MicroRNA expression profiling of human metastatic cancers identifies cancer gene targets.
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.
Baffa
Raffaele
R
Department of Urology, Thomas Jefferson University, Kimmel Cancer Center, Philadelphia, PA, USA. R_Baffa@mail.jci.tju.edu
Fassan
Matteo
M
Volinia
Stefano
S
O'Hara
Brian
B
Liu
Chang-Gong
CG
Palazzo
Juan P
JP
Gardiman
Marina
M
Rugge
Massimo
M
Gomella
Leonard G
LG
Croce
Carlo M
CM
Rosenberg
Anne
A
D001943:Breast Neoplasms / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008207:Lymphatic Metastasis / Q000175:diagnosis / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D012334:RNA, Neoplasm / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000235:genetics
D035683:MicroRNAs; D012334:RNA, Neoplasm