Yi Xie , Jindong Xie , Guoxian Huang , Jinhui Zhang , Cailu Song , Yongzhou Luo , Hailin Tang , Yuhui Tang , Xiangsheng Xiao , Chi Zhang , Zeyu Shuang , Xing Li
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引用次数: 0
Abstract
Brain metastasis (BM) is a serious complication of increasing incidence in patients with advanced breast cancer, which is characterized by swift deterioration in quality of life with few efficient therapy strategies. There is an urgent clinical requirement to devise potent therapeutic strategies for the prevention and management of brain metastases. Here, we report isoliquiritigenin (ISL), a key bioactive substance extracted from licorice root, which effectively inhibited triple-negative breast cancer (TNBC) brain metastasis (BM) by downregulation of circNAV3. CircRNAs expression analyses and functional studies, coupled with clinical significance investigations identified circNAV3 as a key molecule promoting TNBC BM. Functionally, circNAV3 could promote proliferation, migration, invasion, angiogenesis and capacity to penetrate the blood-brain barrier of TNBC cells. Mechanistically, circNAV3 could competitively bind with miR-4262, hence intercepting the suppressive effect of miR-4262 on ST6GALNAC5. Subsequently, this interplay enhanced EGFR sialylation and activation, initiating the PI3K/Akt pathway and ultimately fostering the development of TNBC brain metastases. In conclusion, our research establishes that ISL impede the initiation and advancement of TNBC brain metastasis by modulation of circNAV3/miR-4262/ST6GALNAC5/EGFR axis, laying a theoretical groundwork for the therapeutic use of ISL in this scenario.
期刊介绍:
Cancer Letters is a reputable international journal that serves as a platform for significant and original contributions in cancer research. The journal welcomes both full-length articles and Mini Reviews in the wide-ranging field of basic and translational oncology. Furthermore, it frequently presents Special Issues that shed light on current and topical areas in cancer research.
Cancer Letters is highly interested in various fundamental aspects that can cater to a diverse readership. These areas include the molecular genetics and cell biology of cancer, radiation biology, molecular pathology, hormones and cancer, viral oncology, metastasis, and chemoprevention. The journal actively focuses on experimental therapeutics, particularly the advancement of targeted therapies for personalized cancer medicine, such as metronomic chemotherapy.
By publishing groundbreaking research and promoting advancements in cancer treatments, Cancer Letters aims to actively contribute to the fight against cancer and the improvement of patient outcomes.