期刊
INFLAMMATION RESEARCH
卷 70, 期 2, 页码 217-227出版社
SPRINGER BASEL AG
DOI: 10.1007/s00011-020-01432-z
关键词
MBNL1-AS1; miR-338-5p; Retinoblastoma; Proliferation; Migration
The study demonstrates that MBNL1-AS1 exerts its anti-tumor effect in retinoblastoma by targeting miR-338-5p, inhibiting cell proliferation and migration, and inactivating the Wnt/beta-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/beta-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/beta-catenin signaling pathway in retinoblastoma.
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