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

Abstract

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 allocated 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.

Identification of key biomarkers and functional pathways in osteosarcomas with lung metastasis: Evidence from bioinformatics analysis

“…For example, miR-340-5p could negatively regulate Wnt/ β-catenin signaling pathway through targeting STAT3 gene, thereby inhibiting the development of osteosarcoma [65] . Meanwhile, overexpression of miR-340-5p could down-regulate the CTNNB1-mediated Notch signaling pathway, thereby suppressing osteosarcoma migration and invasion [66] . However, the regulatory relationships between miR-340-5p and these hub genes in patients with lung metastasis of osteosarcoma need to be con rmed by further studies.…”

miR-340: A multifunctional role in human malignant diseases

“…Furthermore, miR-340 was shown to be a potential therapeutic agent for GBM via its inhibitory effects on Bcl-w-induced platelet-derived growth factor-A (PDGF-A) and Sox2 activation 53 . A recent study revealed that miR-340 could suppress osteosarcoma (OS) cell proliferation by inactivating the Notch signaling pathway by down-regulating CTNNB1 54 . It has been reported that the overexpression of miR-340 inhibited human esophageal squamous cell carcinoma (ESCC) cell growth by modulating the expression of phosphoserine aminotransferase 1 ( PSAT1 ), and it may contribute to the progression of ESCC 55 .…”

Cell proliferation is induced in renal cell carcinoma through miR‑92a‑3p upregulation by targeting FBXW7

“…At present, miRNAs dysregulation is an area of great interest when investigating the molecular mechanisms of renal tumorigenesis (30). Numerous studies reported that miRNAs serve crucial roles in the regulation of various cellular processes, including cell cycle control, proliferation, migration and apoptosis (31,32). Furthermore, aberrant miRNA expression has been associated with a wide range of human diseases, including cancer (33)(34)(35).…”