title: 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.
abstract: 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.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Liu
authors.forename: Zhengliang
authors.initials: Z
authors.lastname: Cheng
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Weigang
authors.initials: W
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D001859:Bone Neoplasms / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D012516:Osteosarcoma / Q000235:genetics* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D013125:Spinal Neoplasms / Q000235:genetics* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism
chemical_list: C527114:MIRN373 microRNA, human; D035683:MicroRNAs; C107953:RAC1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D020830:rac1 GTP-Binding Protein