Department of Oncology and Metabolism, Medical School, University of Sheffield, Sheffield, UK.
INSERM, Research Unit UMR_S1033, LyOS, Faculty of Medicine Lyon-Est, Lyon, France.
Br J Cancer. 2023 Sep;129(5):754-771. doi: 10.1038/s41416-023-02340-9. Epub 2023 Jul 13.
Breast cancer (BC) metastasis, which often occurs in bone, contributes substantially to mortality. MicroRNAs play a fundamental role in BC metastasis, although microRNA-regulated mechanisms driving metastasis progression remain poorly understood.
MiRome analysis in serum from BC patients was performed by TaqMan™ low-density array. MiR-662 was overexpressed following MIMIC-transfection or lentivirus transduction. Animal models were used to investigate the role of miR-662 in BC (bone) metastasis. The effect of miR-662-overexpressing BC cell conditioned medium on osteoclastogenesis was investigated. ALDEFLUOR assays were performed to study BC stemness. RNA-sequencing transcriptomic analysis of miR-662-overexpressing BC cells was performed to evaluate gene expression changes.
High levels of hsa-miR-662 (miR-662) in serum from BC patients, at baseline (time of surgery), were associated with future recurrence in bone. At an early-stage of the metastatic disease, miR-662 could mask the presence of BC metastases in bone by inhibiting the differentiation of bone-resorbing osteoclasts. Nonetheless, metastatic miR-662-overexpressing BC cells then progressed as overt osteolytic metastases thanks to increased stem cell-like traits.
MiR-662 is involved in BC metastasis progression, suggesting it may be used as a prognostic marker to identify BC patients at high risk of metastasis.
乳腺癌（BC）转移，常发生于骨，对死亡率有重大影响。微小 RNA 在 BC 转移中起重要作用，尽管微小 RNA 调控的转移进展机制仍知之甚少。
通过 TaqMan™ 低密度阵列对 BC 患者血清进行 MiRome 分析。MIMIC 转染或慢病毒转导后过表达 miR-662。动物模型用于研究 miR-662 在 BC（骨）转移中的作用。研究 miR-662 过表达 BC 细胞条件培养基对破骨细胞形成的影响。通过 ALDEFLUOR 测定法研究 BC 干性。对 miR-662 过表达 BC 细胞进行 RNA 测序转录组分析，以评估基因表达变化。
BC 患者基线（手术时）血清中高水平的 hsa-miR-662（miR-662）与未来骨转移复发相关。在疾病的早期转移阶段，miR-662 可通过抑制骨吸收破骨细胞的分化来掩盖骨转移的存在。然而，转移性 miR-662 过表达 BC 细胞随后进展为明显的溶骨性转移，这要归功于增加的干细胞样特征。
miR-662 参与 BC 转移进展，表明它可用作预后标志物，以识别高转移风险的 BC 患者。
