DEAD-box helicase 5 (DDX5) is a founding member of the DEAD-box RNA helicase family, a group of enzymes that regulate ribonucleoprotein formation and function in every aspect of RNA metabolism, ranging from synthesis to decay. Our laboratory previously found that DDX5 is involved in energy homeostasis, a process that is altered in many cancers. Small cell lung cancer (SCLC) is an understudied cancer type for which effective treatments are currently unavailable. Using an array of methods, including short hairpin RNA–mediated gene silencing, RNA and ChIP sequencing analyses, and metabolite profiling, we show here that DDX5 is overexpressed in SCLC cell lines and that its down-regulation results in various metabolic and cellular alterations. Depletion of DDX5 resulted in reduced growth and mitochondrial dysfunction in the chemoresistant SCLC cell line H69AR. The latter was evidenced by down-regulation of genes involved in oxidative phosphorylation and by impaired oxygen consumption. Interestingly, DDX5 depletion specifically reduced intracellular succinate, a TCA cycle intermediate that serves as a direct electron donor to mitochondrial complex II. We propose that the oncogenic role of DDX5, at least in part, manifests as up-regulation of respiration supporting the energy demands of cancer cells.

中文翻译：

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RNA 解旋酶 DDX5 支持小细胞肺癌中的线粒体功能。

DEAD-box 解旋酶 5 (DDX5) 是 DEAD-box RNA 解旋酶家族的创始成员，该家族是一组调节核糖核蛋白形成以及在 RNA 代谢各个方面（从合成到衰变）发挥作用的酶。我们的实验室之前发现 DDX5 参与能量稳态，这一过程在许多癌症中都会发生改变。小细胞肺癌（SCLC）是一种尚未得到充分研究的癌症类型，目前尚无有效的治疗方法。使用一系列方法，包括短发夹 RNA 介导的基因沉默、RNA 和 ChIP 测序分析以及代谢物分析，我们在此表明​​ DDX5 在 SCLC 细胞系中过度表达，并且其下调会导致各种代谢和细胞改变。DDX5 的耗竭导致化疗耐药 SCLC 细胞系 H69AR 的生长减少和线粒体功能障碍。后者的证据是参与氧化磷酸化的基因下调和耗氧量受损。有趣的是，DDX5 消耗特异性地减少了细胞内琥珀酸，这是一种 TCA 循环中间体，可作为线粒体复合物 II 的直接电子供体。我们认为，DDX5 的致癌作用至少部分表现为上调呼吸作用，支持癌细胞的能量需求。一种 TCA 循环中间体，作为线粒体复合物 II 的直接电子供体。我们认为，DDX5 的致癌作用至少部分表现为上调呼吸作用，支持癌细胞的能量需求。一种 TCA 循环中间体，作为线粒体复合物 II 的直接电子供体。我们认为，DDX5 的致癌作用至少部分表现为上调呼吸作用，支持癌细胞的能量需求。