The Role of Selected MicroRNAs (miRNAs) in the Negative Regulation of Pediatric Retinoblastoma Progression
Introduction. Retinoblastoma (Rb) is an autosomal dominant retinal cancer usually affecting children ages 15 months – 24 months, counting for roughly 9,000 new cases each year.1,2 Common treatments for Rb include intra-ophthalmic and intra-vitreal chemotherapy, as well as enucleation3. To mitigate the harsh side effects of these current treatments, new therapeutics are of potential interest.3,4 MicroRNAs (miRNAs) have been shown to play a role in both protection from and development of carcinogenesis through the interplay of common biochemical pathways.2,4 A miRNome landscape analysis revealed a core of 30 miRNAs implicated in retinoblastoma.4 These findings suggest a prospective new treatment for Rb in the form of miRNA therapy. Methods. Levels of selected miRNAs from the core were compared between retinoblastoma and standard samples. qRT-PCR and luciferase reporter assays were used to quantify levels of miRNA-188-5p, miRNA-21, and miRNA-24.5-7 Tissues were analyzed for upregulation or downregulation of the miRNAs and statistical significance was calculated using one-way analysis of variance (ANOVA). Results. Results yielded differences among retinoblastoma and normal tissues. First, miRNA-188-5p was upregulated in WERI-Rb-1 and Y79 Rb tissues as compared to ARPE-19 control lines, promoting cell motility via the Wnt/β‑catenin signaling pathway.5 Second, levels of miRNA-21 were increased in WERI-Rb-1 cells, with an inhibitor lowering miRNA-21 concentrations and decreasing cell migration and invasion through the actions of PTEN on the PI3K/AKT pathway.6 Third, in Y79 cells, miRNA-24 was downregulated compared to ARPE-19 cells.7 MYC, a proto-oncogene that is a common denominator of both Wnt/β‑catenin and PI3K/AKT pathways, was shown to be inversely correlated to miRNA-24 levels.7 In summation, upregulated miRNA-188-5p and miRNA-21, along with downregulated miRNA-24, were associated with retinoblastoma progression.5-7 Conclusions. These results suggest that, because of the strong correlation between miRNAs and carcinogenesis, upregulation and downregulation of miRNAs have the potential to play a large regulatory role in retinoblastoma. Molecules such as miRNA-188-5p, miRNA-21, and miRNA-24 have been shown to be possible therapeutic avenues through their interactions amongst various biochemical pathways implicated in Rb. As the need for more efficacious treatments arise, further research must be done to pinpoint additional miRNAs with the potential to impede retinoblastoma advancement.
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- Fabian ID, Onadim Z, Karaa E, et al. The management of retinoblastoma. Oncogene. 2018;37(12):1551-1560. doi:10.1038/s41388-017-0050-x.
- Castro-Magdonel BE, Orjuela M, Camacho J, et al. miRNome landscape analysis reveals a 30 miRNA core in retinoblastoma. BMC Cancer. 2017;17(1):458. Published 2017 Jul 1. doi:10.1186/s12885-017-3421-3
- Yang M, Li Y, Wei W. MicroRNA-188-5p Promotes Epithelial-Mesenchymal Transition by Targeting ID4 Through Wnt/β‑catenin Signaling in Retinoblastoma. Onco Targets Ther. 2019;12:10251–10262. Published 2019 Nov 27. doi:10.2147/OTT.S229739
- Gui F, Hong Z, You Z, Wu H, Zhang Y. MiR-21 inhibitor suppressed the progression of retinoblastoma via the modulation of PTEN/PI3K/AKT pathway. Cell Biology International. 2016;40(12):1294-1302. doi:10.1002/cbin.10678.
- Yu F, Pang G, Zhao G. ANRIL acts as onco-lncRNA by regulation of microRNA-24/c-Myc, MEK/ERK and Wnt/β-catenin pathway in retinoblastoma.International Journal of Biological Macromolecules. 2019;128:583-592. doi:10.1016/j.ijbiomac.2019.01.157.