Journal Article

MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL

Alexander Baraniskin, Karin Birkenkamp-Demtroder, Abdelouahid Maghnouj, Hannah Zöllner, Johanna Munding, Susanne Klein-Scory, Anke Reinacher-Schick, Irmgard Schwarte-Waldhoff, Wolff Schmiegel and Stephan A. Hahn

in Carcinogenesis

Volume 33, issue 4, pages 732-739
Published in print April 2012 | ISSN: 0143-3334
Published online January 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs020
MiR-30a-5p suppresses tumor growth in colon carcinoma by targeting DTL

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MicroRNAs (miRNAs) are small non-coding RNAs that are involved in different biological processes by suppressing target gene expression. Altered expression of miR-30a-5p has been reported in colon carcinoma. To elucidate its potential biological role in colon cancer, miR-30a-5p was overexpressed via a lentiviral vector system in two different colon cancer cell lines. This induced in both lines miR-30a-5p-mediated growth inhibition, attributable to a cell cycle arrest at the G1 phase and an induction of apoptosis. Combining global gene expression analyses of miR-30a-5p transgenic line HCT116 with in silico miRNA target prediction, we identified the denticleless protein homolog (DTL) as a potential miRNA-30a-5p target. Subsequent reporter gene assays confirmed the predicted miR-30a-5p binding site in the 3′untranslated region of DTL. Importantly, overexpression of DTL in HCT116 cells partially rescued these cells from miR-30a-5p-mediated growth suppression. In addition, TP53 and CDKN1A expression were increased in miR-30a-5p-overexpressing HCT116 cells, suggesting that miR-30a-5p is able to modulate the cell cycle via a DTL–TP53–CDKN1A regulatory circuit. Finally, 379 colorectal cancer tissues were screened for DTL expression and DTL was found to be overexpressed in 95.8% of human colorectal cancers compared with normal colon mucosa. In conclusion, our data identified miR-30a-5p as a tumor-suppressing miRNA in colon cancer cells exerting its function via modulation of DTL expression, which is frequently overexpressed in colorectal cancer. Thus, our data suggest that restoring miR-30a-5p function may prove useful as therapeutic strategy for tumors with reduced miR-30a-5p expression.

Journal Article.  6031 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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