Long non-coding antisense RNA HYOU1-AS is essential to human breast cancer development through competitive binding hnRNPA1 to promote HYOU1 expression
Long non-coding antisense RNA HYOU1-AS is essential to human breast cancer development through competitive binding hnRNPA1 to promote HYOU1 expression
复制标题
长非编码反义RNA HYOU1-AS通过竞争性结合hnRNPA1促进HYOU1表达，对人类乳腺癌的发展至关重要
DOI：
10.1016/j.bbamcr.2021.118951
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发表时间：
2021-01-15
影响因子：
5.1
通讯作者：
Sui, Guangchao
中科院分区：
文献类型：
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作者：
Hao, Aixin;Wang, Yu;Sui, Guangchao
三阴性乳腺癌（TNBC）由于缺乏生物标志物和治疗靶点，预后较差。新兴研究表明，长链非编码rna （lncRNAs）参与乳腺癌的进展，但其功能和调控机制仍然知之甚少，特别是在TNBC中。在本研究中，我们对5例TNBC样本及其匹配的正常组织进行了lncRNA微阵列分析，发现了一些差异表达的lncRNA。我们发现了一个反义lncRNA， HYOU1- as，它是从缺氧上调1 （HYOU1）基因的另一条链转录而来，富集于细胞核中，在TNBC中高表达。HYOU1-AS敲低可抑制TNBC MDA-MB-231细胞的增殖和迁移，减少其在裸鼠体内异种移植瘤的形成。在机制研究中，我们发现HYOU1- as可通过与rna结合蛋白hnRNPA1竞争性结合，促进增殖基因HYOU1的表达，减轻其对HYOU1 mRNA转录后的抑制作用。根据我们对TCGA数据库的研究，HYOU1水平升高与乳腺癌患者临床预后不良相关。总的来说，我们的数据表明lncRNA HYOU1- as通过上调HYOU1促进TNBC的进展。
Triple negative breast cancer (TNBC) has poor prognosis due to lack of biomarker and therapeutic target. Emerging research has revealed long noncoding RNAs (lncRNAs) are involved in breast cancer progression, but their functions and regulatory mechanisms remain poorly understood, especially in TNBC. In this study, we performed lncRNA microarray analysis of five TNBC samples and their matched normal tissues, and discovered a number of differentially expressed lncRNAs. We identified an antisense lncRNA, HYOU1-AS, which is transcribed from the opposite strand of the hypoxia up-regulated 1 (HYOU1) gene, enriched in the nucleus and highly expressed in TNBC. HYOU1-AS knockdown could inhibit the proliferation and migration of the TNBC MDA-MB-231 cells, and reduce their xenograft tumor formation in nude mice. In mechanistic studies, we found that HYOU1-AS could promote the expression of HYOU1, a proliferative gene, through competitively binding to hnRNPA1, an RNA-binding protein, to relieve its post-transcriptional inhibition of the HYOU1 mRNA. Consistently, increased HYOU1 levels correlated with poor clinical outcomes of breast cancer patients based on our study of the TCGA database. Overall, our data indicated that the lncRNA HYOU1-AS promoted TNBC progression through upregulating HYOU1.