IRF4 overexpression promotes the transdifferentiation of tregs into macrophage‐like cells to inhibit the development of colon cancer

Wang, Jiwei; Song, Li; Li, Honglang; Zhou, Xiaoshuang; Wen, Hao; Lai, Bin

doi:10.1186/s12935-021-01766-6

Cited by 13 publications

(9 citation statements)

References 32 publications

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“…We can find that there are many immune-related molecules. IRF4 overexpression promotes the transdifferentiation of Tregs into macrophage-like cells ( Wang et al, 2021 ). In hepatocellular carcinoma, CD48/2B4 interactions could mediate the dysfunction of monocyte/macrophage-elicited natural killer cell ( Wu et al, 2013 ).…”

Section: Resultsmentioning

confidence: 99%

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis

Liu

Shen

et al. 2022

Front. Genet.

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Ovarian cancer (OC) is the most lethal gynecological malignancy, in which chemoresistance is a crucial factor leading to the poor prognosis. Recently, immunotherapy has brought new light for the treatment of solid tumors. Hence, as a kind of immunologically active cancer, it is reasonably necessary to explore the potential mechanism between immune characteristics and cisplatin resistance in OC. Our study focused on the important role of cisplatin resistance-related lncRNAs on mediating the OC tumor immune microenvironment (TIME) using an integrative analysis based on the Cancer Genome Atlas (TCGA) database. First, the cisplatin resistance-related differentially expressed lncRNAs (DELs) and mRNAs (DEMs) were preliminarily screened to construct a DEL–DEM co-expression network. Next, the protein–protein interaction (PPI) network and pivot analysis were performed to reveal the relevance of these lncRNAs with tumor immune response. Second, the novel lncRNA CTD-2288O8.1 was identified as a key gene for the OC cisplatin resistance formation by qRT-PCR and survival analysis. Gain- and loss-of-function assays (Cell Counting Kit-8 (CCK-8) assay, wound-healing scratch assay, transwell assay, and colony formation assay) further verified the activity of CTD-2288O8.1 in OC progression as well. Third, gene set enrichment analysis (GSEA) was applied along with the correlation analyses of CTD-2288O8.1 with ImmuneScore, tumor-infiltrating immune cells (TICs), and immune inhibitory checkpoint molecules, illustrating that CTD-2288O8.1 was strongly associated with the TIME and has the potential to predict the effect of OC immunotherapy. In addition, basic experiments demonstrated that the expression of CTD-2288O8.1 impacted the EGFR/AKT signal pathway activity of OC tumor cells. Of greater significance, it promoted the M2 polarization of macrophage, which is a type of the most important components of the TIME in solid tumor. Taking together, our study revealed cisplatin resistance-related lncRNAs closely linked with tumor immunity in OC, underscoring the potential mechanism of the TIME in conferring cisplatin resistance, which provided the research basis for further clinical treatment. CTD-2288O8.1 was identified to mediate cisplatin resistance and affect the response of immunotherapy, which could serve as a promising biomarker for guiding clinical treatment and improving prognosis in OC.

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Section: Resultsmentioning

confidence: 99%

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis

Liu

Shen

et al. 2022

Front. Genet.

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“…Fortunately, transcriptome sequencing showed that in addition to increasing the expression of PGC-1α, DHM could also enhance IRF4 expression. IRF4 is a transcription factor that is known for its function in regulating the immune system and oncogenesis [ 41 ]. Moreover, IRF4 participates in almost all metabolic activities of WAT, including inhibiting insulin-induced lipogenesis by downregulating the expression of genes related to adipogenesis, promoting lipolysis by upregulating the expression of adipocyte triglyceride lipase and hormone-sensitive lipase [ 22 ] and improving inflammation by promoting adipose tissue M2 macrophage polarization [ 42 ].…”

Section: Discussionmentioning

confidence: 99%

Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α

Leng

Zhou

et al. 2022

Nutr Metab (Lond)

