MicroRNA-21 Regulates the Invasion and Metastasis inCholangiocarcinoma and May Be a Potential Biomarker forCancer Prognosis


Background: MicroRNAs are noncoding RNA molecules that posttranscriptionally regulate gene expression.The aim of this study was to determine the role of microRNA-21 in cholangiocarcinomas and its relationshipto cholangiocarcinoma RBE cell capacity for invasion and metastasis.
Methods: MicroRNA-21 expression wasinvestigated in 41 cases of cholangiocarcinoma samples by in situ hybridization and real-time PCR. Influenceon cholangiocarcinoma cell line invasion and metastasis was analyzed with microRNA-21 transfected cells. Inaddition, regulation of reversion-inducing-cysteine-rich protein with kazal motifs (RECK) by microRNA-21was elucidated to identify mechanisms.
Results: In situ hybridization and real-time quantitative PCR resultsfor patients with lymph node metastasis or perineural invasion showed significantly high expression ofmicroRNA-21 (P<0.05). There was a dramatic decrease in cholangiocarcinoma cell line invasion and metastasisability after microRNA-21 knockdown (P<0.05). However, overexpression significantly increased invasion andmetastasis (P<0.05). Real-time PCR and Western-blot analysis showed that microRNA-21 could potentiallyinhibit RECK expression in RBE cells. Survival analysis showed that patients with higher expression levels ofmicroRNA-21 more often had a poor prognosis (P<0.05).
Conclusions: MicroRNA-21 may play an importantrole in cholangiocarcinoma invasion and metastasis, suggesting that MicroRNA-21 should be further evaluatedas a biomarker for predicting cholangiocarcinoma prognosis.