hsa-miR29b, a critical downstream target of non-canonical Wnt signaling, plays an anti-proliferative role in non-small cell lung cancer cells via targeting MDM2 expression

作者：Avasarala Sreedevi; Van Scoyk Michelle; Wang Jianbin; Sechler Marybeth; Vandervest Katherine; Brzezinski Christine; Weekes Colin; Edwards Michael G; Arcaroli John; Davis Richard E; Bikkavilli Rama Kamesh; Winn Robert A^*

来源：Biology Open, 2013, 2(7): 675-685.

DOI：10.1242/bio.20134507

• Frizzled 9
• MDM2
• Non-small cell lung cancer
• p53
• Wnt7a
• hsa-miR29b

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.

• 出版日期2013-7-15