HOXB5 Enhances Cellular Growth, Mobility, and Invasion in Retinoblastoma by Regulating the STAT3 Signaling Pathway

Abstract

Background: Retinoblastoma (RB) is a malignant tumor of the retina, and occurs usually in infants. However, the homeobox gene B5 (HOXB5)/signal transducer and activator of transcription 3 (STAT3) pathway is predominantly involved in many cancer types but has never been explored in RB. Therefore, we aimed to investigate the molecular mechanism underlying the HOXB5/STAT3 pathway in the progression of RB. Methods: The expression level of HOXB5, both at RNA and protein levels, within RB cells and tissues was assessed using various approaches, including immunocytochemistry, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), and western blot analysis. Furthermore, three types of transfected cell models were developed, including a group of cells with knocked-down or deleted HOXB5, another group with overexpressed HOXB5, and the third group with HOXB5 deleted+STAT3 overexpressed. Finally, the viability, metastasis, and apoptosis of RB cells were determined using Cell Counting Kit-8 (CCK-8) assay, Transwell analysis, and flow cytometry. Results: We observed an increase in the expression levels of HOXB5 and STAT3 in RB tissues and cells (p < 0.05). Furthermore, it was found that the overexpression of HOXB5 increased the viability (p < 0.01), migration (p < 0.05), and invasion capability (p < 0.05), and inhibited apoptosis in RB cells (p < 0.001). HOXB5 deletion reduced the viability and the number of migration and invasion of RB cells and increased the number of cell apoptosis (p < 0.001). Moreover, the silencing of HOXB5 decreased the expression level of STAT3 (p < 0.01), while the overexpression of STAT3 reversed the HOXB5 silence-induced RB cell inhibition effect (p < 0.001). Conclusions: These findings suggest that HOXB5 enhances the proliferation and metastasis of RB cells by regulating the STAT3 signaling pathway.