Published in the "Proceedings of the Texas A&M Medical Student Grand Rounds" Journal

1. The role of selected microRNAs (miRNAs) in the negative regulation of pediatric
retinoblastoma progression
Ashtyn Zapletal
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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2016;5(4):260-264. doi:10.1097/apo.0000000000000219.
2. Plousiou M, Vannini I. Non-Coding RNAs in Retinoblastoma. Front Genet. 2019;10:1155. Published
2019 Nov 14. doi:10.3389/fgene.2019.01155
3. 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.
4. 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
5. 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
6. 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.
7. 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.