文章目录

正-反义RNA相互作用通过调控NQO1表达促进乳腺癌转移

原文发布日期：2023-05-11

英文摘要：

摘要翻译：

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文章：

正-反义RNA相互作用通过调控NQO1表达促进乳腺癌转移

A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression

原文发布日期：2023-05-11

英文摘要：

Antisense RNAs are ubiquitous in human cells, yet their role is largely unexplored. Here we profiled antisense RNAs in the MDA-MB-231 breast cancer cell line and its highly lung metastatic derivative. We identified one antisense RNA that drives cancer progression by upregulating the redox enzyme NADPH quinone dehydrogenase 1 (NQO1), and named it NQO1-AS. Knockdown of either NQO1 or NQO1-AS reduced lung colonization in a mouse model, and investigation into the role of NQO1 indicated that it is broadly protective against oxidative damage and ferroptosis. Breast cancer cells in the lung are dependent on this pathway, and this dependence can be exploited therapeutically by inducing ferroptosis while inhibiting NQO1. Together, our findings establish a role for NQO1-AS in the progression of breast cancer by regulating its sense mRNA post-transcriptionally. Because breast cancer predominantly affects females, the disease models used in this study are of female origin and the results are primarily applicable to females.

摘要翻译：

反义RNA普遍存在于人体细胞中，然而它们的作用却一直未被充分阐明。本研究对MDA-MB-231乳腺癌细胞系及其具有高度肺癌转移特性的变异体进行了表型分析，揭示了一种通过上调NADPH quinone dehydrogenase 1（NQO1）酶活性从而推动肿瘤进展的反义RNA，并将其命名为NQO1-AS。我们发现，在小鼠模型中，NQO1或NQO1-AS抑制均降低了肺癌转移，同时研究NQO1的机制表明其广泛地保护细胞免受氧化损伤和铁凋亡的影响。在肺癌中，乳腺癌细胞依赖于该通路，这可以通过诱导铁凋亡的同时抑制NQO1加以药物治疗。综上所述，我们的发现揭示了NQO1-AS在乳腺癌进展中的作用，并证明其通过调控其对应的编码mRNA实现的转录后调控。由于乳腺癌主要影响女性，因此本研究中采用的疾病模型具有雌性特征，且结果主要适用于女性患者。