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他莫昔芬,作为一种抗雌激素治疗剂,临床上广泛用于治疗雌激素受体阳性(ER+)乳腺癌患者。然而,他莫昔芬耐药性的产生成为乳腺癌治疗的主要障碍,因此充分了解他莫昔芬耐药的机制显得尤为重要。他莫昔芬耐药产生的机制包括:他莫昔芬药理学机制;ERα表达缺失、突变或翻译后修饰;共调节蛋白的失衡以及不同信号转导途径的变化。micro RNA(mi RNA),是一类非编码微小RNA分子,可调控其相关靶向m RNA的表达,参与肿瘤的发生、发展、生长抑制、凋亡等过程的分子调控。因此,可依据特定mi RNA表达谱判断肿瘤的状况或诊断。简单论述雌激素和他莫昔芬的作用机制,着重讨论了参与调控人乳腺癌他莫昔芬耐药的mi RNA及其调控的具体机制。目前已经鉴定了许多与乳腺癌他莫昔芬耐药相关的mi RNA,这对于研发治疗乳腺癌他莫昔芬耐药的新型mi RNA提供了思路和方法。
Tamoxifen, as an anti-estrogen therapeutic, is clinically widely used in patients with estrogen receptor-positive (ER +) breast cancer. However, the development of tamoxifen resistance is a major obstacle to the treatment of breast cancer, so it is important to fully understand the mechanism of tamoxifen resistance. Mechanisms involved in tamoxifen resistance include: tamoxifen pharmacological mechanisms; deletion of ERα expression, mutations or post-translational modifications; co-regulation of protein imbalances and changes in different signal transduction pathways. Micro RNA (miRNA), a class of non-coding microRNA molecules, regulates the expression of related target m RNAs and is involved in the molecular regulation of tumorigenesis, development, growth inhibition and apoptosis. Therefore, the status or diagnosis of the tumor can be judged based on the specific miRNA expression profile. The mechanism of action of estrogen and tamoxifen is briefly discussed, and the specific mechanism of miRNAs involved in the regulation of tamoxifen resistance in human breast cancer and its regulation are discussed. So far, many miRNAs have been identified that are associated with resistance to tamoxifen in breast cancer. This has provided insights into the development of novel miRNAs that are resistant to tamoxifen in breast cancer.