Downregulation of long non-coding RNA DBH-AS1 inhibits osteosarcoma progression by PI3K-AKT signaling pathways and indicates good prognosis

OBJECTIVE: Long non-coding RNA DBH-AS1 (DBH-AS1) has emerged as a novel regulator in cancer initiation and progression of several tumors. However, the expression of DBH-AS1 in osteosarcoma and its effect on the tumorigenesis of osteosarcoma are unclear. The purpose of this study was to determine the role of DBH-AS1 in osteosarcoma progression.

PATIENTS AND METHODS: The expression level of DBH-AS1 in 119 pairs of osteosarcoma tissues and five cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The association of DBH-AS1 expression with clinicopathological factors and prognosis was also analyzed. Cell proliferation was measured by Cell Counting Kit-8 (CCK-8), EdU and cell colony formation assays and apoptosis in MG63 and U2OS cells was examined by flow cytometry. Following that, transwell invasion and wound-healing assays were used to explore cell migration and invasion, respectively. The expression of the PI3K/Akt pathway-related proteins was examined by Western blot analysis.

RESULTS: We observed that DBH-AS1 was distinctly overexpressed in osteosarcoma tissue and cells, and associated with lymph node status and metastasis status. Osteosarcoma patients with a higher DBH-AS1 expression showed significantly poorer overall survival than those with lower DBH-AS1 expression. Multivariate analysis demonstrated that high DBH-AS1 expression was an independent poor prognostic factor for osteosarcoma patients. Functional assays revealed that knockdown of DBH-AS1 inhibited cell proliferation, migration and invasion, while promoted apoptosis in osteosarcoma. Moreover, suppression of DBH-AS1 could inhibit the activation of the PI3K/Akt pathway, which was demonstrated by examining the expression levels of p-PI3K and p-Akt.

CONCLUSIONS: Our data first reported that DBH-AS1 may act as an oncogenic lncRNA by modulating the PI3K/Akt pathway in osteosarcoma, which may serve as a candidate prognostic biomarker and target for new therapies in osteosarcoma.

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