MicroRNA-1269a promotes the occurrence and progression of osteosarcoma by inhibit-ing TGF-β1 expression

OBJECTIVE: MicroRNAs are endogenous, non-coding small RNAs that are capable of regulating biological and pathological processes. Previous studies have shown that microRNA-1269a serves as an oncogene. However, the role of microRNA-1269a in the pathogenesis of osteosarcoma (OS) has not been reported. The aim of this work was to investigate the expression characteristics of microRNA-1269a in OS and to further study its regulatory effects on the malignant progression of OS.

PATIENTS AND METHODS: The expression of microRNA-1269a in 61 pairs of OS tissues and para-cancerous tissues was detected by quantitative Real Time-polymerase Chain Reaction (qRT-PCR). Chi-square test was used to analyze the relationship between microRNA-1269a expression and the characteristics of OS patients, including age, sex, clinical stage and distant metastasis. Subsequently, microRNA-1269a expression in OS cell lines was detected as well. After knockdown of microRNA-1269a by constructing relevant small interference RNA, biological performances of MG63 and U2OS cells were accessed by cell counting kit-8 (CCK-8), colony formation and transwell assay. Meanwhile, the protein expressions of key genes in the EMT/Smad pathway were detected by Western blot. Finally, si-TGF-β1 (transforming growth factor-β1) was transfected into OS cells, and cell migration and invasion were detected by transwell assay.

RESULTS: MicroRNA-1269a was highly expressed in OS tissues compared with para-cancerous tissues. High expression of microRNA-1269a was positively correlated with young OS patients and high rate of distant metastasis, whereas was not correlated with age, sex and Enneking stage. Kaplan-Meier survival curves showed that high expression of microRNA-1269a was significantly associated with poor prognosis of OS. The knockdown of microRNA-1269a in MG63 and U2OS cells significantly inhibited cell proliferation, migration and invasion. Meanwhile, microRNA-1269a knockdown in OS cells markedly downregulated the expressions of TGF-β1, p-Smad2, p-Smad3, N-cad, Vimentin and MMP9. Furthermore, TGF-β1 knockdown remarkably decreased migratory and invasive abilities of OS cells.

CONCLUSIONS: MicroRNA-1269a is highly expressed in OS, which is remarkably correlated with tumor stage, distant metastasis and poor prognosis of OS. In addition, microRNA-1269a promotes the malignant progression of OS by regulating TGF-β1 expression.

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