miR-21-3p is a positive regulator of L1CAM in several human carcinomas

Expression of L1 cell adhesion molecule (L1 CAM) occurs frequently in human cancers and is associated with poor prognosis in cancers such as ovarian, endometrial, breast, renal cell carcinoma and pancreatic ductal adenocarcinoma. L1 CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1 CAM in cancers is of considerable importance. Transcription factors such as SLUG, beta-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1 CAM in various types of cancers. There is increasing evidence that micro-RNAs can also have strong effects on gene expression. Here we have identified miR-21-3p as a positive regulator of L1CAM expression. Over-expression of miR-21-3p (miR-21*) but not the complementary sequence miR-21-5p (miR-21) could strongly augment L1 CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1 CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1 CAM and miR-21-3p expressions. Although L1 CAM alone was a reliable marker for overall and disease free survival, the combination of L1 CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1 CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application. (C) 2014 Elsevier Ireland Ltd. All rights reserved.