miR-203 promotes proliferation, migration and invasion by degrading SIK1 in pancreatic cancer.

ABSTRACT

Pancreatic ductal adenocarcinoma (PDA) is among the most lethal human cancers and it is insensitive to many chemotherapeutic drugs. The molecular basis of pancreatic cancer remains to be elucidated. Investigations into the molecular mechanism involved in the development and progression as well as drug resistance of the disease may be useful to understand the pathogenesis and progression of the disease and offer new targets for effective therapies. In the present study, we showed that salt-inducible kinase 1 (SIK1) was downregulated and loss of SIK1 was associated with gemcitabine resistance in pancreatic cancer. In pancreatic cancer cells, SIK1 inhibited proliferation, migration and invasion. An analysis of potential microRNA target sites was performed using the prediction algorithms, miRanda, TargetScan and PicTar. The three algorithms predicted that miR-203 is capable of targeting 3'UTR of SIK1. Subsequent experiments confirmed the prediction. In addition, the results showed that miR-203 promotes proliferation, migration and invasion in pancreatic cancer cells, whereas the restoration of SIK1 abrogated the regulation of pre-miR­203-mediated proliferation, migration and invasion.