Highlights d Quantitative acetylomics reveals hyperacetylated proteins upon nutrition starvation d Multiple cellular stresses result in p300-dependent PHF5A K29 acetylation d PHF5A K29 acetylation enhances KDM3A expression by stabilizing its mRNA d PHF5A acetylation and KDM3A upregulation predict poor prognosis in colon cancer

Protein lysine acetylation affects colorectal cancer (CRC) distant metastasis through multiple pathways. In a previous proteomics screen, we found that isocitrate dehydrogenase 1 (IDH1) is hyperacetylated in CRC primary tumors and liver metastases. Here, we further investigate the function of IDH1 hyperacetylation at lysine 224 in CRC progression. We find that IDH1 K224 deacetylation promotes its enzymatic activity and the production of α‐KG, and we identify sirtuin‐2 (SIRT2) as a major deacetylase for IDH1. SIRT2 overexpression significantly inhibits CRC cell proliferation, migration, and invasion. IDH1 acetylation is modulated in response to intracellular metabolite concentration and regulates cellular redox hemostasis. Moreover, IDH1 acetylation reversely regulates HIF1α‐dependent SRC transcription which in turn controls CRC progression. Physiologically, our data indicate that IDH1 deacetylation represses CRC cell invasion and migration in vitro and in vivo, while the hyperacetylation of IDH1 on K224 is significantly correlated to distant metastasis and poor survival of colorectal cancer patients. In summary, our study uncovers a novel mechanism through which SIRT2‐dependent IDH1 deacetylation regulates cellular metabolism and inhibits liver metastasis of colorectal cancer.

Colon cancer-associated transcript-1 (CCAT1) is a highly conserved long noncoding RNA that is deregulated in several cancers. However, its role in gastric carcinoma and its posttranscriptional regulation remain poorly understood. In this study, we provide the first evidence that CCAT1 regulates miR-490 in gastric cancer (GC) cells. Interestingly, miR-490 can also repress CCAT1 expression. CCAT1 expression was significantly upregulated, and miR-490 expression was downregulated in GC. The negative correlation between miR-490 and CCAT1 expression was observed in GC tissues. Importantly, CCAT1 contains a putative miR-490-binding site, and deletion of this binding site abolishes their miR-490 responsiveness.Post-transcriptional CCAT1 silencing by miR-490 significantly suppressed GC cell migration. Furthermore, miR-490 directly bound to the hnRNPA1 mRNA 3 0 -UTR to repress its translation. Inhibition of miR-490 rescued CCAT1 siRNA-mediated suppression of cell migration. hnRNPA1 expression was significantly upregulated in GC specimens, and there was a negative correlation between miR-490 and hnRNPA1 expression and also a positive correlation between hnRNAP1 expression level and CCAT1 level. Taken together, we show for the first time that the CCAT1/miR-490/hnRNPA1 axis promotes GC migration, and it may have a possible diagnostic and therapeutic potential in GC. V C 2016 IUBMB Life, 68(3): [201][202][203][204][205][206][207][208][209][210] 2016

Deposition of amyloid β protein (Aβ) to form neuritic plaques in the brain is the unique pathological hallmark of Alzheimer's disease (AD). Aβ is derived from amyloid β precursor protein (APP) by β- and γ-secretase cleavages and turned over by glia in the central nervous system (CNS). Vitamin A deficiency (VAD) has been shown to affect cognitive functions. Marginal vitamin A deficiency (MVAD) is a serious and widespread public health problem among pregnant women and children in developing countries. However, the role of MVAD in the pathogenesis of AD remains elusive. Our study showed that MVAD is approximately twofold more prevalent than VAD in the elderly, and increased cognitive decline is positively correlated with lower VA levels. We found that MVAD, mostly prenatal MVAD, promotes beta-site APP cleaving enzyme 1 (BACE1)-mediated Aβ production and neuritic plaque formation, and significantly exacerbates memory deficits in AD model mice. Supplementing a therapeutic dose of VA rescued the MVAD-induced memory deficits. Taken together, our study demonstrates that MVAD facilitates AD pathogenesis and VA supplementation improves cognitive deficits. These results suggest that VA supplementation might be a potential approach for AD prevention and treatment.