Moesin facilitates metastasis of hepatocellular carcinoma cells by improving invadopodia formation and activating β-catenin/MMP9 axis

Lan, Shubing; Zheng, Xiaoyuan; Hu, Ping; Xing, Xiaohua; Ke, Kun; Wang, Fei; Cheng, Niangmei; Zhuang, Qiuyu; Liu, Xiaolong; Liu, Jingfeng; Zhao, Bixing; Wang, Yingchao

doi:10.1016/j.bbrc.2020.01.157

Cited by 17 publications

(14 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Meanwhile, angiogenesis and the expression of in ammatory factors in surrounding tissues induced by ectopic exosomes might also be correlated with the overexpression of MMP9. There is a study on the correlation between MSN and MMP9 showed that, in individual tumors, the expression of MSN and MMP9 remains consistent, which jointly promotes tumor metastasis [43]. In our study, ectopic exosomal MSN up-regulated the expression of MMP9 in target cells and induced an increase in the secretion of VEGF, thereby promoting angiogenesis.…”

Section: Discussionsupporting

confidence: 65%

Exosomal Moesin Derives From Ectopic Stromal Cells Constructs A “Migration-Vascularization-Inflammation” Loop In Endometriosis

Abudula

Fan

Zhang

et al. 2021

Preprint

View full text Add to dashboard Cite

Background: Endometriosis (EMS) is the most common gynaecological disorder with its etiology and/or pathophysiology remains enigmatic. Recent studies showed that extracellular vesicles (EVs), exosomes namely, play a critical role in the development of various clinical disorders, including inflammatory disease and cancers. Previous studies revealed the role of exosomes as a potential biomarker in EMS. However, the implication of exosomes in the disease progression of EMS has not been well elucidated. Method: The biological function of ectopic exosomes (eEVs) was examined by Transwell assay, scratch tests, tube formation assay, western blot, and qRT-PCR analysis. Mass spectrometry analysis of the exosomes isolated from fresh EMS tissue and vaginal discharge obtained from patients with and without EMS used to identify differentially expressed protein in exosomes from ectopic stromal cells (ESCs) and normal endometrial stromal cells (NESCs). Gene knockdown was used to downregulate the expression of exosomal protein in in-vivo setting. Finally, in-vitro experiment confirmed the results that we observed in endometriosis (EMS) mouse model. Results: We found that eEVs increased the migration ability of NESCs) by up-regulating MMP9 expression. We also observed that eEVs facilitate angiogenesis, and induced the high expression of inflammatory cytokines in ovarian epithelial cells. Protein Mass spectrometry and bioinformatics analysis showed that Moesin (MSN) is highly expressed in eEVs. An abnormal high estrogen environment may up-regulate MSN expression in ectopic lesion. Downregulation of exosomal Moesin attenuated the migration capability of normal endometrium, inhibited angiogenesis, and reduced the expression of inflammatory cytokine. Moreover, we found that ectopic exosomes significantly increased the number and size of heterotopic foci in vivo. Also, we observed an increase in the size of vascular lumen, and upregulation of inflammatory factors expression in small intestine adjacent to the heterotopic foci. Conclusion: Exosomal MSN from ectopic stromal cells could contribute to the development of EMS by mediating the construction of a “migration-vascularization-inflammation” loop in ectopic environment.

show abstract

Section: Discussionsupporting

confidence: 65%

Exosomal Moesin Derives From Ectopic Stromal Cells Constructs A “Migration-Vascularization-Inflammation” Loop In Endometriosis

Abudula

Fan

Zhang

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Besides the DE mRNAs enriched in GO terms and KEGG pathways, several top DE mRNAs function in the regulation of cell proliferation. Matrix metallopeptidase 9 (MMP9) has been shown to be involved in promoting proliferation ( Lan et al, 2020 ). Human concentrative nucleoside transporter-1 (hCNT1, SLC28A1) ( Wang and Buolamwini, 2019 ), Ccl20 ( Qiu et al, 2011 ), Sema4d ( Bhutia et al, 2011 ), and Arhgap36 ( Rack et al, 2014 ) have been shown to influence cellular growth and proliferation, and were the top down-regulated mRNAs in V79 cells cultured in a DUGL.…”

