Abstract
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.
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Availability of data and materials
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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LX and WRL contributed to the conception and design of the study; LX, SYZ and ADT performed the experiments and collected the data; SYZ and ADT performed the statistical analysis; LX and SYZ completed data interpretation; LX and WRL wrote the manuscript and revised manuscript; All authors contributed to reading and revising the manuscript and approved the submitted version.
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Xu, L., Zhu, S., Tang, A. et al. LncRNA MBLN1-AS1 inhibits the progression of retinoblastoma through targeting miR-338-5p-Wnt/β-catenin signaling pathway. Inflamm. Res. 70, 217–227 (2021). https://doi.org/10.1007/s00011-020-01432-z
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DOI: https://doi.org/10.1007/s00011-020-01432-z