title: miR-21-3p is a positive regulator of L1CAM in several human carcinomas.
abstract: Expression of L1 cell adhesion molecule (L1CAM) 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. L1CAM promotes cell motility, invasion, chemoresistance and metastasis formation. Elucidating genetic processes involved in the expression of L1CAM in cancers is of considerable importance. Transcription factors such as SLUG, β-catenin/TCF-LEF, PAX8 and VHL have been implicated in the re-activation of L1CAM 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 L1CAM expression in renal, endometrial and ovarian carcinoma derived cell lines by an unknown mechanism involving transcriptional activation of the L1CAM gene. In patient cohorts from renal, endometrial and ovarian cancers we observed a strong positive correlation of L1CAM and miR-21-3p expressions. Although L1CAM alone was a reliable marker for overall and disease free survival, the combination of L1CAM and miR-21-3p expressions strongly enhanced the predictive power. Our findings shed new light on the complex regulation of L1CAM in cancers and advocate the use of L1CAM/miR-21-3p for diagnostic application.
authors.affiliation: Department of Translational Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Doberstein
authors.affiliation: Department of Translational Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Niko P
authors.initials: NP
authors.lastname: Bretz
authors.affiliation: Department of Translational Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Schirmer
authors.affiliation: Department of Urology, Goethe University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Heidi
authors.initials: H
authors.lastname: Fiegl
authors.affiliation: Department of Urology, Goethe University Hospital, D-60590 Frankfurt am Main, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Blaheta
authors.affiliation: Division Molecular Genome Analysis, German Cancer Research Center (DKFZ), D-69120 Heidelberg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Breunig
authors.affiliation: Department of Gynecology and Obstetrics, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Müller-Holzner
authors.affiliation: Department of Gynecology and Obstetrics, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
authors.forename: Dan
authors.initials: D
authors.lastname: Reimer
authors.affiliation: Department of Gynecology and Obstetrics, Medical University of Innsbruck, A-6020 Innsbruck, Austria.
authors.forename: Alain G
authors.initials: AG
authors.lastname: Zeimet
authors.affiliation: Department of Translational Immunology, German Cancer Research Center, D-69120 Heidelberg, Germany. Electronic address: P.Altevogt@dkfz.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Altevogt
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002277:Carcinoma / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D018572:Disease-Free Survival; D016889:Endometrial Neoplasms / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D039842:Neural Cell Adhesion Molecule L1 / Q000096:biosynthesis* / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D039842:Neural Cell Adhesion Molecule L1
keywords: Endometrial carcinoma; Kidney carcinoma; Ovarian carcinoma; miR-21-3