MicroRNA-223 Increases the Sensitivity of Triple-Negative Breast Cancer Stem Cells to TRAIL-Induced Apoptosis by Targeting HAX-1.
Drug resistance remains a significant challenge in the treatment of triple-negative breast cancer (TNBC). Recent studies have demonstrated that this drug resistance is associated with a group of cells known as cancer stem cells (CSCs), which are believed to determine the sensitivity of tumor cells to cancer treatment. MicroRNAs (miRNAs) are small, non-coding RNAs that play significant roles in normal and cancer cells. MiR-223 reportedly acts as a tumor suppressor in a range of cancers. However, the role of miR-223 in TNBC, especially in triple-negative breast cancer stem cells (TNBCSCs), remains unknown. Here, we found that miR-223 expression was down-regulated in CD44+CD24-/low TNBCSCs compared with non-CSCs. Furthermore, we found that miR-223 overexpression resensitized TNBCSCs to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis. The HAX-1 gene, which is located in the mitochondria and functions as an anti-apoptotic protein, was found to be directly regulated by miR-223 in MDA-MB-231 cells. We demonstrated that miR-223 overexpression promoted TRAIL-induced apoptosis through the mitochondria/ROS pathway. In conclusion, our results suggest that miR-223 increases the sensitivity of TNBCSCs to TRAIL-induced apoptosis by targeting HAX-1. Our findings have improved our understanding of the role of miR-223 in TNBC and may contribute to TNBC treatment.
Department of Gastrointestinal Surgery, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, 250117, China.
Xu
X
Sun
Breast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Shandong Academy of Medical Sciences, Jinan, 250117, China.
Yongqing
Y
Li
Breast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Shandong Academy of Medical Sciences, Jinan, 250117, China.
Meizhu
M
Zheng
Breast Cancer Center, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Shandong Academy of Medical Sciences, Jinan, 250117, China.
Wenshu
W
Zuo
Emergency Medicine, Jinan Lixia District People's Hospital, Jinan, 250000, China.
Wenzhu
W
Zheng
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000502:physiology*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D015536:Down-Regulation; D004317:Doxorubicin / Q000627:therapeutic use; D006801:Humans; D035683:MicroRNAs / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000502:physiology*; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D020169:Caspases; D002945:Cisplatin; D004317:Doxorubicin; D035683:MicroRNAs; D053221:TNF-Related Apoptosis-Inducing Ligand; C104759:HAX1 protein, human; C525067:MIR223, human