期刊
BIOLOGY OPEN
卷 2, 期 7, 页码 675-685出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.20134507
关键词
Frizzled 9; MDM2; Non-small cell lung cancer; p53; Wnt7a; hsa-miR29b
类别
资金
- U.S. Department of Veterans Affairs, NIH [R01CA138528-2522717, 5R21CA153268-02]
In non-small cell lung cancer cell lines, activation of beta-catenin independent signaling, via Wnt7a/Frizzled9 signaling, leads to reversal of cellular transformation, reduced anchorage-independent growth and induction of epithelial differentiation. miRNA expression profiling on a human lung adenocarcinoma cell line (A549) identified hsa-miR29b as an important downstream target of Wnt7a/Frizzled9 signaling. We show herein that hsa-miR29b expression is lost in non-small cell lung cancer (NSCLC) cell lines and stimulation of beta-catenin independent signaling, via Wnt7a expression, in NSCLC cell lines results in increased expression of hsa-miR29b. Surprisingly, we also identify specific regulation of hsa-miR29b by Wnt7a but not by Wnt3, a ligand for beta-catenin-dependent signaling. Interestingly, knockdown of hsa-miR29b was enough to abrogate the tumor suppressive effects of Wnt7a/Frizzled9 signaling in NSCLC cells, suggesting that hsa-miR29b is an important mediator of beta-catenin independent signaling. Finally, we show for the first time that hsa-miR29b plays an important role as a tumor suppressor in lung cancer by targeting murine double mutant 2 (MDM2), revealing novel nodes for Wnt7a/Frizzled9-mediated regulation of NSCLC cell proliferation. (C) 2013. Published by The Company of Biologists Ltd.
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