Tumor-derived exosomes orchestrate the microRNA-128-3p/ELF4/CDX2 axis to facilitate the growth and metastasis of gastric cancer via delivery of LINC01091

Wang, Qiang; Zhang, Chunmei; Cao, Shengya; Zhao, Hongying; Jiang, Rongke; Li, Yanfang

doi:10.1007/s10565-022-09728-y

Cited by 13 publications

(8 citation statements)

References 34 publications

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“…Studies have reported that Hippo-YAP signaling is important for the activation of nuclear transcription factor CDX2 expression in mouse embryos [ 30 , 31 ]. Meanwhile, CDX2 is preferentially expressed in GC [ 32 , 33 ]. Therefore, we further explored the relationship between YAP and CDX2 in GC.…”

Section: Resultsmentioning

confidence: 99%

“…Notably, downregulation of YAP results in a decline of CDX2 expression in GC cells [ 43 ]. CDX2 is abundant in GC tissues and cells, which augments the proliferative, migrating, and invasive properties of GC cells [ 32 ]. Altogether, these lines of evidence suggest a novel regulatory pathway of H19/YAP/CDX2 in GC which can serve as a potential target for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

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LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network

et al. 2023

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Background Extracellular vesicles (EVs) transport biologically active molecules, and represent a recently identified way of intercellular communication. Recent evidence has also reported that EVs shed by cancer stem cells (CSCs) make a significant contribution to carcinogenesis and metastasis. Here, this study aims to explore the possible molecular mechanism of CSCs-EVs in gastric cancer (GC) by mediating intratumor communication network. Methods CSCs and non-stem cancer cells (NSCCs) were sorted from GC cells, and EVs were isolated from CSCs. H19 was knocked down in CSCs, and CSCs-EVs or CSCs-EVs containing shRNA-H19 (CSCs-EVs-sh-H19) were co-cultured with NSCCs, followed by evaluation of the malignant behaviors and stemness of NSCCs. Mouse models of GC were established and injected with CSCs-EVs from sh-H19-treated NSCCs in vivo. Results CSCs had notable self-renewal and tumorigenic capacity compared with NSCCs. CSCs promoted the malignant behaviors of NSCCs and expression of stemness marker proteins through secretion of EVs. Inhibited secretion of CSCs-EVs curtailed the tumorigenicity and metastasis of NSCCs in vivo. H19 could be delivered by CSCs-EVs into NSCCs. H19 promoted the malignant behaviors of NSCCs and stemness marker protein expression in vitro along with tumorigenicity and liver metastasis in vivo, which was mechanistically associated with activation of the YAP/CDX2 signaling axis. Conclusion Taken together, the present study points to the importance of a novel regulatory axis H19/YAP/CDX2 in carcinogenic and metastatic potential of CSCs-EVs in GC, which may be potential targets for anticancer therapy.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network

et al. 2023

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“…LINC01091 and LINC01359 were also found to be deregulated in the three main subtypes of male infertility, namely asthenozoospermia [ 41 ], teratozoospermia [ 45 ], and oligozoospermia [ 37 ]. LINC01091 also seems to have a role in cancer, as it regulates tumorigenesis and metastasis in gastric cancer [ 99 ], and is also implicated to have a role in prostate cancer [ 100 ]. Similarly, it has been reported that LINC01359 could serve as a potential biomarker for hepatocellular carcinoma [ 101 ].…”

Section: Discussionmentioning

confidence: 99%

The Role of Long Noncoding RNAs on Male Infertility: A Systematic Review and In Silico Analysis

