ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

Abstract

Background Emerging evidence indicates that metabolism reprogramming and abnormal acetylation modification play an important role in lung adenocarcinoma (LUAD) progression, although the mechanism is largely unknown. Methods Here, we used three public databases (Oncomine, Gene Expression Omnibus [GEO], The Cancer Genome Atlas [TCGA]) to analyze ESCO2 (establishment of cohesion 1 homolog 2) expression in LUAD. The biological function of ESCO2 was studiedusing cell proliferation, colony formation, cell migration, and invasion assays in vitro, and mouse xenograft models in vivo. ESCO2 interacting proteins were searched using gene set enrichment analysis (GSEA) and mass spectrometry. Pyruvate kinase M1/2 (PKM) mRNA splicing assay was performed using RT-PCR together with restriction digestion. LUAD cell metabolism was studied using glucose uptake assays and lactate production. ESCO2 expression was significantly upregulated in LUAD tissues, and higher ESCO2 expression indicated worse prognosis for patients with LUAD. Results We found that ESCO2 promoted LUAD cell proliferation and metastasis metabolic reprogramming in vitro and in vivo. Mechanistically, ESCO2 increased hnRNPA1 (heterogeneous nuclear ribonucleoprotein A1) binding to the intronic sequences flanking exon 9 (EI9) of PKM mRNA by inhibiting hnRNPA1 nuclear translocation, eventually inhibiting PKM1 isoform formation and inducing PKM2 isoform formation. Conclusions Our findings confirm that ESCO2 is a key factor in promoting LUAD malignant progression and suggest that it is a new target for treating LUAD.

Long noncoding RNA ZMIZ1‐AS1 promotes gefitinib resistance via binding to hnRNPA1

“…[11][12][13] hnRNPA1 has been reported to participate in multiple molecular events in cancer transformation. [14][15][16] Here, we reported that ZMIZ1-AS1 binded to hnRNPA1 by RNA pull-down assay and mass spectrometry. Our study has limitations because we did not reveal how ZMIZ1-AS1 promoted gefitinib resistance by combining with hnRNPA1.…”

The Prognostic Value of Lysine Acetylation Regulators in Hepatocellular Carcinoma

“…The role of ESCO2 in HCC has not yet been reported. However, ESCO2 promotes proliferation and metastatic metabolic reprogramming of lung adenocarcinoma cells in vitro and in vivo ( Zhu et al, 2021 ). Moreover, ESCO2 knockdown inhibits cell proliferation and induces apoptosis in human gastric cancer cells ( Chen et al, 2018 ).…”

hnRNP A/B Proteins: An Encyclopedic Assessment of Their Roles in Homeostasis and Disease

“…In these instances, both A1 and A2/B1 specifically recognize a G-quadruplex structure, like that in telomeric DNA, in many of the promoter regions they regulate [ 68 , 69 , 70 , 71 ]. A1 and A2/B1 are found to be overexpressed in a number of cancers [ 63 , 72 , 73 , 74 , 75 ]. This is characterized to result in an aberrant up-regulation of transcriptional targets like TRA2B (encoding Transformer 2β) in colon cancer [ 68 ] or KRAS (encoding Kirsten rat sarcoma viral oncogene homolog) in pancreatic cancer [ 69 , 71 ].…”