RETRACTED ARTICLE: M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade

Zhang, Yu; Meng, Wenbo; Yue, Ping; Li, Xun

doi:10.1186/s13046-020-01626-7

Cited by 47 publications

(38 citation statements)

References 38 publications

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“…Overall, our analysis indicates that mRNAsi values positively correlate with PD-L1 expression and negatively correlate with macrophages and CAFs. We know that macrophages, especially M2 macrophages ( 27 ), and CAFs ( 28 , 29 ) play important roles in driving the progression of GC. By evaluating the numbers of these two types of cells, the outcome of GC can be better predicted.…”

Section: Resultsmentioning

confidence: 99%

Identification of Stemness Characteristics Associated With the Immune Microenvironment and Prognosis in Gastric Cancer

et al. 2021

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BackgroundGastric cancer (GC) is a highly heterogeneous disease. In recent years, the prognostic value of the mRNA expression-based stemness index (mRNAsi) across cancers has been reported. We intended to identify stemness index-associated genes (SI-genes) for clinical characteristic, gene mutation status, immune response, and tumor microenvironment evaluation as well as risk stratification and survival prediction.MethodsThe correlations between the mRNAsi and GC prognosis, clinical characteristics, gene mutation status, immune cell infiltration and tumor microenvironment were evaluated. Weighted gene correlation network analysis (WGCNA) was performed to identify SI-genes from differentially expressed genes (DEGs) in The Cancer Genome Atlas (TCGA). Single-sample gene set enrichment analysis (ssGSEA) was employed to calculate the sample SI-gene-based ssGSEA score according to the SI-genes. Then, the correlations between the ssGSEA score and GC prognosis, clinical characteristics, gene mutation status, immune cell infiltration and tumor microenvironment were analyzed. Finally, the least absolute shrinkage and selection operator (LASSO) Cox regression algorithm was used to construct a prognostic signature with prognostic SI-genes. The ssGSEA score and prognostic signature were validated using the Gene Expression Omnibus (GEO) database.ResultsThe mRNAsi could predict overall survival (OS), clinical characteristics, the gene mutation status, immune cell infiltration, and the tumor microenvironment composition. Fourteen positive SI-genes and 178 negative SI-genes were screened out using WGCNA. The ssGSEA score, similar to the mRNAsi, was found to be closely related to OS, clinical characteristics, the gene mutation status, immune cell infiltration, and the tumor microenvironment composition. Finally, a prognostic signature based on 18 prognostic SI-genes was verified to more accurately predict GC 1-year, 3-year, and 5-year OS than traditional clinical prediction models.ConclusionThe ssGSEA score and prognostic signature based on 18 prognostic SI-genes are of great value for immune response evaluation, risk stratification and survival prediction in GC and suggest that stemness features are crucial drivers of GC progression.

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Section: Resultsmentioning

confidence: 99%

Identification of Stemness Characteristics Associated With the Immune Microenvironment and Prognosis in Gastric Cancer

et al. 2021

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“… 31 revealed that miR-130b-3p upregulation promoted cell proliferation, invasion, and migration but diminished cell apoptosis in bladder cancer by targeting PTEN. Furthermore, another research group 32 also uncovered that miR-130b-3p overexpression transferred by M2 macrophage-derived EVs accelerated the proliferation, migration, and invasion of gastric cancer cells.…”

Section: Discussionmentioning

confidence: 97%

microRNA-130b-3p contained in MSC-derived EVs promotes lung cancer progression by regulating the FOXO3/NFE2L2/TXNRD1 axis

