Up-regulation of microRNA-340 promotes osteosarcoma cell apoptosis while suppressing proliferation, migration, and invasion by inactivating the CTNNB1-mediated Notch signaling pathway

Bao-Long Pan, Ling Wu, Li Pan, Yu-Xi Yang, Hu-Huan Li, Yan-Juan Dai, Zi-Qian He, Ling Tan, You-Guang Huang, Zong-Wu Tong, Jun-Long Liao
2018 Bioscience Reports  
Osteosarcoma (OS) is the most common histological form of primary bone cancer. It is most prevalent in teenagers and young adults. The present study aims at exploring the regulatory effect of microRNA-340 (miR-340) on OS cell proliferation, invasion, migration, and apoptosis via regulating the Notch signaling pathway by targeting β-catenin (cadherin-associated protein) 1 (CTNNB1). OS tissues belonging to 45 patients and normal femoral head tissues of 45 amputees were selected. Cells were
more » ... ed to different groups. In situ hybridization was performed to determine the positive rate of miR-340 expression while immunohistochemistry was used to determine that of CTNNB1 and B-cell lymphoma 2 (Bcl-2). We used a series of experiments to measure the expressions of related factors and assess rates of cell proliferation, migration, invasion, cycle, and apoptosis respectively. Our results show that miR-340 was expressed a higher level in normal tissue than OS tissue. Expression of Notch, CTNNB1, hairy and enhancer of split 1 (Hes1), Bcl-2, Runt-related transcription factor 2 (Runx2), and osteocalcin increased and that of miR-340, Bcl-2 interacting mediator of cell death (BIM), and Bcl-2 associated protein X (Bax) decreased in OS tissues. U-2OS cell line had the highest miR-340 expression. We also found that the up-regulation of miR-340 had increased expression of miR-340, BIM, and Bax but decreased expression of Notch, CTNNB1, Hes1, Bcl-2, Runx2, and osteocalcin. Up-regulation of miR-340p lead to increased cell apoptosis, suppressed cell proliferation, migration, and invasion. Our study demonstrates that overexpression of miR-340 could suppress OS cell proliferation, migration, and invasion as well as promoting OS cell apoptosis by inactivating the Notch signaling pathway via down-regulating CTNNB1. Functional miR-340 overexpression might be a future therapeutic strategy for OS.
doi:10.1042/bsr20171615 pmid:29769415 fatcat:n7dlnmwe2rdbfd7oorlxxjkv5e