ING5 suppresses breast cancer progression and is regulated by miR-24

Molecular Cancer

Research

Xin Liao¹  Xin Yin²  Hongwei Liang³  Yeting Hong³  Chao Ye³  Shufang Cui³  Xi Chen³  Minghui Liu³  Yanqing Liu³  Chen-Yu Zhang³  Mengchao Yu³ 

[1] Beihai Marine Station, Evo-devo Institute, School of Life Sciences, Nanjing University, 22 Hankou Road, 210093, Nanjing, Jiangsu, China;Department of Exercise and Heath, Nanjing Sport Institute, 8 Linggusi Road, 210014, Nanjing, Jiangsu, China;State Key Laboratory of Pharmaceutical Biotechnology, Collaborative Innovation Center of Chemistry for Life Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute for Life Sciences (NAILS), School of life sciences, Nanjing University, 210046, Nanjing, Jiangsu, China;

关键词: ING5;    microRNA;    miR-24;    Breast cancer;    Proliferation;    Invasion;    Apoptosis;   

DOI  :  10.1186/s12943-017-0658-z

 received in 2016-10-11, accepted in 2017-05-05,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsQuantitative 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.ResultsWe 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.ConclusionOur 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.

【 授权许可】

CC BY   
© The Author(s). 2017