RGD Reference Report - Calreticulin regulates vascular endothelial growth factor-A mRNA stability in gastric cancer cells. - Rat Genome Database

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Calreticulin regulates vascular endothelial growth factor-A mRNA stability in gastric cancer cells.

Authors: Lee, Po-Chu  Chiang, Jui-Chung  Chen, Chih-Yu  Chien, Yin-Chieh  Chen, Wei-Min  Huang, Chin-Wei  Weng, Wen-Chin  Chen, Chia-I  Lee, Po-Huang  Chen, Chiung-Nien  Lee, Hsinyu 
Citation: Lee PC, etal., PLoS One. 2019 Nov 14;14(11):e0225107. doi: 10.1371/journal.pone.0225107. eCollection 2019.
RGD ID: 150521680
Pubmed: PMID:31725767   (View Abstract at PubMed)
PMCID: PMC6855450   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0225107   (Journal Full-text)

Calreticulin (CRT) and vascular endothelial growth factor-A (VEGF-A) are crucial for angiogenesis, and mediate multiple malignant behaviors in gastric cancer. In this study, we report that CRT is positively correlated with VEGF-A in gastric cancer patients. Moreover, high expressions of both CRT and VEGF-A are markedly associated with the pathological stage, progression, and poor prognosis in the patients. Therefore, we sought to elucidate the mechanism by which CRT affects VEGF-A in gastric cancer. Firstly, we demonstrate the novel finding that knockdown of CRT reduced VEGF-A mRNA stability in two gastric cancer cell lines, AGS and MKN45. The AU-Rich element (ARE) is believed to play a crucial role in the maintenance of VEGF-A mRNA stability. Luciferase reporter assay shows that knockdown of CRT significantly decreased the activity of renilla luciferase with VEGF-A ARE sequence. Additionally, competition results from RNA-binding/electrophoretic mobility shift assay indicate that CRT forms an RNA-protein complex with the VEGF-A mRNA by binding to the ARE. In addition, the proliferation rate of human umbilical vein endothelial cells (HUVEC) was significantly reduced when treated with conditioned medium from CRT knockdown cells; this was rescued by exogenous VEGF-A recombinant protein. Our results demonstrate that CRT is involved in VEGF-A ARE binding protein complexes to stabilize VEGF-A mRNA, thereby promoting the angiogenesis, and progression of gastric cancer.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
stomach cancer disease_progressionIEP 150521680protein:increased expression:stomach (human)RGD 
stomach cancer disease_progressionISOCALR (Homo sapiens)150521680; 150521680protein:increased expression:stomach (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Calr  (calreticulin)

Genes (Mus musculus)
Calr  (calreticulin)

Genes (Homo sapiens)
CALR  (calreticulin)


Additional Information