AURKB overexpression

The rescue experiment presented that high expression of microRNA-486-5p could weaken the impact of AURKB overexpression on LUAD cell behavior and DDP resistance. microRNA-486-5p regulated DNA damage to inhibit DDP resistance in LUAD by targeting AURKB, implying that microRNA-486-5p/AURKB axis may be a possible therapeutic target for DDP resistance in LUAD patients.

Kaplan-Meier survival analysis, Cox regression analysis, and Receiver Operating Characteristic (ROC) curve analysis suggested that AURKB overexpression has good diagnostic and prognostic potential in HCC. Therefore, AURKB may be used as a potential target for the diagnosis and cure of HCC.

AURKB mRNA and protein expression levels were also significantly upregulated in MCF-7 cells, whereas its overexpression significantly reversed the effects of NCAPH knockdown on breast cancer cells and the Akt/mTOR signaling pathway. Overall, NCAPH knockdown significantly downregulated AURKB mRNA and protein expression levels to block the Akt/mTOR signaling pathway and inhibited breast cancer cell proliferation, migration, invasion, and aggravate DDP-resistant breast cancer cell apoptosis, indicating that NCAPH may serve as a promising therapeutic target for breast cancer.

To use a pharmacologic approach, we combined the pan-Aurora kinase inhibitor danusertib (0-2µM) with PI3K/mTOR inhibitor omipalisib (0-200nM) in 56 HNSCC cell lines for 72h and observed a substantial decrease in cell viability in >80% of NOTCH1WT and >90% of NOTCH1MUT HNSCC lines...Mice bearing NOTCH1MUT xenografts showed complete tumor regression when treated with a combination of pan-PI3K inhibitor Copanlisib and Aurora inhibitor Alisertib as compared to control groups...We identified AURKB as a central player governing the sensitivity to PI3K inhibitor-induced apoptosis in the context of NOTCH1 mutation status in HNSCC through its effects on AKT and PDK1. These novel findings may lead to the development of more robust therapeutic approach for NOTCH1 mutant squamous carcinoma as well as patients who develop acquired resistance to targeted therapies.

Using inhibitors of STAT3/5 and FAK, we reverted the invasive phenotype in both BRAF and NRAS mutated cells. Our findings confirm an increased invasive phenotype upon STK11-inactivation in BRAF and NRAS-mutant cutaneous melanoma that can be targeted by STAT3/5 and FAK-inhibition.

Additionally, AURKB overexpression could potentiate the invasion and the expression of MRP1 and Ki67, while suppresses apoptosis in SK-N-AS-R and IMR-32-R, whereas ERK inhibitor U0126 could reverse the phenomenon caused by AURKB overexpression. AURKB overexpression was strongly associated with poor prognosis and carboplatin resistant acquisition. Additionally, suppression of AURKB-ERK axis might be a potential therapy for carboplatin resistance in NB patients.