The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.

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 r...

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Autores principales:	Joseph Mazar, Katherine DeYoung, Divya Khaitan, Edward Meister, Alvin Almodovar, James Goydos, Animesh Ray, Ranjan J Perera
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/17925ada051b4556b6789d7a93eae89a
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spelling	oai:doaj.org-article:17925ada051b4556b6789d7a93eae89a2021-11-18T07:02:36ZThe regulation of miRNA-211 expression and its role in melanoma cell invasiveness.1932-620310.1371/journal.pone.0013779https://doaj.org/article/17925ada051b4556b6789d7a93eae89a2010-11-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21072171/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The 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 3'-UTR abolished target cleavage. KCNMA1 mRNA and protein expression levels varied inversely with miR-211 levels. Two different melanoma cell lines ectopically expressing miR-211 exhibited significant growth inhibition and reduced invasiveness compared with the respective parental melanoma cell lines. An shRNA against KCNMA1 mRNA also demonstrated similar effects on melanoma cells. miR-211 is encoded within the sixth intron of TRPM1, a candidate suppressor of melanoma metastasis. The transcription factor MITF, important for melanocyte development and function, is needed for high TRPM1 expression. MITF is also needed for miR-211 expression, suggesting that the tumor-suppressor activities of MITF and/or TRPM1 may at least partially be due to miR-211's negative post transcriptional effects on the KCNMA1 transcript. Given previous reports of high KCNMA1 levels in metastasizing melanoma, prostate cancer and glioma, our findings that miR-211 is a direct posttranscriptional regulator of KCNMA1 expression as well as the dependence of this miRNA's expression on MITF activity, establishes miR-211 as an important regulatory agent in human melanoma.Joseph MazarKatherine DeYoungDivya KhaitanEdward MeisterAlvin AlmodovarJames GoydosAnimesh RayRanjan J PereraPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 11, p e13779 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Joseph Mazar Katherine DeYoung Divya Khaitan Edward Meister Alvin Almodovar James Goydos Animesh Ray Ranjan J Perera The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.
description	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 3'-UTR abolished target cleavage. KCNMA1 mRNA and protein expression levels varied inversely with miR-211 levels. Two different melanoma cell lines ectopically expressing miR-211 exhibited significant growth inhibition and reduced invasiveness compared with the respective parental melanoma cell lines. An shRNA against KCNMA1 mRNA also demonstrated similar effects on melanoma cells. miR-211 is encoded within the sixth intron of TRPM1, a candidate suppressor of melanoma metastasis. The transcription factor MITF, important for melanocyte development and function, is needed for high TRPM1 expression. MITF is also needed for miR-211 expression, suggesting that the tumor-suppressor activities of MITF and/or TRPM1 may at least partially be due to miR-211's negative post transcriptional effects on the KCNMA1 transcript. Given previous reports of high KCNMA1 levels in metastasizing melanoma, prostate cancer and glioma, our findings that miR-211 is a direct posttranscriptional regulator of KCNMA1 expression as well as the dependence of this miRNA's expression on MITF activity, establishes miR-211 as an important regulatory agent in human melanoma.
format	article
author	Joseph Mazar Katherine DeYoung Divya Khaitan Edward Meister Alvin Almodovar James Goydos Animesh Ray Ranjan J Perera
author_facet	Joseph Mazar Katherine DeYoung Divya Khaitan Edward Meister Alvin Almodovar James Goydos Animesh Ray Ranjan J Perera
author_sort	Joseph Mazar
title	The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.
title_short	The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.
title_full	The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.
title_fullStr	The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.
title_full_unstemmed	The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.
title_sort	regulation of mirna-211 expression and its role in melanoma cell invasiveness.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/17925ada051b4556b6789d7a93eae89a
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The regulation of miRNA-211 expression and its role in melanoma cell invasiveness.

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