Abstract
Retinoblastoma (RB) is the most common type of intraocular malignancy in children. During RB oncogenesis, sonic hedgehog (SHH) is commonly differentially expressed. Additionally, microRNAs (miRs) are known to serve crucial roles as oncogenes or tumor suppressors. Specifically, miR-361-3p has been revealed to serve a vital role in cutaneous squamous cell carcinoma, cervical cancer, prostate cancer, colorectal cancer, gastric cancer, hepatocellular carcinoma, breast cancer and lung cancer. However, the role of miR-361-3p in RB and the potential molecular mechanisms involved remain unknown. Therefore, the current study aimed to determine the involvement of miR-361-3p in the development of RB by targeting SHH signaling. In the present study, miR-361-3p expression levels in RB tissue and serum samples obtained from 10 patients with RB, normal retinal tissue and serum samples obtained from 10 healthy controls, and two human RB cell lines (Y79 and Weri-Rb-1) were determined using reverse transcription-quantitative polymerase chain reaction. In addition, a cell counting kit-8 assay, a cell transfection assay, a MTT assay, western blotting, a tumor sphere formation assay and a luciferase assay were used to assess the expression, function and molecular mechanism of miR-361-3p in human RB. It was demonstrated that miR-361-3p was significantly downregulated in RB tissues, RB serum and RB cell lines compared with normal retinal tissues and normal serum. The ectopic expression of miR-361-3p decreased RB cell proliferation and stemness. Furthermore, GLI1 and GLI3 were verified as potential direct targets of miR-361-3p. miR-361-3p was also revealed to exhibit a negative correlation with GLI1/3 expression in RB samples. Taken together, the results indicate that miR-361-3p functions as a tumor suppressor in the carcinogenesis and progression of RB by targeting SHH signaling. Thus, miR-361-3p should be further assessed as a potential therapeutic target for RB treatment.