MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets

• Published in: The Journal of pathology 2009-10, Vol.219 (2), p.214-221
• Main Authors: Baffa, Raffaele, Fassan, Matteo, Volinia, Stefano, O'Hara, Brian, Liu, Chang-Gong, Palazzo, Juan P, Gardiman, Marina, Rugge, Massimo, Gomella, Leonard G, Croce, Carlo M, Rosenberg, Anne
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Breast cancer; Breast Neoplasms - genetics; Colonic Neoplasms - genetics; expression signature; Female; Gene Expression Profiling - methods; Gene Expression Regulation, Neoplastic; gene target; Genes, Neoplasm; Humans; Investigative techniques, diagnostic techniques (general aspects); Lung Neoplasms - genetics; Lymphatic Metastasis - diagnosis; Lymphatic Metastasis - genetics; Medical sciences; metastatic cancers; MicroRNAs - genetics; miRNA; Oligonucleotide Array Sequence Analysis - methods; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; Reverse Transcriptase Polymerase Chain Reaction - methods; RNA, Neoplasm - genetics; Urinary Bladder Neoplasms - genetics
• ISSN: 0022-3417; 1096-9896
• DOI: 10.1002/path.2586

Small non-coding microRNAs (miRNAs) contribute to cancer development and progression, and are differentially expressed in normal tissues and cancers. However, the specific role of miRNAs in the metastatic process is still unknown. To seek a specific miRNA expression signature characterizing the metastatic phenotype of solid tumours, we performed a miRNA microarray analysis on 43 paired primary tumours (ten colon, ten bladder, 13 breast, and ten lung cancers) and one of their related metastatic lymph nodes. We identified a metastatic cancer miRNA signature comprising 15 overexpressed and 17 underexpressed miRNAs. Our results were confirmed by qRT-PCR analysis. Among the miRNAs identified, some have a well-characterized association with cancer progression, eg miR-10b, miR-21, miR-30a, miR-30e, miR-125b, miR-141, miR-200b, miR-200c, and miR-205. To further support our data, we performed an immunohistochemical analysis for three well-defined miRNA gene targets (PDCD4, DHFR, and HOXD10 genes) on a small series of paired colon, breast, and bladder cancers, and one of their metastatic lymph nodes. We found that the immunohistochemical expression of these targets significantly follows the corresponding miRNA deregulation. Our results suggest that specific miRNAs may be directly involved in cancer metastasis and that they may represent a novel diagnostic tool in the characterization of metastatic cancer gene targets. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley '' Sons, Ltd.