title: 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.
authors.affiliation: Department of Urology, Fuzhou General Hospital, Fujian Medical University, No.156, Xi'erhuan North Road, Fuzhou, 350025, China.
authors.forename: Tengyue
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Department of Urology, Lushan Sanatorium of the PLA, Lushan, 332000, China.
authors.forename: Libing
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Urology, Fuzhou General Hospital, Fujian Medical University, No.156, Xi'erhuan North Road, Fuzhou, 350025, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liao
authors.affiliation: Department of Urology, Fuzhou General Hospital, Fujian Medical University, No.156, Xi'erhuan North Road, Fuzhou, 350025, China.
authors.forename: Wenli
authors.initials: W
authors.lastname: Zhuo
authors.affiliation: Department of Urology, Fuzhou General Hospital, Fujian Medical University, No.156, Xi'erhuan North Road, Fuzhou, 350025, China.
authors.forename: Shunliang
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Urology, Fuzhou General Hospital, Fujian Medical University, No.156, Xi'erhuan North Road, Fuzhou, 350025, China.
authors.forename: Weizhen
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Urology, Fuzhou General Hospital, Fujian Medical University, No.156, Xi'erhuan North Road, Fuzhou, 350025, China. wangdongdr@sina.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D059565:G2 Phase Cell Cycle Checkpoints; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011762:Pyrroline Carboxylate Reductases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D011944:Receptors, Androgen / Q000378:metabolism; D015398:Signal Transduction; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase
chemical_list: D011762:Pyrroline Carboxylate Reductases; D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D000097502:delta-1-Pyrroline-5-Carboxylate Reductase; C410798:AR protein, human
keywords: AR signaling; Apoptosis; Cell cycle; Cell proliferation; PYCR1; Prostate cancer