TWIST1-EP300 Expedites Gastric Cancer Cell Resistance to Apatinib by Activating the Expression of COL1A2

Yu, Gang; Chen, Wanjing; Li, Xianghua; Lan, Yu; Xu, Yanyan; Ruan, Qiang; He, Yawei; Wang, Yong

doi:10.1155/2022/5374262

Cited by 10 publications

(6 citation statements)

References 35 publications

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“…[ 41 ] COL1A2 was regulated by TWIST1-EP300 and LncRNA LIFR-AS1/miR-29a-3p axis thus contribute to apatinib resistance and GC progress. [ 42 , 43 ] COL1A2 also promoted BGC-823 and SGC-7901 apoptosis through the PI3k-Akt signaling pathway. [ 44 ] As for PDGFRB, it is showed that PDGFRB favored migration invasion and proliferation and CSC characteristics.…”

Section: Discussionmentioning

confidence: 99%

Identification of key genes associated with poor prognosis and neoplasm staging in gastric cancer

Wang,

Yang,

Liu

et al. 2023

Medicine

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Background: Gastric cancer (GC) is highly biologically and genetically heterogeneous disease with poor prognosis. Increasing evidence indicates that biomarkers can serve as prediction and clinical intervention. Therefore, it is vital to identify core molecules and pathways participating in the development of GC. Methods: In this study, GSE54129, GSE56807, GSE63089, and GSE118916 were used for identified overlapped 75 DEGs. GO and Kyoto Encyclopedia of Genes and Genomes pathway analysis showed DEGs mainly enriched in biological process about collagen-containing extracellular matrix and collagen metabolic. Next, protein-protein interaction network was built and the hub gene was excavated. Clinicopathological features and prognostic value were also evaluated. Results: Hub genes were shown as below, FN1, COL1A2, COL1A1, COL3A1, COL4A1, COL6A3, COL5A2, SPARC, PDGFRB, COL12A1. Those genes were upregulation in GC and related to the poor prognosis (except COL5A2, P = .73). What is more, high expression indicated worse T stage and tumor, node, metastasis stage in GC patients. Later, the results of 25 GC tumor specimens and 34 normal tissues showed that FN1, COL3A1, COL4A1, SPARC, COL5A2, and COL12A1 were significantly upregulated in cancer samples. Conclusion: Our study systematically explored the core genes and crucial pathways in GC, providing insights into clinical management and individual treatment.

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Section: Discussionmentioning

confidence: 99%

Identification of key genes associated with poor prognosis and neoplasm staging in gastric cancer

Wang,

Yang,

Liu

et al. 2023

Medicine

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“…Transcription factor enrichment analysis shows that they are mainly enriched in EP300, MAX, ESR1, ERG, BRD4, MYC, FOXA1, HIF1A, RUNX1, CTCF and other transcription factors. These transcription factors play an important role in the progression of gastric cancer, such as EP300 has the ability to regulate the expression of COL1A2 to control the drug resistance of gastric cancer cells to Apatinib (47). BRD4 activates C-MYC through transcriptional and epigenetic regulation, which increases the proliferation of gastric cancer cells and inhibits the apoptosis of gastric cancer cells(48).…”

Section: Discussionmentioning

confidence: 99%

Identification of memory B cell-associated miRNA signature to establish a prognostic model in gastric adenocarcinoma

