ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

文献类型： 外文期刊

第一作者： Zhu, Hui-er

作者： Zhu, Hui-er;Chen, De-xiong;Li, Tao;Shi, Shengnan;Chen, Weiping;Chen, Hui

作者机构：

关键词： Acetylation; Metabolism reprogramming; Lung adenocarcinoma; ESCO2; hnRNPA1

期刊名称：JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH （ 影响因子：11.161； 五年影响因子：9.976 ）

ISSN：

年卷期： 2021 年 40 卷 1 期

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收录情况： SCI

摘要： 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.

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