Long Noncoding RNA TINCR-mediated Regulation of Acetyl-CoA Metabolism Promotes Nasopharyngeal Carcinoma Progression and Chemoresistance

Our present study showed that lncRNA TINCR have impact on the ubiquitination-mediated degradation level of ACLY protein in nasopharyngeal carcinoma. Silencing of TINCR lead to downregulation of ACLY protein level. ACLY is a cytosolic homotetrameric enzyme catalyzing the ATP-dependent conversion of citrate and coenzyme A (CoA) to oxaloacetate and acetyl-CoA, a precursor for lipid biosynthesis, including cholesterol, free fatty acid and phospholipid. Meanwhile, the cellular acetyl-CoA pool is also required for acetylation reactions that modify proteins such as histone acetylation, including Histone H3 acetylation K27 (H3K27ac). To select the shared genes that were regulated by TINCR and were in response to acetyl-CoA alteration, we conducted RNA-seq in HONE-1 cells with or without TINCR or ACLY silencing, as well as H3K27ac Chromatin Immunoprecipitation sequencing (ChIP-seq) in HONE-1 cells with or without ACLY silencing. We also performed CLIP-seq in HONE-1 and SUNE-1 cells to validate the TINCR-ACLY interaction and identify the binding sites of TINCR with ACLY. Overall design: We conducted RNA-seq in HONE-1 with or with out TINCR or ACLY silencing, H3K27ac Chromatin Immunoprecipitation sequencing (ChIP-seq) in HONE-1 cells with or without ACLY silencing, and ACLY crosslinking-immunprecipitation sequencing (CLIP-seq) in SUNE-1 and HONE-1 cells.