Establishment of cohesion 1 homolog 2 facilitates cell aggressive behaviors and induces poor prognosis in renal cell carcinoma

Shi³

et al. 2021

Preprint

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.

Section: Discussionsupporting

confidence: 72%

Section: Introductionmentioning

confidence: 99%

ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

Shi³

et al. 2021

Preprint

“…Chen et al discovered that ESCO2 knockdown dramatically inhibited cell proliferation and induced apoptosis in human gastric cancer cells, and suppressed tumor xenograft development in vivo [ 19 ]. In addition, significantly high ESCO2 expression was found in renal cell carcinoma tissue and cell lines, promoting cell aggressive behaviors and inducing poor prognosis [ 15 ]. Therefore, together with other research data, our data indicate that ESCO2 plays a key role in the proliferation and metastasis of many types of human cancer.…”

Section: Discussionmentioning

confidence: 99%

“…In recent years, ESCO2 has been identified as an essential factor in cancer progression in multiple human cancers [ 14 – 17 ]. Compared with conventional chemotherapy, ESCO2 may become a more promising option for renal cell carcinoma treatment intervention [ 15 ]. ESCO2 is highly expressed in aggressive melanomas and breast cancer [ 16 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

Shi

et al. 2021

J Exp Clin Cancer Res

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.

“…In recent years, ESCO2 has been identi ed as an essential factor in cancer progression in multiple human cancers [13][14][15][16]. ESCO2 may be a promising option for renal cell carcinoma therapeutic interference, exhibiting enhanced selectivity over conventional chemotherapy [17]. ESCO2 is highly expressed in aggressive melanomas and breast cancer [15,18].…”

Section: Establishment Of Cohesion 1 Homolog 2 (Esco2) Is An Evolutiomentioning

confidence: 99%

ESCO2 promotes lung adenocarcinoma progression by regulating hnRNPA1 acetylation

Shi³

et al. 2020

Preprint

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 studied using 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.