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Am J Pathol
2012 May 01;1805:1772-80. doi: 10.1016/j.ajpath.2012.01.008.
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MicroRNA 96 is a post-transcriptional suppressor of anaplastic lymphoma kinase expression.
Vishwamitra D
,
Li Y
,
Wilson D
,
Manshouri R
,
Curry CV
,
Shi B
,
Tang XM
,
Sheehan AM
,
Wistuba II
,
Shi P
,
Amin HM
.
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Anaplastic lymphoma kinase (ALK) constitutes a part of the oncogenic fusion proteins nucleophosmin-ALK and echinoderm microtubule-associated protein like 4-ALK, which are aberrantly expressed in a subset of T-cell anaplastic large-cell lymphoma and non-small-cell lung cancer, respectively. The expression of mutated, constitutively active ALK also occurs in a subset of neuroblastoma tumors. ALK is believed to play an important role in promoting tumor survival. Nevertheless, the mechanisms underlying the expression of ALK in cancer cells are not completely known. MicroRNA (miR) has been implicated in the regulation of the expression of both oncogenes and tumor suppressor genes. We tested the hypothesis that the expression of ALK could be regulated by miR. Three Internet-based algorithms identified miR-96 to potentially bind with the ALK 3'-untranslated region. Notably, miR-96 levels were markedly decreased in ALK-expressing cancer cell lines and primary human tumors compared with their normal cellular and tissue counterparts. Transfection of the cell lines with miR-96 decreased levels of the different forms of ALK protein, without significant effects on ALK mRNA. Furthermore, miR-96 decreased the phosphorylation of ALK target proteins, including Akt, STAT3, JNK, and type I insulin-like growth factor receptor, and it down-regulated JunB. These effects were associated with reduced proliferation, colony formation, and migration of ALK-expressing cancer cells. These data provide novel evidence that decreases in miR-96 could represent a mechanism underlying the aberrant expression of ALK in cancer cells.
Amin,
Pathobiology of ALK+ anaplastic large-cell lymphoma.
2007, Pubmed
Amin,
Pathobiology of ALK+ anaplastic large-cell lymphoma.
2007,
Pubmed
Bader,
The promise of microRNA replacement therapy.
2010,
Pubmed
Bai,
Nucleophosmin-anaplastic lymphoma kinase associated with anaplastic large-cell lymphoma activates the phosphatidylinositol 3-kinase/Akt antiapoptotic signaling pathway.
2000,
Pubmed
Bueno,
Genetic and epigenetic silencing of microRNA-203 enhances ABL1 and BCR-ABL1 oncogene expression.
2008,
Pubmed
Butrynski,
Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor.
2010,
Pubmed
Calin,
MicroRNA signatures in human cancers.
2006,
Pubmed
Chen,
Oncogenic mutations of ALK kinase in neuroblastoma.
2008,
Pubmed
Chiarle,
The anaplastic lymphoma kinase in the pathogenesis of cancer.
2008,
Pubmed
Choi,
EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors.
2010,
Pubmed
,
Echinobase
Cui,
NPM-ALK inhibits the p53 tumor suppressor pathway in an MDM2 and JNK-dependent manner.
2009,
Pubmed
Drexler,
Pathobiology of NPM-ALK and variant fusion genes in anaplastic large cell lymphoma and other lymphomas.
2000,
Pubmed
Elyakim,
hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy.
2010,
Pubmed
Gao,
MicroRNA-193a represses c-kit expression and functions as a methylation-silenced tumor suppressor in acute myeloid leukemia.
2011,
Pubmed
George,
Activating mutations in ALK provide a therapeutic target in neuroblastoma.
2008,
Pubmed
Gerber,
ALK inhibition for non-small cell lung cancer: from discovery to therapy in record time.
2010,
Pubmed
Guttilla,
Coordinate regulation of FOXO1 by miR-27a, miR-96, and miR-182 in breast cancer cells.
2009,
Pubmed
Janoueix-Lerosey,
Somatic and germline activating mutations of the ALK kinase receptor in neuroblastoma.
2008,
Pubmed
Katayama,
Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK.
2011,
Pubmed
,
Echinobase
Kelleher,
The emerging pathogenic and therapeutic importance of the anaplastic lymphoma kinase gene.
2010,
Pubmed
Kwak,
Anaplastic lymphoma kinase inhibition in non-small-cell lung cancer.
2010,
Pubmed
Marzec,
Oncogenic tyrosine kinase NPM/ALK induces activation of the MEK/ERK signaling pathway independently of c-Raf.
2007,
Pubmed
Mencía,
Mutations in the seed region of human miR-96 are responsible for nonsyndromic progressive hearing loss.
2009,
Pubmed
Morris,
ALK, the chromosome 2 gene locus altered by the t(2;5) in non-Hodgkin's lymphoma, encodes a novel neural receptor tyrosine kinase that is highly related to leukocyte tyrosine kinase (LTK).
1997,
Pubmed
Morris,
Fusion of a kinase gene, ALK, to a nucleolar protein gene, NPM, in non-Hodgkin's lymphoma.
1994,
Pubmed
Mossé,
Identification of ALK as a major familial neuroblastoma predisposition gene.
2008,
Pubmed
Pramanik,
Restitution of tumor suppressor microRNAs using a systemic nanovector inhibits pancreatic cancer growth in mice.
2011,
Pubmed
Qiu,
Autocrine release of interleukin-9 promotes Jak3-dependent survival of ALK+ anaplastic large-cell lymphoma cells.
2006,
Pubmed
Shi,
IGF-IR tyrosine kinase interacts with NPM-ALK oncogene to induce survival of T-cell ALK+ anaplastic large-cell lymphoma cells.
2009,
Pubmed
Soda,
Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer.
2007,
Pubmed
,
Echinobase
Staber,
The oncoprotein NPM-ALK of anaplastic large-cell lymphoma induces JUNB transcription via ERK1/2 and JunB translation via mTOR signaling.
2007,
Pubmed
Swarbrick,
miR-380-5p represses p53 to control cellular survival and is associated with poor outcome in MYCN-amplified neuroblastoma.
2010,
Pubmed
Wiggins,
Development of a lung cancer therapeutic based on the tumor suppressor microRNA-34.
2010,
Pubmed
Yu,
miRNA-96 suppresses KRAS and functions as a tumor suppressor gene in pancreatic cancer.
2010,
Pubmed
Zamo,
Anaplastic lymphoma kinase (ALK) activates Stat3 and protects hematopoietic cells from cell death.
2002,
Pubmed
