Exosomal miR-628-5p from M1 polarized macrophages hinders m6A modification of circFUT8 to suppress hepatocellular carcinoma progression

Wang, Liyan; Yi, Xiaoyuan; Xiao, Xuejun; Zheng, Qianqian; Ma, Lei; Li, Bin

doi:10.1186/s11658-022-00406-9

Cited by 47 publications

(27 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As the most abundant RNA modification, m6A modification displays vital and different biological functions in multiple tumor progression [ 26 , 35 – 37 ]. Although studies revealed that the m6A methyltransferase exhibits oncogenic activity in DLBCL [ 20 , 38 ], there is little direct evidence showing other modulators as oncogenic or tumor suppressive effects.…”

Section: Discussionmentioning

confidence: 99%

KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo–YAP pathway

et al. 2023

View full text Add to dashboard Cite

Background N6-methyladenosine (m6A) has been shown to participate in various essential biological processes by regulating the level of target genes. However, the function of m6A modification mediated by KIAA1429 [alias virus-like m6A methyltransferase-associated protein (VIRMA)] during the progression of diffuse large B-cell lymphoma (DLBCL) remains undefined. Methods The expression and clinical significance of KIAA1429 were verified by our clinical data. CRISPR/Cas9 mediated KIAA1429 deletion, and CRISPR/dCas9-VP64 for activating endogenous KIAA1429 was used to evaluate its biological function. RNA sequencing (RNA-seq), methylated RNA immunoprecipitation sequencing (MeRIP-seq), RNA immunoprecipitation (RIP) assays, luciferase activity assay, RNA stability experiments, and co-immunoprecipitation were performed to investigate the regulatory mechanism of KIAA1429 in DLBCL. Tumor xenograft models were established for in vivo experiments. Results Dysregulated expression of m6A regulators was observed, and a novel predictive model based on m6A score was established in DLBCL. Additionally, elevated KIAA1429 expression was associated with poor prognosis of patients with DLBCL. Knockout of KIAA1429 repressed DLBCL cell proliferation, facilitated cell cycle arrest in the G2/M phase, induced apoptosis in vitro, and inhibited tumor growth in vivo. Furthermore, carbohydrate sulfotransferase 11 (CHST11) was identified as a downstream target of KIAA1429, which mediated m6A modification of CHST11 mRNA and then recruited YTHDF2 for reducing CHST11 stability and expression. Inhibition of CHST11 diminished MOB1B expression, resulting in inactivation of Hippo–YAP signaling, reprogramming the expression of Hippo target genes. Conclusions Our results revealed a new mechanism by which the Hippo–YAP pathway in DLBCL is inactivated by KIAA1429/YTHDF2-coupled epitranscriptional repression of CHST11, highlighting the potential of KIAA1429 as a novel predictive biomarker and therapeutic target for DLBCL progression.

show abstract

Section: Discussionmentioning

confidence: 99%

KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo–YAP pathway

et al. 2023

View full text Add to dashboard Cite

show abstract

“…Therapeutic targeting of UCK2 and its downregulation may lead to an increase in cancer immunity in HCC [ 28 ]. Since molecular interactions play a key role in HCC progression [ 29 , 30 ], the current review was dedicated to understanding the function of STAT3 signaling in HCC tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

