MicroRNA-373 Promotes Growth and Cellular Invasion in Osteosarcoma Cells by Activation of the PI3K/AKT-Rac1-JNK Pathway: The Potential Role in Spinal Osteosarcoma

• Published in: Oncology research Vol. 25; no. 6; pp. 989 - 999
• Main Authors: Liu, Yufeng, Cheng, Zhengliang, Pan, Feng, Yan, Weigang
• Format: Journal Article
• Language: English
• Published: Elmsford, NY Cognizant Communication Corporation 05.07.2017
• Subjects: Adolescent; Adult; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Cell Line, Tumor; Cell Movement - genetics; Female; Gene Expression Regulation, Neoplastic; Humans; Male; MAP Kinase Signaling System - genetics; Metastasis; Microrna-373 (mir-373); MicroRNAs - genetics; Osteosarcoma - genetics; Osteosarcoma - pathology; p53; Phosphatidylinositol 3-Kinases - metabolism; Pi3k/akt-Rac1-Jnk Pathway; Proto-Oncogene Proteins c-akt - metabolism; rac1 GTP-Binding Protein - genetics; rac1 GTP-Binding Protein - metabolism; Signal Transduction; Spinal Neoplasms - genetics; Spinal Neoplasms - pathology; Spinal Osteosarcoma (os); Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism
• DOI: 10.3727/096504016X14813867762123
• ISSN: 0965-0407; 1555-3906

Spinal osteosarcoma (OS) has been proven to be more difficult to treat owing to potently malignant metastasis. The present study aimed to explore the functional role of microRNA (miR)-373 in cell growth and invasion of OS cells, as well as its underlying mechanism. The expression of miR-373 was analyzed in spinal OS tissues and cell lines. MG-63 cells were transfected with the miR-373 mimic or inhibitor and/or treated with the phosphoinositide 3-kinase (PI3K) (LY294002) inhibitor or Ras-related C3 botulinum toxin substrate 1 (Rac) guanosine triphosphate (GTPase) (NSC23766) inhibitor, and then the impact of miR-373 aberrant expression on cell growth and invasion was measured, along with the impact of overexpressing miR-373 on the expression of p53 and PI3K/AKT pathway-related proteins. We found that miR-373 was specifically upregulated in spinal OS tissues (p < 0.01) and OS cell lines (p < 0.01 or p < 0.001). Moreover, miR-373 expression was significantly associated with TNM stage (p = 0.035) and tumor size (p = 0.002). Overexpression of miR-373 promoted MG-63 cell viability, migration, invasion, and colony formation (all p < 0.05), while silencing of miR-373 and LY294002 exerted the opposite effects. Additionally, miR-373 overexpression downregulated p53 as well as its downstream targeted genes and orderly activated the PI3K/AKT-Rac1-JNK signaling pathway. In conclusion, miR-373 promotes growth and cellular invasion in OS cells by activating the PI3K/AKT-Rac1-JNK pathway. Therefore, miR-373 might be a candidate for molecular targeted therapy of spinal OS.