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长链非编码 RNA MRPL23-AS1 促进腺样囊性癌肺转移。

Long Noncoding RNA MRPL23-AS1 Promotes Adenoid Cystic Carcinoma Lung Metastasis.

机构信息

Central Laboratory, Peking University School and Hospital of Stomatology, Beijing, PR China.

National Clinical Research Center for Oral Diseases, Beijing, PR China.

出版信息

Cancer Res. 2020 Jun 1;80(11):2273-2285. doi: 10.1158/0008-5472.CAN-19-0819. Epub 2020 Feb 25.

Abstract

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.

摘要

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。

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