Human antigen R mediated post-transcriptional regulation of inhibitors of apoptosis proteins in pancreatic cancer.
World J Gastroenterol
; 25(2): 205-219, 2019 Jan 14.
Article
de En
| MEDLINE
| ID: mdl-30670910
ABSTRACT
AIM:
To determine the association of human antigen R (HuR) and inhibitors of apoptosis proteins (IAP1, IAP2) and prognosis in pancreatic cancer.METHODS:
Protein and mRNA expression levels of IAP1, IAP2 and HuR in pancreatic ductal adenocarcinoma (PDAC) were compared with normal pancreatic tissue. The correlations among IAP1/IAP2 and HuR as well as their respective correlations with clinicopathological parameters were analyzed. The Kaplan-Meier method and log-rank tests were used for survival analysis. Immunoprecipitation assay was performed to demonstrate HuR binding to IAP1, IAP2 mRNA. PANC1 cells were transfected with either anti-HuR siRNA or control siRNA for 72 h and quantitative reverse transcription polymerase chain reaction (RT-PCR), western blot analysis was carried out.RESULTS:
RT-PCR analysis revealed that HuR, IAP1, IAP2 mRNA expression were accordingly 3.3-fold, 5.5-fold and 8.4 higher in the PDAC when compared to normal pancreas (P < 0.05). Expression of IAP1 was positively strongly correlated with HuR expression (P < 0.05, r = 0.783). Western blot analysis confirmed RT-PCR results. High IAP1 expression, tumor resection status, T stage, lymph-node metastases, tumor differentiation grade, perineural and lymphatic invasion were identified as significant factors for shorter survival in PDAC patients (P < 0.05). Immunohistological analysis showed that HuR was mainly expressed in the ductal cancer cell's nucleus and less so in cytoplasm. RNA immunoprecipitation analysis confirmed IAP1 and IAP2 post-transcriptional regulation by HuR protein. Following siHuR transfection, IAP1 mRNA and protein levels were decreased, however IAP2 expression levels were increased.CONCLUSION:
HuR mediated overexpression of IAP1 significantly correlates with poor outcomes and early progression of pancreatic cancer. Further studies are needed to assess the underlying mechanisms.Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Tumeurs du pancréas
/
Marqueurs biologiques tumoraux
/
Carcinome du canal pancréatique
/
Protéine-1 similaire à ELAV
/
Protéine-3 contenant des répétitions IAP baculovirales
Type d'étude:
Prognostic_studies
Limites:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Langue:
En
Journal:
World J Gastroenterol
Sujet du journal:
GASTROENTEROLOGIA
Année:
2019
Type de document:
Article
Pays d'affiliation:
Lituanie