Long noncoding RNA SNHG14 promotes the aggressiveness of retinoblastoma by sponging microRNA-124 and thereby upregulating STAT3

摘要

A long noncoding RNA called small nucleolar RNA host gene 14 ( ) has been validated as a key regulator of cellular processes in multiple types of human cancer. However, to the best of our knowledge, the expression status and specific roles of in retinoblastoma (RB) have not been studied. The aims of the present study were to determine the expression status of in RB, assess the effects of on malignant characteristics of RB cells and investigate the mechanisms of action of in RB. expression levels in RB tissue samples and cell lines were measured by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Cell proliferation, apoptosis, migration and invasion , and tumor growth were quantitated by the Cell Counting Kit-8 assay, flow cytometry, migration and invasion assays, and mouse tumor xenograft experiments, respectively. The target microRNA (miRNA) of was predicted by bioinformatics analysis and was subsequently validated by a luciferase reporter assay, RNA immunoprecipitation (RIP) assay, RT-qPCR, and western blot analysis. was identified to be significantly overexpressed in RB tissues and cell lines. overexpression was markedly associated with the intraocular international retinoblastoma classification stage, optic nerve invasion, and differentiation grade among patients with RB. The patients in the high-expression group exhibited shorter overall survival compared with the low-expression group. Functional analysis revealed that silencing inhibited cell proliferation, migration and invasion, and increased apoptosis , and decreased tumor growth . directly interacted with, and functioned as a competing endogenous RNA (ceRNA) of, miR-124, consequently upregulating signal transducer and activator of transcription 3 (STAT3). miR-124 inhibition and STAT3 expression recovery attenuated the effects of the silencing on RB cells. In conclusion, served as a ceRNA to upregulate STAT3 by sponging miR-124. Therefore, targeting the /miR-124/STAT3 pathway may be an effective therapeutic strategy against RB.