Downregulation of microRNA‑198 suppresses cell proliferation and invasion in retinoblastoma by directly targeting PTEN.

Abstract

A number of studies have highlighted that aberrantly expressed microRNAs (miRNAs/miRs) serve crucial roles in the tumorigenesis and tumor development of retinoblastoma (RB). Hence, a full investigation of the biological roles and regulatory mechanisms of miRNAs in RB may provide novel therapeutic targets for patients with this malignancy. miR‑198 is frequently abnormally expressed in various types of human cancers. However, the expression level, biological roles and underlying mechanisms of miR‑198 in RB remain to be elucidated. In the present study, miR‑198 expression was upregulated in RB tissues and cell lines. Silencing of miR‑198 attenuated cell proliferation and invasion in RB. In addition, phosphatase and tensin homolog deleted on chromosome ten (PTEN) was predicted as a potential target of miR‑198 using bioinformatics analysis. Subsequent luciferase reporter assay indicated that the 3'‑untranslated region of PTEN can be directly targeted by miR‑198. Furthermore, miR‑198 inhibition increased the PTEN expression at the mRNA and protein levels in RB cells. In addition, PTEN mRNA expression was downregulated in RB tissues, and this downregulation was inversely associated with the expression level of miR‑198. PTEN knockdown rescued the inhibitory effects of miR‑198 underexpression on cell proliferation and invasion in RB. Notably, the downregulation of miR‑198 inactivated the phosphoinositide 3‑kinase (PI3K)/protein kinase B (AKT) signaling pathway in RB. These results demonstrated that miR‑198 may serve oncogenic roles in RB by directly targeting PTEN and regulating the PI3K/AKT signaling pathway. Hence, miR‑198 may be a promising therapeutic target for patients with RB.