RNA-Binding Protein Trx regulates alternative splicing and promotes metastasis of HCC via interacting with LINC00152
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ABSTRACT:
PROVIDER: PRJNA1029032 | ENA |
REPOSITORIES: ENA
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Project description:RNA-binding proteins (RBPs) were reported to be the key regulator of epithelial-mesenchymal transition (EMT)-related post-transcriptional in tumor diseases.To explore the role of RBPs in metastasis of hepatocellular To explore the role of RBPs in metastasis of hepatocellular carcinoma (HCC), whole transcription sequencing was conducted to identify differential RBPs between HCC with metastasis or without metastasis. The influence of RBPs on metastasis of HCC was verified by in vitro and in vivo experiments. Interaction of RBPs with non-coding RNAs was evaluated by RNA immune-precipitation and pull-down assay. RNA-seq whole genome sequencing and alternative splicing analysis were further performed to clarify post-transcription regulation mechanisms.
2023-10-24 | GSE245587 | GEO
Project description:To understand the global changes in genes expression after knockdown of LINC00152, we compared transcriptomes of control cells (treated with siGL2) and LINC00152 knockdown cells (treated with si00152).
2018-09-10 | GSE111652 | GEO
Project description:The long noncoding RNA LINC00152 shows ubiquitous expression and is often upregulated in tumor entities compared to healthy tissues. LINC00152 promotes malignant progression in the glioblastoma cell line U87. Here, LINC00152 knockdown leads to a reduction of migration and invasion of tumor cells. However, LINC00152 seems to have an opposite effect in another glioblastoma cell line A172. For this reason, the transcriptional patterns after LINC00152 knockdown in both cell lines (U87 and A172) were compared to identify the differences.
2021-01-01 | GSE161352 | GEO
Project description:Hepatocellular carcinoma (HCC) is notorious for its early and frequent metastases. To understand the molecular mechanisms underlying HCC metastasis, we generated a pulmonary metastasis HCC mouse model and performed both time-series transcriptomics and proteomics analysis of protein methylation. We found that methyltransferase NSD2 with significant upregulation in the tipping point for metastasis was closely correlated with high numbers of methylated-proteins in HCC tissues. NSD2 promoted the invasion and metastasis of HCC cells, both in vitro and in vivo. Mechanistically, NSD2 directly bound to PKM2, a glycolysis rate-limiting enzyme, and catalyzed di-methylation of PKM2 at the lysine 336 residue. Further investigation demonstrated that NSD2-mediated di-methylation of PKM2 increased the intracellular glycolytic rate and lactate production by enhancing its pyruvate kinase activity. High-lactate level in HCC cells lead to lactylation of splicing factor 3B subunit 1 (SF3B1) at lysine 333 residue, promoting SF3B1-mediated RNA splicing of several metastasis-related genes. Further, UNC8153, a novel NSD2-targeted degrader, inhibited HCC metastasis in PDX model. Altogether, our study identifies a key methyltransferase NSD2 for HCC metastasis and reveals a protein methylation-mediated molecular mechanism catalyzed by NSD2 integrate glycolysis regulation and alternative splicing.
2025-09-30 | PXD056645 | Pride
Project description:Hepatocellular carcinoma (HCC) is notorious for its early and frequent metastases. To understand the molecular mechanisms underlying HCC metastasis, we generated a pulmonary metastasis HCC mouse model and performed both time-series transcriptomics and proteomics analysis of protein methylation. We found that methyltransferase NSD2 with significant upregulation in the tipping point for metastasis was closely correlated with high numbers of methylated-proteins in HCC tissues. NSD2 promoted the invasion and metastasis of HCC cells, both in vitro and in vivo. Mechanistically, NSD2 directly bound to PKM2, a glycolysis rate-limiting enzyme, and catalyzed di-methylation of PKM2 at the lysine 336 residue. Further investigation demonstrated that NSD2-mediated di-methylation of PKM2 increased the intracellular glycolytic rate and lactate production by enhancing its pyruvate kinase activity. High-lactate level in HCC cells lead to lactylation of splicing factor 3B subunit 1 (SF3B1) at lysine 333 residue, promoting SF3B1-mediated RNA splicing of several metastasis-related genes. Further, UNC8153, a novel NSD2-targeted degrader, inhibited HCC metastasis in PDX model. Altogether, our study identifies a key methyltransferase NSD2 for HCC metastasis and reveals a protein methylation-mediated molecular mechanism catalyzed by NSD2 integrate glycolysis regulation and alternative splicing.
2025-09-30 | PXD056676 | Pride
Project description:Hepatocellular carcinoma (HCC) is notorious for its early and frequent metastases. To understand the molecular mechanisms underlying HCC metastasis, we generated a pulmonary metastasis HCC mouse model and performed both time-series transcriptomics and proteomics analysis of protein methylation. We found that methyltransferase NSD2 with significant upregulation in the tipping point for metastasis was closely correlated with high numbers of methylated-proteins in HCC tissues. NSD2 promoted the invasion and metastasis of HCC cells, both in vitro and in vivo. Mechanistically, NSD2 directly bound to PKM2, a glycolysis rate-limiting enzyme, and catalyzed di-methylation of PKM2 at the lysine 336 residue. Further investigation demonstrated that NSD2-mediated di-methylation of PKM2 increased the intracellular glycolytic rate and lactate production by enhancing its pyruvate kinase activity. High-lactate level in HCC cells lead to lactylation of splicing factor 3B subunit 1 (SF3B1) at lysine 333 residue, promoting SF3B1-mediated RNA splicing of several metastasis-related genes. Further, UNC8153, a novel NSD2-targeted degrader, inhibited HCC metastasis in PDX model. Altogether, our study identifies a key methyltransferase NSD2 for HCC metastasis and reveals a protein methylation-mediated molecular mechanism catalyzed by NSD2 integrate glycolysis regulation and alternative splicing.
