LncRNA MBLN1-AS1 Inhibits the Progression of Retinoblastoma Through Targeting MiR-338-5p-Wnt/β-catenin Signaling Pathway

Objective And Design: Retinoblastoma is the most common primary intraocular malignancy of childhood, which brings a heavy burden to the countries across the world, especially the developing countries. It has been shown that lncRNA muscleblind-like 1 antisense RNA 1 (MBNL1-AS1) exerts anti-tumor effects in various cancers, including bladder cancer, papillary thyroid cancer, and retinoblastoma. In the present study, we hypothesized that MBNL1-AS1 might play a protective role against retinoblastoma.

Methods: The expression of MBNL1-AS1 and its potential target miR-338-5p were evaluated in retinoblastoma cell line by real-time quantitative PCR and western blot. The involvement of MBNL1-AS1-miR-338-5p in the cell proliferation was evaluated by cell counting kit-8 (CCK8), and colony formation assay. The cell migration was evaluated by Transwell assay in Y79 cells, a retinoblastoma cell line. The involvement of MBNL1-AS1-miR-338-5p in tumor formation was also evaluated in mice.

Results: It was found that MBNL1-AS1 overexpression inhibited proliferation and migration in Y79 cells. In addition, the inhibitory effects of MBNL1-AS1 on Y79 cells were significantly reversed in the presence of miR-338-5p mimics, and MBNL1-AS1 overexpression significantly decreased miR-338-5p level in Y79 cells. Furthermore, MBNL1-AS1 overexpression significantly inhibited Wnt/β-catenin signaling pathway, and this inhibitory effect was almost lost in the presence of miR-338-5p mimics. Finally, our in vivo study showed that MBNL1-AS1 overexpression significantly inhibited Y79-induced retinoblastoma in mice, and this inhibitory effect was lost in the presence of miR-338-5p mimics.

Conclusion: Our study shows that MBNL1-AS1 exerts its anti-tumor effect by targeting miR-338-5p, thereby inactivating wnt/β-catenin signaling pathway in retinoblastoma.