the regulation of mirna-211 expression and its role in melanoma cell invasivenessmicrorna的表达- 211的规定及其在黑色素瘤细胞侵袭性作用.pdfVIP

The Regulation of miRNA-211 Expression and Its Role in Melanoma Cell Invasiveness 1 2 1 2 1 Joseph Mazar , Katherine DeYoung , Divya Khaitan , Edward Meister , Alvin Almodovar , James 3 4 1,2 Goydos , Animesh Ray , Ranjan J. Perera * 1 Sanford Burnham Medical Research Institute, Orlando, Florida, United States of America, 2 Curtis and Elizabeth Anderson Cancer Institute, Savannah, Georgia, United States of America, 3 Robert Wood Johnson Medical School, Cancer Institute of New Jersey, New Brunswick, New Jersey, United States of America, 4 Keck Graduate Institute, Claremont, California, United States of America Abstract The immediate molecular mechanisms behind invasive melanoma are poorly understood. Recent studies implicate microRNAs (miRNAs) as important agents in melanoma and other cancers. To investigate the role of miRNAs in melanoma, we subjected human melanoma cell lines to miRNA expression profiling, and report a range of variations in several miRNAs. Specifically, compared with expression levels in melanocytes, levels of miR-211 were consistently reduced in all eight non- pigmented melanoma cell lines we examined; they were also reduced in 21 out of 30 distinct melanoma samples from patients, classified as primary in situ, regional metastatic, distant metastatic, and nodal metastatic. The levels of several predicted target mRNAs of miR-211 were reduced in melanoma cell lines that ectopically expressed miR-211. In vivo target cleavage assays confirmed one such target mRNA encoded by KCNMA1. Mutating the miR-211 binding site seed sequences at the KCNMA1 39-UTR abolished targe