Kyrgiafini

Sarafidou

Mamuris

2022

Biology

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Male infertility is a complex disorder affecting many couples worldwide. Long noncoding RNAs (lncRNAs) regulate important cellular processes; however, a comprehensive understanding of their role in male infertility is limited. This systematic review investigates the differential expressions of lncRNAs in male infertility or variations in lncRNA regions associated with it. The PRISMA guidelines were used to search Pubmed and Web of Science (1 June 2022). Inclusion criteria were human participants, patients diagnosed with male infertility, and English language speakers. We also performed an in silico analysis investigating lncRNAs that are reported in many subtypes of male infertility. A total of 625 articles were found, and after the screening and eligibility stages, 20 studies were included in the final sample. Many lncRNAs are deregulated in male infertility, and interactions between lncRNAs and miRNAs play an important role. However, there is a knowledge gap regarding the impact of variants found in lncRNA regions. Furthermore, eight lncRNAs were identified as differentially expressed in many subtypes of male infertility. After in silico analysis, gene ontology (GO) and KEGG enrichment analysis of the genes targeted by them revealed their association with bladder and prostate cancer. However, pathways involved in general in tumorigenesis and cancer development of all types, such as p53 pathways, apoptosis, and cell death, were also enriched, indicating a link between cancer and male infertility. This evidence, however, is preliminary. Future research is needed to explore the exact mechanism of action of the identified lncRNAs and investigate the association between male infertility and cancer.

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“…For instance, ELF4 is highly expressed in human glioblastomas (GBM), promotes GBM cell proliferation and stemness, and influences the survival periods of GBM patients [9]. In gastric cancer, ELF4 is upregulated by LINC01091, which then transcriptionally upregulates the expression of CDX2 to promote the development of GC [10]. In HBV-associated HCC, ELF4 activates telomerase to drive the progression of HCC, and the sphere-forming property of HCC cells is suppressed after ELF4 knockdown [11].…”

Section: Ivyspringmentioning

confidence: 99%

FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC

Chen¹,

Chen²,

Feng³

et al. 2023

Theranostics

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Background: Metastasis accounts for the high lethality of colorectal cancer (CRC) patients. Unfortunately, the molecular mechanism manipulating metastasis in CRC is still elusive. Here, we investigated the function of E74-like factor 4 (ELF4), an ETS family member, in facilitating CRC progression. Methods: The expression of ELF4 in human CRC samples and CRC cell lines was determined by quantitative real-time PCR, immunohistochemistry and immunoblotting. The migratory and invasive phenotypes of CRC cells were evaluated by in vitro transwell assays and in vivo metastatic models. The RNA sequencing was used to explore the downstream targets of ELF4. The luciferase reporter assays and chromatin immunoprecipitation assays were used to ascertain the transcriptional regulation related to ELF4. Results: We found elevated ELF4 was positively correlated with distant metastasis, advanced AJCC stages, and dismal outcomes in CRC patients. ELF4 expression was also an independent predictor of poor prognosis. Overexpression of ELF4 boosted CRC metastasis via transactivating its downstream target genes, fibroblast growth factor receptor 4 (FGFR4) and SRC proto-oncogene, non-receptor tyrosine kinase, SRC. Fibroblast growth factor 19 (FGF19) upregulated ELF4 expression through the ERK1/2/SP1 axis. Clinically, ELF4 expression had a positive correlation with FGF19, FGFR4 and SRC, and CRC patients who positively coexpressed FGF19/ELF4, ELF4/FGFR4, or ELF4/SRC exhibited the worst clinical outcomes. Furthermore, the combination of the FGFR4 inhibitor BLU-554 and the SRC inhibitor KX2-391 dramatically suppressed ELF4-mediated CRC metastasis. Conclusions: We demonstrated the essentiality of ELF4 in the metastatic process of CRC, and targeting the ELF4-relevant positive feedback circuit might represent a novel therapeutic strategy.

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Tumor-derived exosomes orchestrate the microRNA-128-3p/ELF4/CDX2 axis to facilitate the growth and metastasis of gastric cancer via delivery of LINC01091

Cited by 13 publications

References 34 publications

LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network

LncRNA H19-rich extracellular vesicles derived from gastric cancer stem cells facilitate tumorigenicity and metastasis via mediating intratumor communication network

The Role of Long Noncoding RNAs on Male Infertility: A Systematic Review and In Silico Analysis

FGF19-mediated ELF4 overexpression promotes colorectal cancer metastasis through transactivating FGFR4 and SRC

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