Abstract
Retinoblastoma (RB) is the most common malignancy that occurs during childhood. Growing evidence supports a crucial role for microRNAs (miRNAs) in regulating the initiation and progression of RB. Aberrant expression of microRNA‑29a (miR‑29a) has been found in many types of cancers, but not including RB. Therefore, the aims of the present study were to evaluate the regulatory role and underlying mechanism of miR‑29a in human RB. In the present study, we found that miR‑29a expression was significantly downregulated in RB tissues and cell lines. Overexpression of miR‑29a in RB cells significantly inhibited cell proliferation, migration, and invasion and promoted cell apoptosis in vitro. Additionally, signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR‑29a in RB cells. miR‑29a overexpression in RB cells not only inhibited STAT3 expression but also altered expression of its downstream genes, including, Bcl2, cyclin D1 and matrix metalloproteinase 2 (MMP‑2). STAT3 mRNA expression was upregulated in RB tissues and negatively correlated with miR‑29a expression. Reintroduction of STAT3 without 3'‑untranslated region (3'UTR) reversed the inhibitory effects of miR‑29a on cell proliferation, migration and invasion. In vivo study confirmed that overexpression of miR‑29a also inhibited tumor formation of RB in a nude mouse model by repressing STAT3. Collectively, these data suggest that miR‑29a exerts a tumor suppressor effect on RB by repressing STAT3, supporting the targeting of miR‑29a as a potentially effective therapeutic method for RB.