雌激素受体α及DNA结合域在宫颈病变中的研究进展

Progress of Estrogen Receptor α and Its DNA Binding Domain in Cervical Lesions

宫颈癌是一种发生在宫颈上皮的妇科恶性肿瘤,其是全球女性恶性肿瘤中最为常见的癌症之一。尽管采取各种预防措施,如HPV筛查和预防性HPV疫苗,在一定程度上降低了宫颈癌的发病率,但宫颈癌的转移和复发仍然是患者死亡的主要原因。除HPV感染外,雌激素及雌激素受体α(ERα)对宫颈病变的影响非常重要,同时,长期口服避孕药和多胎妊娠会增加宫颈癌发病的风险。越来越多研究表明,有多种miRNA参与调节ERα,进而促进宫颈癌的发生;且在宫颈癌中发现ESR1的突变,推测其参与着宫颈病变的发生与发展。转基因小鼠实验表明对ERαDNA结合域(DBD)的干扰可影响相关的基因转录,DBD区域突变的转基因鼠在雌激素作用下不会发生宫颈癌,因此,DBD区域可能成为宫颈病变早期诊断和临床治疗的新靶点。本文对ERα及其突变、miRNA调节以及DBD区域与宫颈病变相关方面的研究进展做一综述。

Cervical cancer is a gynecological malignancy that occurs in the cervical epithelium and ranks fourth among common malignancies in women. Despite various preventive measures, such as HPV screening and prophylactic HPV vaccines, which reduce the incidence of cervical cancer to some extent, metastasis and recurrence of cervical cancer remain the main cause of patient death. In addition to HPV infection, the effects of estrogen and estrogen receptor α(ERα) on cervical lesions are very important, and long-term oral contraceptives and multiple pregnancies increase the risk of cervical cancer. More and more studies have shown that a variety of miRNAs are involved in regulating ERα, which in turn promotes the occurrence of cervical cancer;and ESR1 mutations are found in cervical cancer, which are speculated to be involved in the occurrence and development of cervical lesions. Experiments in transgenic mice have shown that interference with the ERα DNA-binding domain(DBD) can affect the transcription of related genes, and transgenic mice with mutations in the DBD region do not develop cervical cancer under the action of estrogen, so the DBD region may become a new target for the early diagnosis and clinical treatment of cervical lesions. In this paper, we review the research progress of ERα and its mutations, miRNA regulation, and the correlation between DBD regions and cervical lesions.