|Title:||MicroRNA-135b promotes lung cancer metastasis by regulating multiple targets in the Hippo pathway and LZTS1||Authors:||Lin, C.-W.
|Issue Date:||2013||Publisher:||NATURE PUBLISHING GROUP||Journal Volume:||4||Journal Issue:||1||Source:||Nature Communications||Abstract:||
Dysregulation of microRNAs has a critical role in cancer progression. Here we identify an intronic microRNA, miR-135b that is upregulated in highly invasive non-small-cell lung cancer cells. Expression of miR-135b enhances cancer cell invasive and migratory abilities in vitro and promotes cancer metastasis in vivo, while specific inhibition of miR-135b by a miR-135b-specific molecular sponge and antagomirs suppresses cancer cell invasion, orthotopic lung tumour growth and metastasis in a mouse model. miR-135b targets multiple key components in the Hippo pathway, including LATS2, β-TrCP and NDR2, as well as LZTS1. Expression of miR-135b, LZTS1, LATS2 and nuclear TAZ predicts poor outcomes of non-small-cell lung cancer. We find that miR-135b is dually regulated by DNA demethylation and nuclear factor-kappaB signalling, implying that abnormal expression of miR-135b in cancer may result from inflammatory and epigenetic modulations. We conclude that miR-135b is an oncogenic microRNA and a potential therapeutic target for non-small-cell lung cancer. © 2013 Macmillan Publishers Limited. All rights reserved.
|Appears in Collections:||基因體暨蛋白體醫學研究所|
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