androgen-targeting treatment

“…The most common genes showing either increases or decreases in promoter methylation are in Supplementary Figure 6 , with certain genes implicated in PCa or other cancers. For instance, pyrroline-5-carboxylate reductase 1 ( PYCR1 ), which is involved in proline biosynthesis and can promote tumor cell growth (42), often demonstrated gain of methylation at visit C.…”

Quantitative Proteomic Analysis of Prostate Tissue Specimens Identifies Deregulated Protein Complexes in Primary Prostate Cancer

“…PYCR1 is a metabolic enzyme that catalyzes the NAD(P)H-dependent conversion of pyrroline-5-carboxylate to proline [46]. Previous studies showed that 1) compared with normal prostate, PYCR1 was significantly upregulated in PCa at both mRNA and protein levels, 2) the expression levels of PYCR1 were significantly associated with Gleason scores, and 3) PYCR1 is involved in PCa cell proliferation and colony formation [47,48]. MAMDC2 is a poorly characterized proteoglycan containing four MAM domains, which are commonly found in surface receptors [49].…”