PMID- 35654390
OWN - NLM
STAT- MEDLINE
DCOM- 20220823
LR  - 20220825
IS  - 1876-4320 (Electronic)
IS  - 1874-9399 (Linking)
VI  - 1865
IP  - 6
DP  - 2022 Aug
TI  - Epigenetic modification facilitates proline synthase PYCR1 aberrant expression in 
      gastric cancer.
PG  - 194829
LID - S1874-9399(22)00044-X [pii]
LID - 10.1016/j.bbagrm.2022.194829 [doi]
AB  - BACKGROUND & AIMS: Pyrroline-5-carboxylate reductase 1 (PYCR1) upregulation 
      contributes to the progression of gastric cancer (GC) and indicates poor 
      survival. However, PYCR1 expression profile in GC subtypes and the mechanism 
      behind its upregulation are not well-studied. METHODS: PYCR1 expression profiles 
      in GC subtypes and different stages of gastric carcinogenesis were assessed in 
      different GC cohorts. Genetic alterations and epigenetic modulation in PYCR1 
      regulation were further investigated using bioinformatics analysis and in vitro 
      experiments. RESULTS: PYCR1 expression was significantly higher in 
      intestinal-type GC and associated molecular subtypes in TCGA and ACRG GC cohorts. 
      During the cascade of intestinal-type GC, PYCR1 was continuously increased from 
      normal gastric tissues through to atrophic gastritis, to intraepithelial 
      neoplasia, and to GC. Copy number alterations in PYCR1 were associated with PYCR1 
      transcript expression. One CpG island was observed in PYCR1 promoter region, and 
      the hypomethylation occurred at this region could contribute to PYCR1 
      transcriptional activation in GC. Besides, H3K27ac combination was found in PYCR1 
      promoter, and acetyltransferase p300 induced H3K27ac could promote PYCR1 
      expression in GC. CONCLUSIONS: PYCR1 expression varies across GC subtypes, with 
      intestinal-type GC and associated molecular subtypes having the highest 
      expression. Hypomethylation at CpG sites and p300-induced H3K27ac modification 
      within PYCR1 promoter could contribute to maintaining PYCR1 overexpression in GC. 
      These results provide us with a new insight into epigenetic modulation in 
      mitochondrial proline metabolism.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Xiao, Shiyu
AU  - Xiao S
AD  - Department of Gastroenterology, Peking University Third Hospital, 49 North Garden 
      Road, Beijing, China; Beijing Key Laboratory of Helicobacter pylori Infection and 
      Upper Gastrointestinal Diseases, Peking University Third Hospital, 49 North 
      Garden Road, Beijing, China.
FAU - Yao, Xingyu
AU  - Yao X
AD  - Department of Gastroenterology, Peking University Third Hospital, 49 North Garden 
      Road, Beijing, China; Beijing Key Laboratory of Helicobacter pylori Infection and 
      Upper Gastrointestinal Diseases, Peking University Third Hospital, 49 North 
      Garden Road, Beijing, China.
FAU - Ye, Juxiang
AU  - Ye J
AD  - Department of Pathology, School of Basic Medical Science, Peking University Third 
      Hospital, Peking University Health Science Center, 49 North Garden Road, Beijing, 
      China.
FAU - Tian, Xueli
AU  - Tian X
AD  - Department of Gastroenterology, Peking University Third Hospital, 49 North Garden 
      Road, Beijing, China; Beijing Key Laboratory of Helicobacter pylori Infection and 
      Upper Gastrointestinal Diseases, Peking University Third Hospital, 49 North 
      Garden Road, Beijing, China.
FAU - Yin, Zhihao
AU  - Yin Z
AD  - Department of Gastroenterology, Peking University Third Hospital, 49 North Garden 
      Road, Beijing, China; Beijing Key Laboratory of Helicobacter pylori Infection and 
      Upper Gastrointestinal Diseases, Peking University Third Hospital, 49 North 
      Garden Road, Beijing, China.
FAU - Zhou, Liya
AU  - Zhou L
AD  - Department of Gastroenterology, Peking University Third Hospital, 49 North Garden 
      Road, Beijing, China; Beijing Key Laboratory of Helicobacter pylori Infection and 
      Upper Gastrointestinal Diseases, Peking University Third Hospital, 49 North 
      Garden Road, Beijing, China. Electronic address: zhouly_bjmu@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220530
PL  - Netherlands
TA  - Biochim Biophys Acta Gene Regul Mech
JT  - Biochimica et biophysica acta. Gene regulatory mechanisms
JID - 101731723
RN  - 9DLQ4CIU6V (Proline)
RN  - EC 1.5.1.- (Pyrroline Carboxylate Reductases)
SB  - IM
MH  - CpG Islands/genetics
MH  - Epigenesis, Genetic
MH  - Humans
MH  - Proline/genetics/metabolism
MH  - Pyrroline Carboxylate Reductases/genetics/metabolism
MH  - *Stomach Neoplasms/genetics
OTO - NOTNLM
OT  - Gastric cancer
OT  - Histone acetylation
OT  - Methylation
OT  - PYCR1
OT  - Proline metabolism
EDAT- 2022/06/03 06:00
MHDA- 2022/08/24 06:00
CRDT- 2022/06/02 19:28
PHST- 2021/11/12 00:00 [received]
PHST- 2022/05/17 00:00 [revised]
PHST- 2022/05/23 00:00 [accepted]
PHST- 2022/06/03 06:00 [pubmed]
PHST- 2022/08/24 06:00 [medline]
PHST- 2022/06/02 19:28 [entrez]
AID - S1874-9399(22)00044-X [pii]
AID - 10.1016/j.bbagrm.2022.194829 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Gene Regul Mech. 2022 Aug;1865(6):194829. doi: 
      10.1016/j.bbagrm.2022.194829. Epub 2022 May 30.