Zheng X.,First Affiliated Hospital to the General Hospital of the PLA |
Cai S.,Chinese PLA General Hospital |
Huang Z.,Chinese PLA General Hospital
Molecular Medicine Reports | Year: 2015
MicroRNA (miRNA) is a type of short non-coding RNA that suppresses the expression of protein coding genes by partial complementary binding to the 3'-untranslated regions (UTRs) of mRNAs. miRNA expression alterations are involved in the initiation, progression and metastasis of human cancer and it has been suggested that miRNAs function as tumor suppressors as well as oncogenes in cancer development. PIM-3 is a member of the proto-oncogene PIM family, the aberrant expression of which exists in human pancreatic cancer tissues. There are reports indicating that overexpression of PIM3 is associated with the promotion of pancreatic cancer cell proliferation. The aim of the present study was to identify micro (mi)RNAs that regulate the expression of the oncogene PIM3 in PC. It was confirmed that the expression of PIM3 was regulated by miRNAs through an AGO2 knockout experiment. Subsequently, a dual luciferase assay system was constructed and used to screen 13 selected miRNAs that may target the PIM3 3'UTR directly. The results indicated that miR-15a/b, miR-16, miR-33a/b, miR-124, miR-195 and miR-506 repressed the luciferase activity by targeting the PIM3 3'UTR. However, only the expression of miR-506 was negatively correlated with PIM3 expression in PC tissues (r=0.38, P=0.017). Furthermore, a biological functional study indicated that miR-506 functioned as a tumor suppressor by repressing PC cell proliferation, which was partially reversed by PIM3 overexpression. To the best of our knowledge, the present study was the first to reveal the tumor suppressor function of miR-506 in PC, which has the potential to be employed in the diagnosis and treatment of PC.