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.
journal_name
World J Gastroenteroljournal_title
World journal of gastroenterologyauthors
Lukosiute-Urboniene A,Jasukaitiene A,Silkuniene G,Barauskas V,Gulbinas A,Dambrauskas Zdoi
10.3748/wjg.v25.i2.205subject
Has Abstractpub_date
2019-01-14 00:00:00pages
205-219issue
2eissn
1007-9327issn
2219-2840journal_volume
25pub_type
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