Guo

Yan

Song

et al. 2021

Molecular Therapy - Oncolytics

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This study aimed to explore the molecular mechanism by which mesenchymal stem cells (MSCs) mediate lung cancer progression. Extracellular vesicles (EVs) were isolated from transfected or untransfected MSCs, and were co-cultured with lung cancer cells with/without microRNA-130b-3p (miR-130b-3p) inhibitor, mimic, overexpression plasmids of FOXO3/NFE2L2, or shRNAs. CCK-8 assay, colony formation, transwell assay, and flow cytometry were carried out to determine the biological functioning of lung cancer cells. Furthermore, FOXO3, Keap1, NFE2L2, and TXNRD1 expression was determined by qRT-PCR and western blot analysis. A tumor xenograft mouse model was used to determine role of EVs-miR-130b-3p and its target FOXO3 in lung cancer progression in vivo . miR-130b-3p was highly expressed in lung cancer tissues and MSC-derived EVs. Moreover, the MSC-derived EVs transferred miR-130b-3p to lung cancer cells to promote cell proliferation, migration, and invasion while repress cell apoptosis. miR-130b-3p directly targeted FOXO3, and FOXO3 elevated Keap1 expression to downregulate NFE2L2, thus inhibiting TXNRD1. FOXO3 overexpression or silencing of NFE2L2 or TXNRD1 diminished lung cancer cell proliferation, invasion, and migration but enhanced apoptosis. EV-delivered miR-130b-3p or FOXO3 silencing promoted lung cancer progression in vivo . In summary, MSC-derived EVs with upregulated miR-130b-3p suppressed FOXO3 to block the NFE2L2/TXNRD1 pathway, thus playing an oncogenic role in lung cancer progression.

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“…Zhang et al. found miR-130b delivered in M2 macrophage-derived extracellular vesicles promoted survival, migration, invasion, and angiogenesis of GC cells ( 37 ). A recent study showed that plasma miR-130b expression were associated with response to 5-FU/oxaliplatin treatment in metastatic colorectal cancer (mCRC) and upregulated in non-responders ( 38 ).…”

Section: Discussionmentioning

confidence: 99%

“…Lai et al reported that overexpression of miR-130b increased cell viability, reduced cell death and decreased expression of Bim via regulating of tumor suppressor RUNX3 (36). Zhang et al found miR-130b delivered in M2 macrophage-derived extracellular vesicles promoted survival, migration, invasion, and angiogenesis of GC cells (37). A recent study showed that plasma miR-130b expression were associated with response to 5-FU/oxaliplatin treatment in metastatic colorectal cancer (mCRC) and upregulated in non-responders (38).…”

Section: Discussionmentioning

confidence: 99%

CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer

Chu

Han

2021

Front. Oncol.

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Gastric cancer (GC) remains a major world-wide challenge, especially in Asian countries. Chemotherapy with 5-fluorouracil (5-FU) and cisplatin is used as the first-line treatment and development of chemoresistance is a major cause of progression. UMP/CMP kinase is responsible for the phosphorylation of the ribonucleotide metabolite 5-fluoro-5′-monophosphate (FUMP) in 5-FU metabolic process, and recognized as a key step in the conversion of 5-FU to cytotoxic metabolites. Our bioinformatics analysis and molecular experiments demonstrated that high expression of CMPK1 was associated with prolonged survival and response to 5-FU treatment in GC samples. Further analysis demonstrated that miR-130b as a key epigenetic regulator of CMPK1, and miR-130b-mediated attenuation of CMPK1 resulted in resistance of gastric cancer cells to DNA damage and cell death after treatment with 5-FU. Rescue experiments with augmented CMPK1 expression abolished the effect of miR-130b demonstrating the key function of this miRNA in this pathway. Thus, this newly identified miR-130b-CMPK1 axis suggests a potentially new chemotherapeutic strategy for improved response to 5-FU therapy.

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RETRACTED ARTICLE: M2 macrophage-derived extracellular vesicles promote gastric cancer progression via a microRNA-130b-3p/MLL3/GRHL2 signaling cascade

Cited by 47 publications

References 38 publications

Identification of Stemness Characteristics Associated With the Immune Microenvironment and Prognosis in Gastric Cancer

Identification of Stemness Characteristics Associated With the Immune Microenvironment and Prognosis in Gastric Cancer

microRNA-130b-3p contained in MSC-derived EVs promotes lung cancer progression by regulating the FOXO3/NFE2L2/TXNRD1 axis

CMPK1 Regulated by miR-130b Attenuates Response to 5-FU Treatment in Gastric Cancer

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