miR-135b Stimulates Osteosarcoma Recurrence and Lung Metastasis via Notch and Wnt/β-Catenin Signaling

• Main Authors: Hua Jin (Author), Song Luo (Author), Yun Wang (Author), Chang Liu (Author), Zhenghao Piao (Author), Meng Xu (Author), Wei Guan (Author), Qing Li (Author), Hua Zou (Author), Qun-You Tan (Author), Zhen-Zhou Yang (Author), Yan Wang (Author), Dong Wang (Author), Cheng-Xiong Xu (Author)
• Format: Book
• Published: Elsevier, 2017-09-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Cancer stem cells (CSCs) play an important role in osteosarcoma (OS) metastasis and recurrence, and both Wnt/β-catenin and Notch signaling are essential for the development of the biological traits of CSCs. However, the mechanism that underlies the simultaneous hyperactivation of both Wnt/β-catenin and Notch signaling in OS remains unclear. Here, we report that expression of miR-135b correlates with the overall and recurrence-free survival of OS patients, and that miR-135b has an activating effect on both Wnt/β-catenin and Notch signaling. The overexpression of miR-135b simultaneously targets multiple negative regulators of the Wnt/β-catenin and Notch signaling pathways, including glycogen synthase kinase-3 beta (GSK3β), casein kinase 1a (CK1α), and ten-eleven translocation 3 (TET3). Therefore, upregulated miR-135b promotes CSC traits, lung metastasis, and tumor recurrence in OS. Notably, antagonizing miR-135b potently inhibits OS lung metastasis, cancer cell stemness, CSC-induced tumor formation, and recurrence in xenograft animal models. These findings suggest that miR-135b mediates the constitutive activation of Wnt/β-catenin and Notch signaling, and that the inhibition of miR-135b is a novel strategy to inhibit tumor metastasis and prevent CSC-induced recurrence in OS. Keywords: osteosarcoma, miR-135b, metastasis, recurrence, Wnt/β-catenin

Item Description

2162-2531
10.1016/j.omtn.2017.06.008