POTENTIAL ROLE OF CARBOHYDRATE RESPONSE ELEMENT BINDING PROTEIN IN NON-SMALL CELL LUNG CANCER
Carbohydrate response element binding protein (ChREBP) is a transcription factor that plays crucial roles in major tissues involved in metabolism. Evidence indicates that ChREBP may have roles in cancer. The presence and function of ChREBP have never been identified in non-small cell lung cancer (NSCLC).
We investigated ChREBP expression in NCI-H1975 NSCLC cell line using reverse transcription quantitative PCR. To study ChREBP loss-of-function, we constructed Doxycycline-inducible lentiviral vector containing dominant negative ChREBP or nuclear form of enhanced yellow fluorescent protein. RNA samples from induced cell lines were subjected to RNA sequencing.
Both alpha and beta isoforms of ChREBP are present in NCI-H1975 cells. Inhibition of ChREBP function using dominant negative form of ChREBP leads to downregulation of 1,210 genes and upregulation of 188 genes as compared to control. Gene set enrichment analysis reveals the potential function of ChREBP to control expression of genes involved in several pathways, including interferon response, NFKB response to TNF, and complement signaling pathway. Interestingly, expression of 51 genes in epithelial-to-mesenchymal transition (EMT) pathway was altered. The EMT markers, vimentin/E-cadherin expression ratio and ZEB1 expression, were decreased.
Our study is first to demonstrate expression of both ChREBP isoforms in NSCLC cell line. We also identify several pathways regulated by this transcription factor. Further study is needed to explore the role of ChREBP in EMT in NSCLC.