Journal
JOURNAL OF CELLULAR BIOCHEMISTRY
Volume 120, Issue 2, Pages 2657-2670Publisher
WILEY
DOI: 10.1002/jcb.27580
Keywords
apoptosis; invasion; microRNA-940 (miR-940); migration; osteosarcoma (OS); proliferation; secreted frizzled-related protein 1 (SFRP1); Wnt; -catenin signaling pathway
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Funding
- Jiangxi Youth Science Foundation [20161BAB215228]
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Osteosarcoma (OS) is the most common malignant tumor of bone with a high potential for metastasis. This study intends to explore whether microRNA-940 (miR-940) affects the development of OS cells and the underlying mechanism. OS and adjacent normal tissues were collected from OS patients; the OS cell line with the highest expression of miR-940 was selected, which was then subjected to transfection of miR-940 mimic, miR-940 inhibitor, siRNA-secreted frizzled-related protein 1 (SFRP1) or LiCl (agonists of Wnt/-catenin pathway) to identify regulation of miR-940 to OS cells through SFRP1. The targeting relationship between miR-940 and SFRP1 was verified using dual-luciferase reporter gene assay. Reverse-transcription quantitative polymerase chain reaction and Western blot assay were performed to determine miR-940, SFRP1, -catenin, and cyclinD1 and apoptosis-related genes Fas, Bax, and Bcl-2. MTT (3-(4, 5-dimethylthiazol-2-Yl)-2, 5-diphenyltetrazolium bromide) assay, scratch test, transwell assay, and flow cytometry were carried out to detect proliferation, migration, invasion, and apoptosis, respectively. Nude mice models were established to observe the tumor formation. Higher expression of miR-940, -catenin, and cyclinD1 and lower SFRP1 expression were identified in OS tissues. miR-940 targeted and negatively regulated SFRP1 expression. Furthermore, upregulated miR-940 expression activated the Wnt/-catenin signaling pathway in OS. With the treatment of miR-940 mimic, LiCL, or siRNA-SFRP1, OS cells showed promoted proliferation, migration, invasion, tumor formation, and impeded apoptosis (further reflected by elevated Bcl-2 expression and reduced Fas and Bax expression). The study demonstrates that miR-940 can promote the proliferation, migration, and invasion but suppress the apoptosis of human OS cells by downregulating SFRP1 through activating Wnt/-catenin signaling pathway.
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