DICER1
小结
DICER1是抑癌基因，编码蛋白是一种内切核糖核酸酶，催化大RNA分子裂解成沉默RNA或microRNA。此外，DICER1将siRNA加载到Argonaute蛋白上并介导辅因子的结合以启动RNA诱导的沉默。DICER1以这种方式在基因表达的转录后调节中起关键作用。DICER1胚系突变与家族性肿瘤易感综合征相关，该综合征最常见的是会增加胸膜肺母细胞瘤（PPB）、囊性肾瘤（CN）、横纹肌肉瘤（RMS）、多结节性甲状腺肿、卵巢间质细胞瘤和其它肿瘤情况的风险。DICER1的胚系突变大多是是无义、移码或剪接位点突变，导致过早的蛋白质截短和蛋白质功能的丧失。DICER1体细胞突变主要影响介导DICER1与miRNAs相互作用的蛋白质区域。DICER1已被鉴定为单倍体不足的肿瘤抑制基因，DICER1的双等位基因丢失导致肿瘤形成。与DICER1作为肿瘤抑制因子的作用一致，DICER1的表达水平降低与肺癌、乳腺癌、皮肤癌、子宫内膜癌和卵巢癌的不良预后有关。
DICER1 is an endoribonuclease that catalyzes the cleavage of large RNA molecules into silencing RNAs or microRNAs. In addition, DICER1 loads siRNA onto the Argonaute protein and mediates the binding of co-factors to initiate RNA-induced silencing. In this way, DICER1 plays a pivotal role in the post-transcriptional regulation of gene expression. Germline mutations in DICER1 are associated with DICER1-related disorders, a familial tumor susceptibility syndrome that confers increased risk most commonly for pleuropulmonary blastoma (PPB), cystic nephroma (CN), rhabdomyosarcoma (RMS), multinodular goiter, ovarian Sertoli-Leydig cell tumor and other neoplastic condition. The majority of germline mutations in DICER1 are nonsense, frameshift, or splice-site mutations leading to premature protein truncation and loss of protein function. Somatic DICER1 mutations have also been identified, predominantly affecting the region of the protein that mediates the interaction of DICER1 with miRNAs. DICER1 has been identified as a haploinsufficient tumor suppressor gene , as monoallelic but biallelic loss of DICER1 causes tumor formation. Consistent with the role of DICER1 as a tumor suppressor, reduced expression of DICER1 correlates with a poor outcome in lung, breast, skin, endometrial and ovarian cancer.