ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression
ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression
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ILF2与E2F1合作维持线粒体稳态并促进小细胞肺癌进展。
DOI：
10.20892/j.issn.2095-3941.2019.0050
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发表时间：
2019-11-01
影响因子：
5.5
通讯作者：
Ren, Li
中科院分区：
文献类型：
--
作者：
Zhao, Meng;Liu, Yahui;Ren, Li
目的：线粒体在肿瘤发生过程中发挥多功能作用。破译线粒体内分子相互作用的不确定性将促进对癌症的进一步理解。白细胞介素增强子结合因子2（ILF2）在几种恶性肿瘤中上调，然而，关于ILF2在小细胞肺癌（SCLC）中的作用仍有许多未知之处。在目前的研究中，我们探讨了ILF2在小细胞肺癌中的作用，并证明了其在线粒体quality control.Methods的重要性：集落形成，细胞增殖，细胞活力和异种移植研究进行检查ILF2的作用，小细胞肺癌进展。测定葡萄糖摄取、乳酸产生、细胞耗氧速率和胞外酸化速率，以检查ILF 2对葡萄糖代谢的影响。利用RNA测序来探索由ILF2调控的基因。通过双荧光素酶报告基因测定来确定E2F1转录活性。进行线粒体定量和线粒体膜电位测定以检查线粒体质量。结果：ILF2在体内外均能促进SCLC肿瘤的生长。ILF2提高氧化磷酸化表达并降低葡萄糖摄入和乳酸产生。对ILF2靶点的全基因组分析鉴定了一组由E2F1调控的基因。与此一致，我们发现ILF2与E2F1在SCLC细胞中相互作用。进一步的研究表明，抑制E2F1表达可以逆转ILF2诱导的肿瘤生长并增强线粒体功能。值得注意的是，ILF2的表达在SCLC进展过程中逐渐增加，ILF2的高表达与较高的组织学分级相关，这表明ILF2在SCLC.Conclusions中的致癌作用：我们的研究结果表明，ILF2与E2F1相互作用，以维持线粒体质量，并赋予SCLC细胞在肿瘤发生中的生长优势。
Objective: Mitochondria play multifunctional roles in carcinogenesis. Deciphering uncertainties of molecular interactions within mitochondria will promote further understanding of cancer. Interleukin enhancer binding factor 2 (ILF2) is upregulated in several malignancies, however, much remains unknown regarding ILF2 in small cell lung cancer (SCLC). In the current study, we explored ILF2's role in SCLC and demonstrated its importance in mitochondria quality control.Methods: Colony formation, cell proliferation, cell viability and xenograft studies were performed to examine ILF2's role on SCLC progression. Glucose uptake, lactate production, cellular oxygen consumption rate and extracellular acidification rate were measured to examine the effect of ILF2 on glucose metabolism. RNA-sequencing was utilized to explore genes regulated by ILF2. E2F1 transcriptional activity was determined by dual luciferase reporter assay. Mitochondria quantification and mitochondrial membrane potential assays were performed to examine mitochondrial quality. Gene expression was determined by RT-qPCR, western blotting and IHC assay.Results: ILF2 promotes SCLC tumor growth in vitro and in vivo. ILF2 elevates oxidative phosphorylation expression and declines glucose intake and lactate production. Genome-wide analysis of ILF2 targets identified a cohort of genes regulated by E2F1. In consistent with this, we found ILF2 interacts with E2F1 in SCLC cells. Further studies demonstrated that suppression of E2F1 expression could reverse ILF2-induced tumor growth and enhanced mitochondria function. Significantly, expression of ILF2 is progressively increase during SCLC progression and high ILF2 expression is correlated with higher histologic grades, which indicates ILF2's oncogenic role in SCLC.Conclusions: Our results demonstrate that ILF2 interacts with E2F1 to maintain mitochondria quality and confers SCLC cells growth advantage in tumorigenesis.