miR-577 inhibits glioblastoma tumor growth via the Wnt signaling pathway.

Abstract

microRNAs (miRNAs) are commonly altered in glioblastoma. Publicly available algorithms suggest the Wnt pathway is a potential target of miR-577 and the Wnt pathway is commonly altered in glioblastoma. Glioblastoma has not been previously evaluated for miR-577 expression. Glioblastoma tumors and cell lines were evaluated for their expression of miR-577. Cell lines were transfected with miR-577, miR-577-mutant, or control mimics to evaluate the effect of miR-577 expression on cell proliferation in vitro and in an animal model. Wnt pathway markers were also evaluated for their association with miR-577 expression. miR-577 expression was decreased in 33 of 40 (82.5%) glioblastoma tumors and 5 of 6 glioblastoma cell lines. miR-577 expression correlated negatively with cell growth and cell viability. miR-577 down-regulation was associated with increased expression of the Wnt signaling pathway genes lipoprotein receptor-related protein (LRP) 6 (LRP6) and β-catenin. Western blot analysis confirmed decreased expression of the Wnt signaling pathway genes Axin2, c-myc, and cyclin D1 in miR-577 transfected cells. miR-577 expression is down-regulated in glioblastoma. miR-577 directly targets Wnt signaling pathway components LRP6 and β-catenin. miR-577 suppresses glioblastoma multiforme (GBM) growth by regulating the Wnt signaling pathway.

• Authors: Weiguang Zhang, Chen Shen, Chenguang Li, Guang Yang, Huailei Liu, Xin Chen, Dan Zhu, Huichao Zou, Yunbo Zhen, Daming Zhang, Shiguang Zhao
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 55 Issue 5 Pg. 575-85 (May 2016) ISSN: 1098-2744 [Electronic] United States
• PMID: 25764520 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• LRP6 protein, human
• Low Density Lipoprotein Receptor-Related Protein-6
• MIRN577 microRNA, human
• MicroRNAs
• beta Catenin

Topics

• Animals
• Brain Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation
• Cell Survival
• Down-Regulation
• Gene Expression Regulation, Neoplastic
• Glioblastoma (genetics, metabolism, pathology)
• Humans
• Low Density Lipoprotein Receptor-Related Protein-6 (genetics)
• Male
• Mice
• MicroRNAs (genetics, metabolism)
• Neoplasm Transplantation
• Wnt Signaling Pathway
• beta Catenin (genetics)