ILF2 cooperates with E2F1 to maintain mitochondrial homeostasis and promote small cell lung cancer progression

Meng Zhao, Yahui Liu, Jiao Chang, et al.

Abstract


Objective: Mitochondria play multifunctional roles in carcinogenesis. Deciphering uncertainties of molecular interactions withinmitochondria will promote further understanding of cancer. Interleukin enhancer binding factor 2 (ILF2) is upregulated in severalmalignancies, however, much remains unknown regarding ILF2 in small cell lung cancer (SCLC). In the current study, weexplored 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 onSCLC progression. Glucose uptake, lactate production, cellular oxygen consumption rate and extracellular acidification rate weremeasured 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 mitochondrialmembrane 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 declinesglucose intake and lactate production. Genome-wide analysis of ILF2 targets identified a cohort of genes regulated by E2F1. Inconsistent with this, we found ILF2 interacts with E2F1 in SCLC cells. Further studies demonstrated that suppression of E2F1expression could reverse ILF2-induced tumor growth and enhanced mitochondria function. Significantly, expression of ILF2 isprogressively increase during SCLC progression and high ILF2 expression is correlated with higher histologic grades, whichindicates ILF2’s oncogenic role in SCLC.

Conclusions: Our results demonstrate that ILF2 interacts with E2F1 to maintain mitochondria quality and confers SCLC cellsgrowth advantage in tumorigenesis.

Cite this article as: Zhao M, Liu Y, Chang J, Qi J, Liu R, Hou Y, et al. ILF2cooperates with E2F1 to maintain mitochondrial homeostasis and promotesmall cell lung cancer progression. Cancer Biol Med. 2019; 16: 771-83. doi:10.20892/j.issn.2095-3941.2019.0050


Keywords


E2F1; OXPHOS; mitochondria; metabolism; SCLC

Full Text: PDF HTML

Refbacks

  • There are currently no refbacks.



OUR FRIENDS