Hu Yixuan, Bian Jin, Chen Weiwei, Shi Junfeng, Wei Xiaowei, Du Yueyao, Zhang Wenwen
Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Department of Medical Oncology of PLA Cancer Center, Jinling Hospital, Nanjing, China.
J Biol Chem. 2025 Apr;301(4):108428. doi: 10.1016/j.jbc.2025.108428. Epub 2025 Mar 19.
Our previous study showed that androgen receptor (AR) promotes triple-negative breast cancer (TNBC) cell tumorigenesis, but the underlying mechanisms remain unclear. Herein, using microarray analysis of long noncoding RNA expression profiles, we identified an AR-related long noncoding RNA SOX2-OT in TNBC. We found that AR could promote TNBC tumorigenesis by acting as a transcription factor to activate the expression of SOX2-OT. Mechanistic analysis demonstrated that SOX2-OT serves as a molecular sponge for miR-320a-5p to regulate the expression of CCR5. In addition, SOX2-OT promotes TNBC cell proliferation and inhibits apoptosis in an miR-320a-5p-dependent manner. Using a xenograft mouse model, we found that SOX2-OT-CCR5 axis could promote TNBC tumorigenesis in vivo. Importantly, the AR-SOX2-OT-miR-320a-5p-CCR5 axis is manifested in the tissues of 165 TNBC patients. Collectively, our results suggest that SOX2-OT can regulate AR-induced TNBC tumorigenesis through the miR-320a-5p-CCR5 signaling axis and reveal the great potential of targeting SOX2-OT for the treatment of TNBC patients.
我们之前的研究表明，雄激素受体（AR）可促进三阴性乳腺癌（TNBC）细胞的肿瘤发生，但其潜在机制仍不清楚。在此，通过对长链非编码RNA表达谱进行微阵列分析，我们在TNBC中鉴定出一种与AR相关的长链非编码RNA SOX2-OT。我们发现，AR可作为转录因子激活SOX2-OT的表达，从而促进TNBC的肿瘤发生。机制分析表明，SOX2-OT作为miR-320a-5p的分子海绵来调节CCR5的表达。此外，SOX2-OT以miR-320a-5p依赖的方式促进TNBC细胞增殖并抑制细胞凋亡。利用异种移植小鼠模型，我们发现SOX2-OT-CCR5轴可在体内促进TNBC的肿瘤发生。重要的是，AR-SOX2-OT-miR-320a-5p-CCR5轴在165例TNBC患者的组织中得到证实。总体而言，我们的结果表明，SOX2-OT可通过miR-320a-5p-CCR5信号轴调节AR诱导的TNBC肿瘤发生，并揭示了靶向SOX2-OT治疗TNBC患者的巨大潜力。
