miR-363 acts as a tumor suppressor in osteosarcoma cells by inhibiting PDZD2

He,Fan; Fang,Long; Yin,Qingshui

doi:10.3892/or.2019.7078

miR-363 acts as a tumor suppressor in osteosarcoma cells by inhibiting PDZD2

Authors:
- Fan He
- Long Fang
- Qingshui Yin
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Affiliations: Department of Orthopedic, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Orthopedic, Shandong Academy of Medical Sciences, Shandong Cancer Hospital Affiliated to Shandong University, Jinan, Shandong 250117, P.R. China
Published online on: March 19, 2019 https://doi.org/10.3892/or.2019.7078
Pages: 2729-2738
Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

PDZ domain containing 2 (PDZD2) is a multi-PDZ domain protein that promotes the proliferation of insulinoma cells, and is upregulated during prostate tumorigenesis. However, the function of PDZD2 in other cancers, including osteosarcoma (OS), remains unclear. Dysregulation of microRNAs (miRNAs) contributes to tumor initiation, proliferation and metastasis, via the regulation of their target genes. The present study investigated the functions of miR-363 and PDZD2 in MG-63 OS cells. The results revealed that MG-63 cells contained low levels of miR-363, and that overexpression of miR-363 in MG-63 cells significantly inhibited the vitality, proliferation, and colony formation ability of the cells, but promoted their apoptosis and G1/S arrest by regulating proliferating cell nuclear antigen (PCNA) and caspase-3 expression. Additionally, miR-363 impaired the migration and invasion of MG-63 cells by regulating the epithelial-mesenchymal transition (EMT) phenotype. Notably, a bioinformatics analysis and luciferase reporter assay indicated that PDZD2 was a direct target of miR-363. miR-363 overexpression reduced PDZD2 protein levels and knockdown of PDZD2 suppressed the colony formation, migration and invasion of MG-63 cells, but promoted their apoptosis by regulating expression of PCNA, caspase-3, and the EMT phenotype. In vivo studies further confirmed that miR-363 functioned as tumor suppressor, by inhibiting tumor growth, promoting cell apoptosis, and reducing PDZD2 and PCNA levels and the prevalence of the EMT phenotype in tumor tissues. The present data demonstrated that downregulation of the tumor suppressor miR-363 may be involved in the development of osteosarcoma via regulation of PDZD2.

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