Role Of Long Noncoding RNA Uc.345 In Pancreatic Ductal Adenocarcinoma

Objective: To identify the expression of long noncoding RNA(lncRNA)in pancreatic ductal adenocarcinoma.Analysis of uc.345 expression in pancreatic ductal adenocarcinoma tissue and its correlation with overall survival.Determine the effect of uc.345 in pancreatic cancer cell biology function and further explore the possibly molecular mechanism of pancreatic tumorigenesis.Methods: We used lncRNA microarrays to identify the expression of lncRNA in pancreatic ductal adenocarcinoma tissues and paired adjacent normal tissues.Statistical analyzed uc.345 expression in pancreatic cancer tissues and its correlation with overall survival.For research the pancreatic cancer biological function,we used qRT-PCR to pick up uc.345 low/high expression pancreatic cancer cells.Then,we used retrovirus packed uc.345 plasimid to overexpress uc.345 in pancreatic cancer cell lines to evaluate the tumor formation ability in vitro or vivo by colony formation assay and subcutaneous tumor growth ability in nude mice.The impact of uc.345 to pancreatic cancer stem cells by flow cytometry(FCM)was checked.For further study the molecular mechanism of uc.345 in pancreatic tumorigenesis,LC-MS/MS was used to evaluate the proteins expression when uc.345 upregulation in pancreatic cancer cells.Based on protein spectrum analysis,we used retrovirus shRNA to knock down hnRNP L and determined the relationship between uc.345 and hnRNP L by qRT-PCR,western blotting and colony formation assay.Results: lncRNA microarrays identified 2506 lncRNA and 2154 mRNA aberrant expression in pancreatic carcinoma tissues and paired adjacent normal tissues.uc.345 was up-regulated in tumor tissues compared to the paired adjacent normal tissues in 103 pairs pancreatic carcer tissues.The high level of uc.345 expression predicted a poor prognosis.Overexpression uc.345 in PANC-1 and Patu8988 cell lines enhanced the cloning forming ability in vitro,subcutaneous tumor growth ability in nude mice and increased pancreatic cancer stem cell numbers.Protein spectrum analysis confirmed that hnRNP L was uc.345 downstream related protein and knocked down hnRNP L could repress the pancreatic tumor formation ability which was promoted by uc.345.Conclusion: lncRNA microarrays could identify lncRNA and mRNA aberrant expression in pancreatic cancer and uc.345 plays an important role in pancreatic cancer.The high level of uc.345 expression in pancreatic cancer patients predicted a poor overall survival.uc.345 could promote pancreatic tumorigenesis and increase pancreatic cancer stem cell property.uc.345 promoted pancreatic tumorigenesis depended on hnRNP L.In conclusion,uc.345 is closely associated with the occurrence and development of pancreatic cancer and could be a potential prognostic and therapeutic target of pancreatic cancer.