Loss of tumor suppressor mir-203 mediates overexpression of LIM and SH3 Protein 1 (LASP1) in high-risk prostate cancer thereby increasing cell proliferation and migration
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Amelie Hailer1,*, Thomas GP Grunewald2,*, Martin Orth1, Cora Reiss1, Burkhard Kneitz3, Martin Spahn3 and Elke Butt1
1 Institute for Clinical Biochemistry and Pathobiochemistry, University Clinic of Wuerzburg, Grombuehlstrasse 12, 97080 Wuerzburg, Germany
2 INSERM Unit 830, Genetics and Biology of Cancers, Institute Curie Research Center, 26 rue d’Ulm, 75248 Paris, France
3 Urology and Pediatric Urology, University Clinic of Wuerzburg, Oberduerrbacher Strasse 6, 97080 Wuerzburg, Germany
* These authors contributed equally to this work
Elke Butt, email:
Keywords: LASP1, prostate cancer, mir-203, PSA, LNCaP
Received: March 18, 2014 Accepted: April 25, 2014 Published: April 27, 2014
Several studies have linked overexpression of the LIM and SH3 domain protein 1 (LASP1) to progression of breast, colon, liver, and bladder cancer. However, its expression pattern and role in human prostate cancer (PCa) remained largely undefined.
Analysis of published microarray data revealed a significant overexpression of LASP1 in PCa metastases compared to parental primary tumors and normal prostate epithelial cells. Subsequent gene-set enrichment analysis comparing LASP1-high and -low PCa identified an association of LASP1 with genes involved in locomotory behavior and chemokine signaling. These bioinformatic predictions were confirmed in vitro as the inducible short hairpin RNA-mediated LASP1 knockdown impaired migration and proliferation in LNCaP prostate cancer cells.
By immunohistochemical staining and semi-quantitative image analysis of whole tissue sections we found an enhanced expression of LASP1 in primary PCa and lymph node metastases over benign prostatic hyperplasia. Strong cytosolic and nuclear LASP1 immunoreactivity correlated with PSA progression. Conversely, qRT-PCR analyses for mir-203, which is a known translational suppressor of LASP1 in matched RNA samples revealed an inverse correlation of LASP1 protein and mir-203 expression. Collectively, our results suggest that loss of mir-203 expression and thus uncontrolled LASP1 overexpression might drive progression of PCa.
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