Downregulation of MST4 Underlies a Novel Inhibitory Role of MicroRNA Let-7a in the Progression of Retinoblastoma

Investigative Ophthalmology & Visual Science
Xinli ZhangHongxia Li

Abstract

Retinoblastoma (RB) is the most common intraocular malignancy in children. Deregulation of several microRNAs (miRNAs) has been identified in RB. However, the specific effect of let-7a on RB remains unclear. The present study aims to explore the effect of let-7a on malignant biological behaviors of RB cells and angiogenesis in RB. The expressions of let-7a and mammalian sterile-20 like kinase 4 (MST4) in RB were determined with the use of real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Next, in order to explore effects of let-7a and MST4 on RB cellular functions, RB cells were transfected with let-7a-mimic, let-7a inhibitor, si-MST4, or co-transfected with let-7a-mimic and oe-MST4 plasmids. Subsequently, the interaction among let-7a, MST4, and the MAPK signaling pathway was evaluated by RT-qPCR, dual-luciferase reporter gene assay, and Western blot analysis. Finally, the effects of let-7a and MST4 were further confirmed in vivo by injecting nude mice with RB cells stably expressing let-7a agomir or sh-MST4. Rb tissues and cells presented with downregulated Let-7a and upregulated MST4. Let-7a negatively targeted MST4 to block the activation of the MAPK signaling pathway. Upregulation of let-7...Continue Reading

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Datasets Mentioned

BETA
GSE5222

Methods Mentioned

BETA
PCR
electrophoresis
transfection
xenograft

Software Mentioned

SPSS
Image J
limma
Pro Plus
Image

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