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Published on: July 30, 2020
Aurora Kinase B Expression, Its Regulation and Therapeutic Targeting in Human Retinoblastoma
Naheed Arfin Borah1,2, Swatishree Sradhanjali1,2, Manas Ranjan Barik1
1The Operation Eyesight Universal Institute for Eye Cancer, LV Prasad Eye Institute, Bhubaneswar, India.
Purpose:
Aurora kinase B (AURKB) plays a pivotal role in the regulation of mitosis and is gaining prominence as a therapeutic target in cancers; however, the role of AURKB in retinoblastoma (RB) has not been studied. The purpose of this study was to determine if AURKB plays a role in RB, how its expression is regulated, and whether it could be specifically targeted.
Methods:
The protein expression of AURKB was determined using immunohistochemistry in human RB patient specimens and immunoblotting in cell lines. Pharmacological inhibition and shRNA-mediated knockdown were used to understand the role of AURKB in cell viability, apoptosis, and cell cycle distribution. Cell viability in response to AURKB inhibition was also assessed in enucleated RB specimens. Immunoblotting was employed to determine the protein levels of phospho-histone H3, p53, p21, and MYCN. Chromatin immunoprecipitation-qPCR was performed to verify the binding of MYCN on the promoter region of AURKB.
Results:
The expression of AURKB was found to be markedly elevated in human RB tissues, and the overexpression significantly correlated with optic nerve and anterior chamber invasion. Targeting AURKB with small-molecule inhibitors and shRNAs resulted in reduced cell survival and increased apoptosis and cell cycle arrest at the G2/M phase. More importantly, primary RB specimens showed decreased cell viability in response to pharmacological AURKB inhibition. Additional studies have demonstrated that the MYCN oncogene regulates the expression of AURKB in RB.
Conclusions:
AURKB is overexpressed in RB, and targeting it could serve as a novel therapeutic strategy to restrict tumor cell growth.
Insights
Aurora kinase B (AURKB) is overexpressed in retinoblastoma (RB), a type of eye cancer. Targeting AURKB with inhibitors reduces tumor cell growth, offering a potential new therapy for RB patients.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Aurora kinase B (AURKB) is crucial for mitosis and a recognized cancer therapeutic target.
- The role of AURKB in retinoblastoma (RB), a pediatric eye cancer, remains uninvestigated.
Purpose of the Study:
- To investigate the role of AURKB in retinoblastoma.
- To determine the regulatory mechanisms of AURKB expression in RB.
- To evaluate AURKB as a potential therapeutic target for RB.
Main Methods:
- Immunohistochemistry and immunoblotting to assess AURKB protein expression in RB tissues and cell lines.
- Pharmacological inhibition and shRNA knockdown to analyze AURKB's impact on RB cell viability, apoptosis, and cell cycle.
- Chromatin immunoprecipitation-qPCR to confirm MYCN binding to the AURKB promoter.
Main Results:
- AURKB expression is significantly elevated in human RB tissues, correlating with tumor invasion.
- Inhibition of AURKB reduces RB cell survival, induces apoptosis, and causes G2/M cell cycle arrest.
- Primary RB specimens demonstrate reduced cell viability upon AURKB inhibition.
- The MYCN oncogene was identified as a regulator of AURKB expression in RB.
Conclusions:
- AURKB is overexpressed in retinoblastoma.
- Targeting AURKB presents a promising novel therapeutic strategy to inhibit retinoblastoma tumor growth.
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