Liu

Huang

Shao

et al. 2023

Preprint

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Background Memory B cells and microRNA (miRNA) play important roles in the progression of gastric adenocarcinoma (STAD). However, there are few studies on utility of memory B cell-associated miRNAs for prognosis of STAD. Methods We identified the marker genes of memory B cells by single-cell RNA sequencing (scRNA-seq) and identified the miRNAs associated with memory B cells by constructing an mRNA-miRNA co-expression network. Then, univariate Cox, random survival forest (RSF), and stepwise multiple Cox regression (StepCox) algorithms were used to identify memory B cell-associated miRNAs that were significantly related to overall survival (OS). A prognostic risk model was constructed and validated using these miRNAs, and patients were divided into a low-risk group and a high-risk group. In addition, the differences in clinicopathological features, tumour microenvironment, immune blocking therapy, and sensitivity of anticancer drugs in the two high versus low risk groups were analyzed. Results Four memory B cell-associated miRNAs (hsa-mir-145, hsa-mir-125b-2, hsa-mir-100, hsa-mir-221) with significantly correlation to OS were identified and used to construct a prognostic model. Time-dependent receiver operating characteristic (ROC) curve analysis confirmed the feasibility of the model. Kaplan-Meier (K-M) survival curve analysis showed that the prognosis was poor in the high-risk group. The comprehensive analysis showed that the patients in the high-risk group have higher immune scores, matrix scores, immune cell infiltration, and poor effect of immune response. In addition, in terms of drug screening, we predicted eight drugs with higher sensitivity in the high-risk group, of which CGP-60474 was the most sensitive. Conclusions In summary, we identified memory B cell-associated miRNAs prognostic features and constructed a novel risk model for STAD based on scRNA-seq data and bulk RNA-seq data. Patients in the high-risk group showed the highest sensitivity to GCP-60474. This study provides prognostic insights for individualized and accurate treatment of STAD patients.

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“…Transcription factor enrichment analysis showed that they were mainly enriched in EP300, MAX, ESR1, ERG, BRD4, MYC, FOXA1, HIF1A, RUNX1, CTCF and other transcription factors. These transcription factors play an important role in the progression of GC; for example, EP300 has the ability to regulate the expression of COL1A2 to control the drug resistance of gastric cancer cells to apatinib [47]. BRD4 activates C-MYC through transcriptional and epigenetic regulation, which increases the proliferation of gastric cancer cells and inhibits the apoptosis of gastric cancer cells [48].…”

Section: Discussionmentioning

confidence: 99%

Identification of memory B-cell-associated miRNA signature to establish a prognostic model in gastric adenocarcinoma

Liu,

Huang,

Shao

et al. 2023

J Transl Med

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Background Memory B cells and microRNAs (miRNAs) play important roles in the progression of gastric adenocarcinoma (GAC), also known as stomach adenocarcinoma (STAD). However, few studies have investigated the use of memory B-cell-associated miRNAs in predicting the prognosis of STAD. Methods We identified the marker genes of memory B cells by single-cell RNA sequencing (scRNA-seq) and identified the miRNAs associated with memory B cells by constructing an mRNA‒miRNA coexpression network. Then, univariate Cox, random survival forest (RSF), and stepwise multiple Cox regression (StepCox) algorithms were used to identify memory B-cell-associated miRNAs that were significantly related to overall survival (OS). A prognostic risk model was constructed and validated using these miRNAs, and patients were divided into a low-risk group and a high-risk group. In addition, the differences in clinicopathological features, tumour microenvironment, immune blocking therapy, and sensitivity to anticancer drugs in the two groups were analysed. Results Four memory B-cell-associated miRNAs (hsa-mir-145, hsa-mir-125b-2, hsa-mir-100, hsa-mir-221) with significant correlations to OS were identified and used to construct a prognostic model. Time-dependent receiver operating characteristic (ROC) curve analysis confirmed the feasibility of the model. Kaplan‒Meier (K‒M) survival curve analysis showed that the prognosis was poor in the high-risk group. Comprehensive analysis showed that patients in the high-risk group had higher immune scores, matrix scores, and immune cell infiltration and a poor immune response. In terms of drug screening, we predicted eight drugs with higher sensitivity in the high-risk group, of which CGP-60474 was associated with the greatest sensitivity. Conclusions In summary, we identified memory B-cell-associated miRNA prognostic features and constructed a novel risk model for STAD based on scRNA-seq data and bulk RNA-seq data. Among patients in the high-risk group, STAD showed the highest sensitivity to CGP-60474. This study provides prognostic insights into individualized and precise treatment for STAD patients.

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TWIST1-EP300 Expedites Gastric Cancer Cell Resistance to Apatinib by Activating the Expression of COL1A2

Cited by 10 publications

References 35 publications

Identification of key genes associated with poor prognosis and neoplasm staging in gastric cancer

Identification of key genes associated with poor prognosis and neoplasm staging in gastric cancer

Identification of memory B cell-associated miRNA signature to establish a prognostic model in gastric adenocarcinoma

Identification of memory B-cell-associated miRNA signature to establish a prognostic model in gastric adenocarcinoma

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