Decreased expression of miR-195 mediated by hypermethylation promotes osteosarcoma

Author:

Sun Tianhao12,Liu Dongning3,Wu Jun4,Lu William W.42,Zhao Xiaoli2,Wong Tak Man4,Liu Zhi-Li5

Affiliation:

1. Shenzhen Key Laboratory for Innovative Technology in Ortho-paedic Trauma, Guangdong Engineering Technology Research Center for Orthopaedic Trauma Repair, Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital , Shenzhen 518053 , China

2. Research Center for Human Tissue and Organs Degeneration, Institute Biomedicine and Biotechnology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences , Shenzhen 518055 , China

3. Department of Spinal Surgery, Shenzhen Sixth People’s Hospital(Nanshan Hospital), Huazhong University of Science and Technology Union Shenzhen Hospital , Shenzhen , China

4. Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, Guangdong Engineering Technology Research Center for Orthopaedic Trauma Repair, Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital , Shenzhen 518053 , China

5. Institute of Spine and Spinal Cord, Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University , Nanchang 330006 , China

Abstract

Abstract Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The early lung metastasis of osteosarcoma is one of the main factors of poor prognosis. Therefore, searching for new targets and new mechanisms of osteosarcoma metastasis is essential for the prevention and treatment of osteosarcoma. Our previous studies suggested that fatty acid synthase (FASN) was an oncogene and promoted osteosarcoma. In addition, it is reported that the expression of miR-195 was negatively correlated with osteosarcoma. Aberrant DNA methylation can reversely regulate the expression of miRNAs. However, whether miR-195 could target FASN in osteosarcoma and whether ectopic DNA methylation is the upstream regulatory mechanism of miR-195 in metastasis of osteosarcoma are not fully studied. The expressions were detected by qPCR and western blot, and methylation level was determined by methylation-specific PCR. Luciferase reporter assay, MTT, wound healing, and Transwell assay were used. We found that the expression of miR-195 was low in osteosarcoma. The methylation of miR-195 was high. miR-195 targeted and decreased the expression of FASN. In osteosarcoma, miR-195 inhibited cell proliferation, cell migration, and invasion. The methylation of miR-195 was related to decreased miR-195, it might promote osteosarcoma.

Publisher

Walter de Gruyter GmbH

Subject

General Medicine

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