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LncRNA MBLN1-AS1 inhibits the progression of retinoblastoma through targeting miR-338-5p-Wnt/β-catenin signaling pathway

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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.

References

  1. Hao F, Mou Y, Zhang L, Wang S, Yang Y. LncRNA AFAP1-AS1 is a prognostic biomarker and serves as oncogenic role in retinoblastoma. Biosci Rep. 2018;38(3):BSR20180384.

    Article  CAS  Google Scholar 

  2. Fabian ID, Onadim Z, Karaa E, et al. The management of retinoblastoma. Oncogene. 2018;37(12):1551–60.

    Article  CAS  Google Scholar 

  3. Rao R, Honavar SG. Retinoblastoma. Indian J Pediatr. 2017;84(12):937–44.

    Article  Google Scholar 

  4. Wei X, Wang B, Wang Q, et al. MiR-362-5p, which is regulated by long non-coding RNA MBNL1-AS1, promotes the cell proliferation and tumor growth of bladder cancer by targeting QKI. Front Pharmacol. 2020;11:164.

    Article  CAS  Google Scholar 

  5. Fu XM, Guo W, Li N, et al. The expression and function of long noncoding RNA lncRNA-ATB in papillary thyroid cancer. Eur Rev Med Pharmacol Sci. 2017;21(14):3239–46.

    PubMed  Google Scholar 

  6. Yang G, Fu Y, Lu X, Wang M, Dong H, Li Q. LncRNA HOTAIR/miR-613/c-met axis modulated epithelial-mesenchymal transition of retinoblastoma cells. J Cell Mol Med. 2018;22(10):5083–96.

    Article  CAS  Google Scholar 

  7. Wei X, Yang X, Wang B, et al. LncRNA MBNL1-AS1 represses cell proliferation and enhances cell apoptosis via targeting miR-135a-5p/PHLPP2/FOXO1 axis in bladder cancer. Cancer Med. 2020;9(2):724–36.

    Article  CAS  Google Scholar 

  8. Zhu K, Wang Y, Liu L, Li S, Yu W. Long non-coding RNA MBNL1-AS1 regulates proliferation, migration, and invasion of cancer stem cells in colon cancer by interacting with MYL9 via sponging microRNA-412-3p. Clin Res Hepatol Gastroenterol. 2020;44(1):101–14.

    Article  CAS  Google Scholar 

  9. Wang JH, Zhang L, Huang ST, et al. Expression and prognostic significance of MYL9 in esophageal squamous cell carcinoma. PLoS ONE. 2017;12(4):e0175280.

    Article  Google Scholar 

  10. Li P, Xing W, Xu J, et al. microRNA-301b-3p downregulation underlies a novel inhibitory role of long non-coding RNA MBNL1-AS1 in non-small cell lung cancer. Stem Cell Res Ther. 2019;10(1):144.

    Article  Google Scholar 

  11. Zhou P, Li X. Serum miR-338-5p has potential for use as a tumor marker for retinoblastoma. Oncol Lett. 2019;18(1):307–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Gao Y, Lu X. Decreased expression of MEG3 contributes to retinoblastoma progression and affects retinoblastoma cell growth by regulating the activity of Wnt/beta-catenin pathway. Tumour Biol. 2016;37(2):1461–9.

    Article  CAS  Google Scholar 

  13. Wu T, Wang LN, Tang DR, Sun FY. SOST silencing promotes proliferation and invasion and reduces apoptosis of retinoblastoma cells by activating Wnt/beta-catenin signaling pathway. Gene Ther. 2017;24(7):399–407.

    Article  CAS  Google Scholar 

  14. Yang M, Li Y, Wei W. MicroRNA-188-5p promotes epithelial-mesenchymal transition by targeting ID4 through Wnt/betacatenin signaling in retinoblastoma. Onco Targets Ther. 2019;12:10251–62.

    Article  CAS  Google Scholar 

  15. Oshikawa M, Tsutsui C, Ikegami T, et al. Full-length transcriptome analysis of human retina-derived cell lines ARPE-19 and Y79 using the vector-capping method. Invest Ophthalmol Vis Sci. 2011;52(9):6662–70.

    Article  CAS  Google Scholar 

  16. Liu Y, Hu H, Liang M, et al. Regulated differentiation of WERI-Rb-1 cells into retinal neuron-like cells. Int J Mol Med. 2017;40(4):1172–84.

    Article  CAS  Google Scholar 

  17. Xu L, Li W, Shi Q, et al. MicroRNA936 inhibits the malignant phenotype of retinoblastoma by directly targeting HDAC9 and deactivating the PI3K/AKT pathway. Oncol Rep. 2020;43(2):635–45.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Ju C, Zhou R, Sun J, et al. LncRNA SNHG5 promotes the progression of osteosarcoma by sponging the miR-212-3p/SGK3 axis. Cancer Cell Int. 2018;18:141.

    Article  Google Scholar 

  19. Li J, Guo Y, Duan L, et al. AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling. Oncotarget. 2017;8(20):33694–703.

    Article  Google Scholar 

  20. Wu XZ, Cui HP, Lv HJ, Feng L. Knockdown of lncRNA PVT1 inhibits retinoblastoma progression by sponging miR-488–3p. Biomed Pharmacother. 2019;112:108627.

    Article  CAS  Google Scholar 

  21. Huo Y, Wang Q, Liu Y, et al. A temperature-sensitive phase-change hydrogel of topotecan achieves a long-term sustained antitumor effect on retinoblastoma cells. Onco Targets Ther. 2019;12:6069–82.

    Article  CAS  Google Scholar 

  22. Aldred SF, Collins P, Trinklein N. Identifying targets of human micrornas with the LightSwitch Luciferase Assay System using 3’UTR-reporter constructs and a microRNA mimic in adherent cells. J Vis Exp. 2011; (55).

  23. Song B, Lin HX, Dong LL, Ma JJ, Jiang ZG. MicroRNA-338 inhibits proliferation, migration, and invasion of gastric cancer cells by the Wnt/beta-catenin signaling pathway. Eur Rev Med Pharmacol Sci. 2018;22(5):1290–6.

    CAS  PubMed  Google Scholar 

  24. Zhang T, Liu W, Zeng XC, et al. Down-regulation of microRNA-338–3p promoted angiogenesis in hepatocellular carcinoma. Biomed Pharmacother. 2016;84:583–91.

    Article  CAS  Google Scholar 

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Authors and Affiliations

Authors

Contributions

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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Correspondence to Wanrong Liu.

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There are no conflict of interest in this investigation.

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Responsible Editor: John Di Battista.

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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

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