Section: Discussionmentioning

confidence: 99%

Whole Transcriptome Analysis Revealed a Stress Response to Deep Underground Environment Conditions in Chinese Hamster V79 Lung Fibroblast Cells

et al. 2021

View full text Add to dashboard Cite

Background: Prior studies have shown that the proliferation of V79 lung fibroblast cells could be inhibited by low background radiation (LBR) in deep underground laboratory (DUGL). In the current study, we revealed further molecular changes by performing whole transcriptome analysis on the expression profiles of long non-coding RNA (lncRNA), messenger RNA (mRNA), circular RNA (circRNA) and microRNA (miRNA) in V79 cells cultured for two days in a DUGL.Methods: Whole transcriptome analysis including lncRNA, mRNAs, circ RNA and miRNA was performed in V79 cells cultured for two days in DUGL and above ground laboratory (AGL), respectively. The differentially expressed (DE) lncRNA, mRNA, circRNA, and miRNA in V79 cells were identified by the comparison between DUGL and AGL groups. Quantitative real-time polymerase chain reaction(qRT-PCR)was conducted to verify the selected RNA sequencings. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway was analyzed for the DE mRNAs which enabled to predict target genes of lncRNA and host genes of circRNA.Results: With |log2(Fold-change)| ≥ 1.0 and p < 0.05, a total of 1257 mRNAs (353 mRNAs up-regulated, 904 mRNAs down-regulated), 866 lncRNAs (145 lncRNAs up-regulated, 721 lncRNAs down-regulated), and 474 circRNAs (247 circRNAs up-regulated, 227 circRNAs down-regulated) were significantly altered between the two groups. There was no significant difference in miRNA between the two groups. The altered RNA profiles were mainly discovered in lncRNAs, mRNAs and circRNAs. DE RNAs were involved in many pathways including ECM-RI, PI3K-Akt signaling, RNA transport and the cell cycle under the LBR stress of the deep underground environment.Conclusion: Taken together, these results suggest that the LBR in the DUGL could induce transcriptional repression, thus reducing metabolic process and reprogramming the overall gene expression profile in V79 cells.

show abstract

“…[ 38 – 41 ] Wu et al [ 42 ] revealed that ECM1 interacts with MSN and facilitates invadopodia formation, which is required for stromal invasion and metastasis in breast cancer. Similarly, in hepatocellular carcinoma cells, Lan et al [ 43 ] identified that moesin promotes metastasis by improving invadopodia formation and activating the β-catenin/MMP9 axis. However, the potential role of MSN in EC remained unknown.…”

Section: Discussionmentioning

confidence: 99%

Identification of MTHFD2 as a novel prognosis biomarker in esophageal carcinoma patients based on transcriptomic data and methylation profiling

et al. 2020

View full text Add to dashboard Cite

DNA methylation is an important epigenetic regulatory mechanism in esophageal carcinoma (EC) and is associated with genomic instability and carcinogenesis. In the present study, we aimed to identify tumor biomarkers for predicting prognosis of EC patients. We downloaded mRNA expression profiles and DNA methylation profiles associated with EC from the Gene Expression Omnibus database. Differentially expressed and differentially methylated genes between tumor tissues and adjacent normal tissue samples were identified. Functional enrichment analyses were performed, followed by the construction of protein–protein interaction networks. Data were validated based on methylation profiles from The Cancer Genome Atlas. Candidate genes were further verified according to survival analysis and Cox regression analysis. We uncovered multiple genes with differential expression or methylation in tumor samples compared with normal samples. After taking the intersection of 3 differential gene sets, we obtained a total of 232 overlapping genes. Functional enrichment analysis revealed that these genes are related to pathways such as “glutathione metabolism,” “p53 signaling pathway,” and “focal adhesion.” Furthermore, 8 hub genes with inversed expression and methylation correlation were identified as candidate genes. The abnormal expression levels of MSN, PELI1, and MTHFD2 were correlated with overall survival times in EC patients ( P < .05). Only MTHFD2 was significantly associated with a pathologic stage according to univariate analysis ( P = .037) and multivariate analysis ( P = .043). Our study identified several novel EC biomarkers with prognostic value by integrated analysis of transcriptomic data and methylation profiles. MTHFD2 could serve as an independent biomarker for predicting prognosis and pathological stages of EC.

show abstract

Moesin facilitates metastasis of hepatocellular carcinoma cells by improving invadopodia formation and activating β-catenin/MMP9 axis

Cited by 17 publications

References 19 publications

Exosomal Moesin Derives From Ectopic Stromal Cells Constructs A “Migration-Vascularization-Inflammation” Loop In Endometriosis

Exosomal Moesin Derives From Ectopic Stromal Cells Constructs A “Migration-Vascularization-Inflammation” Loop In Endometriosis

Whole Transcriptome Analysis Revealed a Stress Response to Deep Underground Environment Conditions in Chinese Hamster V79 Lung Fibroblast Cells

Identification of MTHFD2 as a novel prognosis biomarker in esophageal carcinoma patients based on transcriptomic data and methylation profiling

Contact Info

Product

Resources

About