Functions And Molecular Mechanisms Of CircRNA,circFOXK2,in Breast Cancer

Breast cancer is one of the major cancers threatening women’s health worldwide,which not only causes economic burden to patients,but also increases their physical and mental pain.In China,breast cancer has the highest incidence and the fifth mortality rate in women.Although surgery,radiotherapy,chemotherapy and other treatments can largely control the development of breast cancer,the side effects caused by these treatments seriously affect patient’s life quality.If breast cancer can be detected in early stages and given effective treatment,it will most likely improve life quality as well as survival.Therefore,early diagnosis and timely treatment of breast cancer become urgent in breast cancer research.With the development of high-throughput sequencing technology,scientists have discovered a large number of circRNAs and demonstrated that circRNAs play important roles in cancer development.The high conservation,tissue specificity and stability of circRNAs make them potential diagnostic markers in cancer.In this study,a circular RNA,circFOXK2,was identfied through circRNA-seq to be highly expressed in MCF-7 cells,which was then validated in many other breast cancer cell lines.CircFOXK2 mainly existed in the cytoplasm and had significant effects on cell growth and cell cycle progression of MCF-7 cells as well as MCF7 xenograft growth in mice.RNA-seq analysis showed that knockdown of circFOXK2 led to the changes of thousands of genes involved in many biological pathways including cell cycle regulation.To understand the molecular mechanism underlying circFOXK2 function in breast cancer,we performed RNA pull-down experiments to identify proteins associated with circFOXK2.Preliminary analysis indicated that circFOXK2 interacted with the MCM family.To underscore the clinical significance of circFOXK2,it was found to be highly expressed in breast cancer,prostate cancer,esophageal cancer and colorectal cancer tissue samples and be required for the growth of cancer cells representing these cancer types.More importantly,anti-sense oligonucleotides(ASO)targeting circFOXK2 was effective in suppressing cancer cell growth.Our study revealed that circFOXK2 might serve as a diagnostic marker and therapeutic target for breast as well as other cancers.