circSLC39A8 by sponging hsa-miR-11181-5p and direct binding to PIK3CA mRNA promotes retinoblastoma proliferation.

Background: Retinoblastoma (RB) is a prevalent intraocular malignant tumor, posing a significant threat to human life and health. Although the involvement of circRNAs in various malignancies has been reported, their precise role in RB remains incompletely understood. Methods: High-throughput sequencing was utilized to construct differential expression profiles of circRNAs, followed by candidate gene screening using RT-qPCR. The circular structure of circSLC39A8 was confirmed through stability assays with RNase R and Act D. A research system for transiently silencing and overexpressing circSLC39A8 was established, with flow cytometry employed to assess cell cycle and apoptosis levels. Bioinformatics analyses, RT-qPCR, and western blot experiments were conducted to evaluate the expression of circSLC39A8, hsa-miR-11181-5p, and PIK3CA. RNA antisense purification experiments were performed to elucidate interactions among circSLC39A8, hsa-miR-11181-5p, and PIK3CA. Results: Our findings revealed a significant upregulation of circSLC39A8 in RB. Functionally, circSLC39A8 was identified as promoting cellular proliferation and suppressing apoptosis in vitro, thereby facilitating RB progression. Mechanistically, circSLC39A8 indirectly augmented the expression levels of PIK3CA mRNA by acting as a competitive endogenous RNA for hsa-miR-11181-5p, consequently enhancing the stability of PIK3CA mRNA and ultimately fostering RB cell proliferation while inhibiting apoptosis.