Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China.
National Clinical Research Center for Oral Diseases, Beijing, PR China.
Cancer Res. 2020 Jun 1;80(11):2273-2285. doi: 10.1158/0008-5472.CAN-19-0819. Epub 2020 Feb 25.
Lung metastasis is a major factor affecting long-term survival in patients with adenoid cystic carcinoma. Here, we showed that the long noncoding RNA (lncRNA) MRPL23 antisense RNA 1 (MRPL23-AS1) was highly expressed and correlated with lung metastasis and overall survival in patients with salivary adenoid cystic carcinoma (SACC). MRPL23-AS1 positively regulated epithelial-mesenchymal transition by forming an RNA-protein complex with enhancer of zeste homolog 2 (EZH2). MRPL23-AS1 increased the binding of EZH2 and H3K27me3 on the E-cadherin promoter region. Moreover, MRPL23-AS1 levels were higher in exosomes isolated from the blood plasma of patients with SACC, and exosomal MRPL23-AS1 affected pulmonary microvascular endothelial cells in an "exosomecrine" manner. MRPL23-AS1-enriched exosomes increased microvascular permeability and facilitated the metastasis of SACC . Collectively, these findings highlight a molecular mechanism of lung metastasis in SACC. MRPL23-AS1 may represent a biomarker and target for clinical intervention to control this intractable disease. SIGNIFICANCE: This study identifies a novel metastasis-promoting lncRNA MRPL23-AS1, which mediates the transcriptional silencing of E-cadherin through forming an RNA-protein complex with EZH2.
肺转移是影响腺样囊性癌患者长期生存的主要因素。在这里,我们表明长链非编码 RNA (lncRNA) MRPL23 反义 RNA 1 (MRPL23-AS1) 在唾液腺癌 (SACC) 患者中高度表达,并与肺转移和总生存相关。MRPL23-AS1 通过与增强子结合抑制因子 2 (EZH2) 形成 RNA-蛋白质复合物,正向调节上皮-间充质转化。MRPL23-AS1 增加了 EZH2 和 H3K27me3 在 E-钙粘蛋白启动子区域的结合。此外,从 SACC 患者血浆中分离的外体中 MRPL23-AS1 水平较高,外体 MRPL23-AS1 以“外泌体分泌”的方式影响肺微血管内皮细胞。MRPL23-AS1 富集的外体增加了微血管通透性,并促进了 SACC 的转移。总之,这些发现强调了 SACC 肺转移的分子机制。MRPL23-AS1 可能代表一种生物标志物和临床干预靶点,以控制这种难治性疾病。意义:本研究鉴定了一种新型的促进转移的 lncRNA MRPL23-AS1,它通过与 EZH2 形成 RNA-蛋白质复合物,介导 E-钙粘蛋白的转录沉默。