MicroRNA-29c-3p inhibits osteosarcoma cell proliferation through targeting PIK3R3

H.-Z. Ma, J. Wang, J. Shi, W. Zhang, D.-S. Zhou

Department of Orthopedic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China. mahuanzhi2006@163.com

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• Oncology

OBJECTIVE: MicroRNAs (miRNAs) are endogenous, non-coding small RNAs involving in pathological regulation. Previous studies have shown that microRNA-29c-3p is a tumor-suppressor gene. However, the role of microRNA-29c-3p in osteosarcoma (OS) has not been reported. This study aims to investigate the potential influence of microRNA-29c-3p on the progression of OS.

PATIENTS AND METHODS: Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) was applied to examine microRNA-29c-3p levels in 40 matched pairs of OS tumor tissues and adjacent ones. The correlation between microRNA-29c-3p expression and clinical indicators in OS patient was analyzed. At the same time, qRT-PCR was used to detect microRNA-29c-3p level in OS cell lines. In addition, microRNA-29c-3p knockdown and the overexpression models were constructed in OS cell lines. The effects of microRNA-29c-3p on the biological functions of OS cells were analyzed via cell counting kit-8 (CCK-8) and transwell assays. Finally, the potential mechanism underlying microRNA-29c-3p in OS was explored by Western Blot and cell recovery experiment.

RESULTS: QRT-PCR results revealed that microRNA-29c-3p level in OS tumor tissues was conspicuously lower than that in adjacent tissues. Compared with OS patients with the high expression of microRNA-29c-3p, those with low expression of microRNA-29c-3p had a higher incidence of distant metastasis and worse overall survival. Cell proliferative capacity and invasiveness in OS were enhanced after knockdown of microRNA-29c-3p; while the opposite results were observed after the overexpression of microRNA-29c-3p. QRT-PCR results revealed that microRNA-29c-3p negatively regulated PIK3R3 expression in OS cells. Moreover, microRNA-29c-3p and PIK3R3 levels were confirmed to be negatively correlated in OS tissues. In addition, cell reverse experiment demonstrated that PIK3R3 was responsible for the malignant progression of OS regulated by microRNA-29c-3p.

CONCLUSIONS: MicroRNA-29c-3p expression was reduced in OS, and conspicuously associated with distant metastasis and poor prognosis. MicroRNA-29c-3p might inhibit the malignant progression of OS by modulating PIK3R3 expression.

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