Background: The inhibitor of growth (ING) gene family of tumor suppressors is involved in multiple cellular functions such as cell cycle regulation, apoptosis, and chromatin remodeling. ING5 is a new member of the ING family whose function and regulation remain largely unknown.
Methods: Quantitative real-time PCR and western blot were used to examine the expression levels of ING5 in breast cancer tissues. The miRNAs that potentially targeted ING5 were determined by bioinformatics analysis and luciferase reporter assay. Cell viability assay, transwell invasion and apoptosis assay were used to characterize the changes induced by overexpressing or knocking down miR-24 or ING5. Hematoxylin and eosin (H&E) staining and immunohistochemical staining for ING5 and Ki-67 were used for xenograft assays in BALB/c nude mice.
Results: We showed that the ING5 protein rather than the mRNA, was significantly downregulated in breast cancer tissues. We also investigated the potential function of ING5 in breast tumorigenesis and found that ING5 suppressed the proliferation and invasion of breast cancer cells and promoted their apoptosis. Furthermore, we explored the molecular mechanisms accounting for the dysregulation of ING5 in breast cancer cells and identified an oncomiR, miR-24, as a direct upstream regulator of ING5. We revealed that miR-24 had the opposite effects to those of ING5 on breast cancer cells and could accelerate xenografted tumor growth in vivo.
Conclusion: Our findings uncover the tumor-suppressive role of ING5 and the regulatory pathway of ING5 in breast cancer and may provide insights into the molecular mechanisms of breast carcinogenesis.
Keywords: Apoptosis; Breast cancer; ING5; Invasion; Proliferation; miR-24; microRNA.