Involvement of miR-769-5p/Retinoic Acid Receptor Responder 1 Axis in the Progression of Osteosarcoma: Characterization of Potential Therapeutic Targets

Introduction: This study aimed to detect the function of retinoic acid receptor responder 1 (RARRES1) and its regulator miR-769-5p in the growth and mobility of osteosarcoma cells.

Methods: The Gene Expression Omnibus database was applied to analyze RARRES1 and miR-769-5p expression, and the survival rate of osteosarcoma patients. The target association between miR-769-5p and RARRES1 was speculated by miRWalk, TargetScan, and miRanda Web sites, as well as affirmed by dual luciferase assay. RARRES1 expression was tested by quantitative real-time polymerase chain reaction and Western blot. The malignant properties of MG-63 and U2OS cells were assessed by a series of biological experiments.

Results: RARRES1 was lowly expressed in osteosarcoma patients, which resulted in unfavorable survival. Depletion of RARRES1 promoted the viability and mobility of osteosarcoma cells. Moreover, miR-769-5p was affirmed as an upstream regulator of RARRES1 and negatively regulated RARRES1 expression. miR-769-5p upregulation accelerated the viability and mobility of osteosarcoma cells, which can be blocked by RARRES1 overexpression. miR-769-5p inhibitor suppressed the effect of malignant viability and mobility of osteosarcoma cells, while this suppressive effect was abolished by depleting RARRES1.

Discussion/conclusion: miR-769-5p promoted cell viability, invasion, and migration by reducing RARRES1 expression in osteosarcoma cells, which might provide novel targets for the treatment of osteosarcoma.