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Background Promoting the browning of white adipose tissue (WAT) is a promising approach for the treatment of obesity and related comorbidities because it increases energy expenditure. In this study, we investigated whether Dihydromyricetin (DHM), a flavonoid component, could ameliorate diet-induced obesity through promoting the browning of WAT. Methods Male C57BL/6 J mice were received a high-fat diet (HFD) to induce obesity and subsequently were treated with DHM (100 mg/kg/day) or vehicle for 4 weeks. The effects of DHM on weight reduction and metabolic phenotype improvement were observed in the mice. The expression of genes and protein involved in browning of WAT were assessed in inguinal WAT (iWAT) of the mice. Then, the effect of DHM on the inducing browning program was verified in adipocytes differentiated from stromal vascular fraction (SVF) cells of mouse iWAT. Finally, the mechanism by which DHM improves the browning of WAT was explored using RNA-seq and luciferase reporter assay. Results We find that DHM reduces body weight, decreases WAT mass, improves glucose and lipid metabolic disorders, and ameliorates hepatic steatosis in diet-induced obese (DIO) mice. Further studies show that DHM induces WAT browning, which is manifested by increased expression of uncoupling protein 1 (UCP1) and peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α and enhanced mitochondrial activity in iWAT and primary adipocytes. In addition, we also find that DHM enhances interferon regulatory factor 4 (IRF4) expression, which is a key transcriptional regulator of PGC-1α. Conclusion Our findings identify that DHM prevents obesity by inducing the browning of WAT through the upregulation of IRF4/PGC-1α, which may have potential therapeutic implications for the treatment of obesity.

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“…In terms of colon cancer, there is a significant correlation between miR-320c levels in plasma exosomes and nerve invasion [ 53 ]. Wang et al found that exosomes of colon cancer cells promoted the progression of colon cancer by inhibiting the expression level of interferon regulatory factor 4 (IRF4) in regulatory T cells (Tregs) by transferring miR-320c [ 54 ]. Overall, there is a paucity of studies on miR-320c and further in vitro and in vivo studies are needed to confirm its association with colon cancer.…”

Section: Discussionmentioning

confidence: 99%

Construction of a miRNA-mRNA Network Related to Exosomes in Colon Cancer

Dong

et al. 2022

Disease Markers

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Background. The competing endogenous RNA (CeRNA) network plays important roles in the occurrence and development of colon cancer. This research is aimed at constructing a miRNA-mRNA network associated with exosomes in colon cancer. Methods. We explored the GEO database and then analyzed the RNAs of 722 samples to obtain differentially expressed miRNAs (DEMs) and mRNAs (DEGs) alongside the progress of colon cancer. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of DEM target genes and DEGs were performed. In addition, a miRNA-mRNA network related to exosomes in colon cancer was constructed based on DEMs and DEGs. Finally, the expression of miRNA and mRNA in the network was verified by GEPIA2 on the base of TCGA database. Results. Through our analysis, 19 DEMs (17 up and 2 down) and 1672 DEGs (954 up and 718 down) were screened. The GO and KEGG results show that these DEGs were mainly enriched in ribonucleoprotein complex biogenesis, noncoding RNA metabolic process, cell-substrate junction, cadherin binding, transcription coregulator activity, and regulation of the human T-cell leukemia virus 1 infection-related pathway. Besides, a miRNA-mRNA network, including 4 miRNAs (hsa-miR-623, hsa-miR-320c, hsa-miR-486-5p, and hsa-miR-1290) and 7 mRNAs (GNAI1, CADM1, PGRMC2, etc.), was constructed. Three of these seven mRNAs were downregulated in colon cancer. Ultimately, the GNAI1, CADM1, and PGRMC2 expression levels were verified by TCGA database. Conclusions. This study reveals the network relationship between colon cancer exosome-derived miRNA and targeted mRNA. It deepens our understanding of new molecular mechanisms and pathways that may play a role in the occurrence and metastasis of colon cancer.

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IRF4 overexpression promotes the transdifferentiation of tregs into macrophage‐like cells to inhibit the development of colon cancer

Cited by 13 publications

References 32 publications

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis

Identification of a Novel Immune-Related lncRNA CTD-2288O8.1 Regulating Cisplatin Resistance in Ovarian Cancer Based on Integrated Analysis

Dihydromyricetin ameliorates diet-induced obesity and promotes browning of white adipose tissue by upregulating IRF4/PGC-1α

Construction of a miRNA-mRNA Network Related to Exosomes in Colon Cancer

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