et al. 2023

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) is considered one of the greatest challenges to human life and is the most common form of liver cancer. Treatment of HCC depends on chemotherapy, radiotherapy, surgery, and immunotherapy, all of which have their own drawbacks, and patients may develop resistance to these therapies due to the aggressive behavior of HCC cells. New and effective therapies for HCC can be developed by targeting molecular signaling pathways. The expression of signal transducer and activator of transcription 3 (STAT3) in human cancer cells changes, and during cancer progression, the expression tends to increase. After induction of STAT3 signaling by growth factors and cytokines, STAT3 is phosphorylated and translocated to the nucleus to regulate cancer progression. The concept of the current review revolves around the expression and phosphorylation status of STAT3 in HCC, and studies show that the expression of STAT3 is high during the progression of HCC. This review addresses the function of STAT3 as an oncogenic factor in HCC, as STAT3 is able to prevent apoptosis and thus promote the progression of HCC. Moreover, STAT3 regulates both survival- and death-inducing autophagy in HCC and promotes cancer metastasis by inducing the epithelial–mesenchymal transition (EMT). In addition, upregulation of STAT3 is associated with the occurrence of chemoresistance and radioresistance in HCC. Specifically, non-protein-coding transcripts regulate STAT3 signaling in HCC, and their inhibition by antitumor agents may affect tumor progression. In this review, all these topics are discussed in detail to provide further insight into the role of STAT3 in tumorigenesis, treatment resistance, and pharmacological regulation of HCC. Graphical Abstract

show abstract

“…Macrophage exosomal miRNAs have also been reported to affect tumorigenesis. For instance, M1 macrophage-derived exosomal miR-628-5p inhibits the development of hepatocellular carcinoma [ 15 ], whereas M2 macrophage-derived exosomal miR-3917 promotes the progression of lung cancer [ 16 ]. M2 macrophage-derived exosomal miR-21-5p, miR-155-5p, miR-221-5p, and miR-501-3p promote the differentiation and activity of PC stem cells [ 17 ] and the growth, angiogenesis [ 18 ], migration, and invasion of PC cells [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

M2 macrophage-derived exosomal miR-193b-3p promotes progression and glutamine uptake of pancreatic cancer by targeting TRIM62

Zhang

Peng

et al. 2023

Biol Direct

View full text Add to dashboard Cite

Background Pancreatic cancer (PC) is a highly lethal malignancy that requires effective novel therapies. M2 macrophages are abundant in the PC microenvironment and promote cancer progression. Exosomes are emerging mediators of the crosstalk between cancer cells and the microenvironment. This study was conducted to explore the role of M2 macrophage-derived exosomes in PC. Methods Exosomes derived from M2 macrophages were extracted. miR-193b-3p and TRIM62 were overexpressed or silenced to examine their function in PC. Luminescence assays were used to investigate the interaction between miR-193b-3p and TRIM62. Cell proliferation was examined by EdU staining. Would healing and transwell assays were applied to evaluate cell migration and invasion. Co-immunoprecipitation was used to assess the interaction between TRIM62 and c-Myc. Gene and protein expressions were analyzed by quantitative RT-PCR and immunoblotting, respectively. Results M2 macrophage-derived exosomal miR-193b-3p promoted the proliferation, migration, invasion, and glutamine uptake of SW1990 cells. Mechanism study revealed that TRIM62 is a target of miR-193b-3p. TRIM62 inhibited the proliferation, migration, invasion, and glutamine uptake of SW1990 cells by promoting c-Myc ubiquitination. Our data also suggested that TRIM62 expression negatively correlated with miR-193b-3p and c-Myc expression. High-expression of miR-193b-3p and c-Myc predicts poor prognosis, whereas low-expression of TRIM62 predicts poor prognosis in patients with PC. Conclusion M2 macrophage-derived exosomal miR-193b-3p enhances the proliferation, migration, invasion, and glutamine uptake of PC cells by targeting TRIM62, resulting in the decrease of c-Myc ubiquitination. This study not only reveals the mechanism underlying the crosstalk between M2 macrophages and PC cells but also suggests a promising therapeutic target for PC.

show abstract

Exosomal miR-628-5p from M1 polarized macrophages hinders m6A modification of circFUT8 to suppress hepatocellular carcinoma progression

Cited by 47 publications

References 32 publications

KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo–YAP pathway

KIAA1429-mediated m6A modification of CHST11 promotes progression of diffuse large B-cell lymphoma by regulating Hippo–YAP pathway

Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance

M2 macrophage-derived exosomal miR-193b-3p promotes progression and glutamine uptake of pancreatic cancer by targeting TRIM62

Contact Info

Product

Resources

About