Microrna-106b-25 cluster expression is associated with early disease recurrence and targets caspase-7 and focal adhesion in human prostate cancer

ABSTRACT The _miR-106b-25_ microRNA (miRNA) cluster is a candidate oncogene in human prostate cancer. Here, we report that miRNAs encoded by _miR-106b-25_ are upregulated in both primary

tumors and distant metastasis. Moreover, increased tumor _miR-106b_ expression was associated with disease recurrence and the combination of high _miR-106b_ and low _CASP7_ (caspase-7)

expressions in primary tumors was an independent predictor of early disease recurrence (adjusted hazard ratio=4.1; 95% confidence interval: 1.6–12.3). To identify yet unknown oncogenic

functions of _miR-106b_, we overexpressed it in LNCaP human prostate cancer cells to examine _miR-106b_-induced global expression changes among protein-coding genes. The approach revealed

that _CASP7_ is a direct target of _miR-106b_, which was confirmed by western blot analysis and a 3′-untranslated region reporter assay. Moreover, selected phenotypes induced by _miR-106b_

knockdown in DU145 human prostate cancer cells did not develop when both _miR-106b_ and _CASP7_ expression were inhibited. Further analyses showed that _CASP7_ is downregulated in primary

prostate tumors and metastatic lesions across multiple data sets and is by itself associated with disease recurrence and disease-specific survival. Using bioinformatics, we also observed

that _miR-106b-25_ may specifically influence focal adhesion-related pathways. This observation was experimentally examined using _miR-106b-25_-transduced 22Rv1 human prostate cancer cells.

After infection with a _miR-106b-25_ lentiviral expression construct, 22Rv1 cells showed increased adhesion to basement membrane- and bone matrix-related filaments and enhanced soft agar

growth. In summary, _miR-106b-25_ was found to be associated with prostate cancer progression and disease outcome and may do so by altering apoptosis- and focal adhesion-related pathways.

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support SIMILAR CONTENT BEING VIEWED BY OTHERS THE MICRORNA-3622 FAMILY AT THE 8P21 LOCUS EXERTS ONCOGENIC EFFECTS BY REGULATING THE P53-DOWNSTREAM GENE NETWORK IN PROSTATE CANCER

PROGRESSION Article 02 May 2022 CIRC_0001671 REGULATES PROSTATE CANCER PROGRESSION THROUGH MIR-27B-3P/BLM AXIS Article Open access 28 May 2024 MIRNA-671-5P PROMOTES PROSTATE CANCER

DEVELOPMENT AND METASTASIS BY TARGETING NFIA/CRYAB AXIS Article Open access 03 November 2020 ACCESSION CODES ACCESSIONS GENE EXPRESSION OMNIBUS * GSE34893 ABBREVIATIONS * miR: microRNA *

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Laboratory for technical help. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. AUTHOR INFORMATION AUTHORS

AND AFFILIATIONS * Laboratory of Human Carcinogenesis, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health, Bethesda, MD, USA R S Hudson, S A

Glynn, A M Starks, Y Yang, A J Schetter, T H Dorsey & S Ambs * Advanced Biomedical Computing Center, SAIC-Frederick, Inc., NCI, Frederick, MD, USA M Yi & R M Stephens * Protein

Expression Laboratory, Advanced Technology Program, SAIC-Frederick, Inc., NCI, Frederick, MD, USA D Esposito * Laboratory of Molecular Immunoregulation, NCI-Frederick, Frederick, MD, USA S K

Watkins & A A Hurwitz * Department of Molecular Virology, Immunology and Medical Genetics, Comprehensive Cancer Center, Ohio State University, Columbus, OH, USA C M Croce Authors * R S

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* A M Starks View author publications You can also search for this author inPubMed Google Scholar * Y Yang View author publications You can also search for this author inPubMed Google

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DECLARATIONS COMPETING INTERESTS The authors declare no conflict of interest. ADDITIONAL INFORMATION Supplementary Information accompanies the paper on the Oncogene website SUPPLEMENTARY

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CITE THIS ARTICLE Hudson, R., Yi, M., Esposito, D. _et al._ MicroRNA-106b-25 cluster expression is associated with early disease recurrence and targets caspase-7 and focal adhesion in human

prostate cancer. _Oncogene_ 32, 4139–4147 (2013). https://doi.org/10.1038/onc.2012.424 Download citation * Received: 09 February 2012 * Revised: 20 July 2012 * Accepted: 02 August 2012 *

Published: 17 September 2012 * Issue Date: 29 August 2013 * DOI: https://doi.org/10.1038/onc.2012.424 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this

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KEYWORDS * prostate cancer * microRNA * apoptosis * disease outcome