2025-09-30 | PXD056672 | Pride
Project description:Hepatocellular carcinoma (HCC) is notorious for its early and frequent metastases. To understand the molecular mechanisms underlying HCC metastasis, we generated a pulmonary metastasis HCC mouse model and performed both time-series transcriptomics and proteomics analysis of protein methylation. We found that methyltransferase NSD2 with significant upregulation in the tipping point for metastasis was closely correlated with high numbers of methylated-proteins in HCC tissues. NSD2 promoted the invasion and metastasis of HCC cells, both in vitro and in vivo. Mechanistically, NSD2 directly bound to PKM2, a glycolysis rate-limiting enzyme, and catalyzed di-methylation of PKM2 at the lysine 336 residue. Further investigation demonstrated that NSD2-mediated di-methylation of PKM2 increased the intracellular glycolytic rate and lactate production by enhancing its pyruvate kinase activity. High-lactate level in HCC cells lead to lactylation of splicing factor 3B subunit 1 (SF3B1) at lysine 333 residue, promoting SF3B1-mediated RNA splicing of several metastasis-related genes. Further, UNC8153, a novel NSD2-targeted degrader, inhibited HCC metastasis in PDX model. Altogether, our study identifies a key methyltransferase NSD2 for HCC metastasis and reveals a protein methylation-mediated molecular mechanism catalyzed by NSD2 integrate glycolysis regulation and alternative splicing.
2025-09-30 | PXD056679 | Pride
Project description:Hepatocellular carcinoma (HCC) is notorious for its early and frequent metastases. To understand the molecular mechanisms underlying HCC metastasis, we generated a pulmonary metastasis HCC mouse model and performed both time-series transcriptomics and proteomics analysis of protein methylation. We found that methyltransferase NSD2 with significant upregulation in the tipping point for metastasis was closely correlated with high numbers of methylated-proteins in HCC tissues. NSD2 promoted the invasion and metastasis of HCC cells, both in vitro and in vivo. Mechanistically, NSD2 directly bound to PKM2, a glycolysis rate-limiting enzyme, and catalyzed di-methylation of PKM2 at the lysine 336 residue. Further investigation demonstrated that NSD2-mediated di-methylation of PKM2 increased the intracellular glycolytic rate and lactate production by enhancing its pyruvate kinase activity. High-lactate level in HCC cells lead to lactylation of splicing factor 3B subunit 1 (SF3B1) at lysine 333 residue, promoting SF3B1-mediated RNA splicing of several metastasis-related genes. Further, UNC8153, a novel NSD2-targeted degrader, inhibited HCC metastasis in PDX model. Altogether, our study identifies a key methyltransferase NSD2 for HCC metastasis and reveals a protein methylation-mediated molecular mechanism catalyzed by NSD2 integrate glycolysis regulation and alternative splicing.
2025-09-30 | PXD056688 | Pride
Project description:Hepatocellular carcinoma (HCC) is notorious for its early and frequent metastases. To understand the molecular mechanisms underlying HCC metastasis, we generated a pulmonary metastasis HCC mouse model and performed both time-series transcriptomics and proteomics analysis of protein methylation. We found that methyltransferase NSD2 with significant upregulation in the tipping point for metastasis was closely correlated with high numbers of methylated-proteins in HCC tissues. NSD2 promoted the invasion and metastasis of HCC cells, both in vitro and in vivo. Mechanistically, NSD2 directly bound to PKM2, a glycolysis rate-limiting enzyme, and catalyzed di-methylation of PKM2 at the lysine 336 residue. Further investigation demonstrated that NSD2-mediated di-methylation of PKM2 increased the intracellular glycolytic rate and lactate production by enhancing its pyruvate kinase activity. High-lactate level in HCC cells lead to lactylation of splicing factor 3B subunit 1 (SF3B1) at lysine 333 residue, promoting SF3B1-mediated RNA splicing of several metastasis-related genes. Further, UNC8153, a novel NSD2-targeted degrader, inhibited HCC metastasis in PDX model. Altogether, our study identifies a key methyltransferase NSD2 for HCC metastasis and reveals a protein methylation-mediated molecular mechanism catalyzed by NSD2 integrate glycolysis regulation and alternative splicing.
2025-09-29 | PXD056689 | Pride
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are using RNA sequencing analysis to evaluate the effects of si-LINC00152 on the mRNA of human colon cancer cell line HCT116. Methods: Human colon cancer cell line HCT116 was transfected with a control non-targeting siRNA to cells or transfected with siRNA targeting LINC00152 for 36 hours in DMEM medium (with 10% serum). Total RNA were extracted and detected by Illumina high-throughput RNA sequencing data analysis. 2 independent biological replicates were plated, transfected in parallel for each control and siRNA. Results: Log-fold changes of up- or down-regulated mRNAs between the control and experiment group were selected with a significance threshold of p<0.05. There are 90 mRNAs were up-regulated and 159 were down-regulated in “si-LINC00152” group comparing to “control” group. Conclusions: Our study describes the mRNA changes of human colon cancer cell line HCT116 transfected with LINC00152 siRNA.
2020-02-18 | GSE132519 | GEO