miR-1247 is Correlated with Prognosis of Pancreatic Cancer and Inhibits Cell Proliferation by Targeting Neuropilins
S. Shi, Y. Lu, Y. Qin, W. Li, H. Cheng, Y. Xu, J. Xu, J. Long, L. Liu, C. Liu and X. Yu
Affiliation: (X. Yu) No. 270, Dong'An Road, Xuhui District, Shanghai, 200032, P.R. China.
Accumulating evidence indicates that microRNAs (miRNAs) have great potential as tumor
biomarkers and therapeutic agents owing to their functions in tumorigenesis and cancer progression. Aberrant
expression of miR-1247 has been found in several cancers and is predicted to play an important role in the
pathological processes of pancreatic cancer by miRNA-regulated network analysis. We investigated the
expression profile of miR-1247 in pancreatic cancer tissue microarray by in situ hybridization and found that
miR-1247 was significantly down-regulated in pancreatic cancer tissues compared to matched benign tissues.
High levels of miR-1247 expression were positively correlated with higher overall and recurrence free survival
in pancreatic cancer patients, while negatively correlated with tumor grade. Using in vitro and in vivo models,
we demonstrated that increased expression of miR-1247 inhibited proliferation, tumorigenicity, colony
formation and triggered G0/G1 cell cycle arrest in pancreatic cancer cells. Moreover, we confirmed that
neuropilin1 (NRP1) and neuropilin2 (NRP2) are direct targets of miR-1247 by western blot and luciferase
reporter assay. Further studies indicated that low dose all trans retinoic acid (ATRA) can induce
redifferentiation and restoration of miR-1247 in pancreatic cancer cells. These findings suggest that miR-1247,
a novel tumor suppressor, can act as a potential biomarker and therapeutic agent for pancreatic cancer.
Keywords: microRNA, neuropilin, pancreatic cancer, prognosis, retinoic acid, tumor grade.
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