PMID- 32953737
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220417
IS  - 2305-5839 (Print)
IS  - 2305-5847 (Electronic)
IS  - 2305-5839 (Linking)
VI  - 8
IP  - 15
DP  - 2020 Aug
TI  - Pyrroline-5-carboxylate reductase 1 (PYCR1) upregulation contributes to gastric 
      cancer progression and indicates poor survival outcome.
PG  - 937
LID - 10.21037/atm-19-4402 [doi]
LID - 937
AB  - BACKGROUND: Proline levels are significantly increased in tumor specimens and 
      urine samples from gastric cancer (GC) patients, and we previously showed that 
      intracellular proline levels significantly differ between human GC cell lines and 
      normal gastric epithelial cells. Pyrroline-5-carboxylate reductase 1 (PYCR1) is 
      the key enzyme in intracellular proline synthesis, but its role in GC remains 
      largely unknown. METHODS: Bioinformatic analysis and immunohistochemical (IHC) 
      staining with a tissue microarray were conducted to assess the association 
      between PYCR1 expression and clinical parameters. PYCR1 downregulation and 
      overexpression were then established in two GC cell lines (AGS and MKN28 cells) 
      to determine whether PYCR1 promotes malignant behavior in GC. Gene set enrichment 
      analysis (GSEA) was further performed to investigate the pathway regulating PYCR1 
      in GC. RESULTS: PYCR1 expression was up-regulated in different GC cohorts. High 
      PYCR1 protein expression was correlated with advanced tumor stage, aggressive 
      histological type and high Ki-67 index. High PYCR1 expression in GC tissues was 
      an indicator of poor outcome in GC patients. In vitro, PYCR1 knockdown markedly 
      attenuated GC cells growth and promoted apoptosis, while overexpression produced 
      the opposite effects. GSEA analysis indicated PI3K/Akt axis was strongly 
      correlated with PYCR1 expression and that PIK3CB and AKT1 mRNA expression was 
      positively associated with PYCR1 in GC tissues. PI3K inhibition further 
      significantly reduced PYCR1 mRNA and protein expression. Moreover, as PYCR1 is a 
      mitochondrial endomembrane protein, nutrient stress induced by glucose 
      deprivation also regulated PYCR1 expression. CONCLUSIONS: PYCR1 is highly 
      expressed in GC and acts as a mitochondrial oncogene to induce cancer progression 
      by enhancing tumor proliferation and responding to metabolic stress. PYCR1 is a 
      novel prognostic marker and a potential therapeutic target in GC.
CI  - 2020 Annals of Translational Medicine. All rights reserved.
FAU - Xiao, Shiyu
AU  - Xiao S
AD  - Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
AD  - Beijing Key Laboratory of Helicobacter pylori Infection and Upper 
      Gastrointestinal Diseases, Peking University Third Hospital, Beijing, China.
FAU - Li, Sizhu
AU  - Li S
AD  - Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
AD  - Beijing Key Laboratory of Helicobacter pylori Infection and Upper 
      Gastrointestinal Diseases, Peking University Third Hospital, Beijing, China.
FAU - Yuan, Ziying
AU  - Yuan Z
AD  - Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
AD  - Beijing Key Laboratory of Helicobacter pylori Infection and Upper 
      Gastrointestinal Diseases, Peking University Third Hospital, Beijing, China.
FAU - Zhou, Liya
AU  - Zhou L
AD  - Department of Gastroenterology, Peking University Third Hospital, Beijing, China.
AD  - Beijing Key Laboratory of Helicobacter pylori Infection and Upper 
      Gastrointestinal Diseases, Peking University Third Hospital, Beijing, China.
LA  - eng
PT  - Journal Article
PL  - China
TA  - Ann Transl Med
JT  - Annals of translational medicine
JID - 101617978
PMC - PMC7475402
OTO - NOTNLM
OT  - Gastric cancer (GC)
OT  - PI3K/Akt
OT  - Pyrroline-5-carboxylate reductase 1 (PYCR1)
OT  - metabolic stress
OT  - proline metabolism
COIS- Conflicts of Interest: All authors have completed the ICMJE uniform disclosure 
      form (available at http://dx.doi.org/10.21037/atm-19-4402). The authors have no 
      conflicts of interest to declare.
EDAT- 2020/09/22 06:00
MHDA- 2020/09/22 06:01
PMCR- 2020/08/01
CRDT- 2020/09/21 06:17
PHST- 2020/09/21 06:17 [entrez]
PHST- 2020/09/22 06:00 [pubmed]
PHST- 2020/09/22 06:01 [medline]
PHST- 2020/08/01 00:00 [pmc-release]
AID - atm-08-15-937 [pii]
AID - 10.21037/atm-19-4402 [doi]
PST - ppublish
SO  - Ann Transl Med. 2020 Aug;8(15):937. doi: 10.21037/atm-19-4402.