Identification of combinatorial miRNA panels derived from extracellular vesicles as biomarkers for esophageal squamous cell carcinoma

Wang, Yaojie; Li, Xiaoya; Wei, Xiaojian; Li, Lei; Bai, Hanyu; Yan, Xi; Zhang, Hongtao; Zhao, Libo; Zhou, Wei; Zhao, Lianmei

doi:10.1002/mco2.377

Cited by 3 publications

(2 citation statements)

References 50 publications

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“…Then, miRNA microarray revealed that miR‐1246 was not only one of the top 10 miRNAs in EVs of 143B, but also the most upregulated miRNA compared with MNNG cells. Notably, miR‐1246 could promote different tumor metastasis such as lung cancer, 16 esophageal squamous cell carcinoma, 17 and oral squamous cell carcinoma. 18 Thus, we chose EVs‐derived miR‐1246 as an example of the potent NamiRNAs to clarify how NamiRNAs modulate osteosarcoma metastasis and explore the roles of AGO2 during this process.…”

Section: Introductionmentioning

confidence: 99%

miR‐1246 promotes osteosarcoma cell migration via NamiRNA‐enhancer network dependent on Argonaute 2

Yang,

Zou,

Liang

et al. 2024

MedComm

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High metastatic propensity of osteosarcoma leads to its therapeutic failure and poor prognosis. Although nuclear activation miRNAs (NamiRNAs) are reported to activate gene transcription via targeting enhancer and further promote tumor metastasis, it remains uncertain whether NamiRNAs regulate osteosarcoma metastasis and their exact mechanism. Here, we found that extracellular vesicles of the malignant osteosarcoma cells (143B) remarkably increased the migratory abilities of MNNG cells representing the benign osteosarcoma cells by two folds, which attributed to their high miR‐1246 levels. Specially, miR‐1246 located in nucleus could activate the migration gene expression (such as MMP1) to accelerate MNNG cell migration through elevating the enhancer activities via increasing H3K27ac enrichment. Instead, MMP1 expression was dramatically inhibited after Argonaute 2 (AGO2) knockdown. Notably, in vitro assays demonstrated that AGO2 recognized the hybrids of miR‐1246 and its enhancer DNA via PAZ domains to prevent their degradation from RNase H and these protective roles of AGO2 may favor the gene activation by miR‐1246 in vivo. Collectively, our findings suggest that miR‐1246 could facilitate osteosarcoma metastasis through interacting with enhancer to activate gene expression dependent on AGO2, highlighting the nuclear AGO2 as a guardian for NamiRNA‐targeted gene activation and the potential of miR‐1246 for osteosarcoma metastasis therapy.

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Section: Introductionmentioning

confidence: 99%

miR‐1246 promotes osteosarcoma cell migration via NamiRNA‐enhancer network dependent on Argonaute 2

Yang,

Zou,

Liang

et al. 2024

MedComm

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“…Although miRs as diagnostic markers for cancers still have unresolved problems, they can show good potential in clinical application according to different cancer types and sample sources [16]. In study related to esophageal squamous cell carcinoma, miRs can be potential therapeutic targets as well as potential prognostic indicators [17]. The use of miR-525 in cancer diagnosis and treatment has rarely been investigated in studies.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic and prognostic role of microRNA-525 in different cancers: A systematic review and meta-analysis

ZHAO,

PAN,

GAO

et al. 2024

Preprint

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Background New prospect of cancer therapeutical management seems to be early diagnosis and prognosis prediction by microRNAs. The aim of our study is to explore the role of miR-525 in cancer diagnosis and prognosis through a systematic review and meta-analysis. Methods We conducted systematic search through PubMed, Embase, Web of Science, Scopus, Medline, Chinese National Knowledge Infrastructure (CNKI) and Wanfang databases up to November 25, 2023, regardless of language restrictions. Sensitivity, specificity, and diagnostic odds ratio (DOR) were extracted for diagnostic meta-analysis, while hazard ratio (HR) with 95% confidence interval (CI) for prognostic meta-analysis. Subgroup analysis and publication bias analysis were performed appropriately to investigate possible sources of heterogeneity. Results A total of 8 studies were included in the meta-analysis, of which 7 were used for diagnostic meta-analysis, covering 559 patients, and 3 were used for prognostic meta-analysis, covering 324 patients. The pooled sensitivity was 0.75 (95%CI = 0.70 to 0.79), specificity was 0.73 (95%CI = 0.68 to 0.78), DOR was 13.08 (95%CI = 4.18 ~ 40.91), and the area under the curve ratio (AUC) was 0.86 (95%CI = 0.83–0.89). Subgroup analysis showed that miR-525 may have good diagnostic ability in the early TNM stage of cancer. Prognostic meta-analysis showed that low miR-525 expression in patients was associated with preferable survival (HR = 0.17, 95%CI = 0.07–0.9). Conclusions Our findings suggest that miR-525 could be used as a potential biomarker for cancer patients. Low expression of miR-525 in cancers predicted a good prognosis.

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Targeted delivery of extracellular vesicles: the mechanisms, techniques and therapeutic applications

Zhao,

Di,

Fan

et al. 2024

Mol Biomed

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Extracellular vesicles (EVs) are cell-derived vesicles with a phospholipid bilayer measuring 50–150 nm in diameter with demonstrated therapeutic potentials. Limitations such as the natural biodistribution (mainly concentrated in the liver and spleen) and short plasma half-life of EVs present significant challenges to their clinical translation. In recent years, growing research indicated that engineered EVs with enhanced targeting to lesion sites have markedly promoted therapeutic efficacy. However, there is a dearth of systematic knowledge on the recent advances in engineering EVs for targeted delivery. Herein, we provide an overview of the targeting mechanisms, engineering techniques, and clinical translations of natural and engineered EVs in therapeutic applications. Enrichment of EVs at lesion sites may be achieved through the recognition of tissue markers, pathological changes, and the circumvention of mononuclear phagocyte system (MPS). Alternatively, external stimuli, including magnetic fields and ultrasound, may also be employed. EV engineering techniques that fulfill targeting functions includes genetic engineering, membrane fusion, chemical modification and physical modification. A comparative statistical analysis was conducted to elucidate the discrepancies between the diverse techniques on size, morphology, stability, targeting and therapeutic efficacy in vitro and in vivo. Additionally, a summary of the registered clinical trials utilizing EVs from 2010 to 2023 has been provided, with a full discussion on the perspectives. This review provides a comprehensive overview of the mechanisms and techniques associated with targeted delivery of EVs in therapeutic applications to advocate further explorations of engineered EVs and accelerate their clinical applications.

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Identification of combinatorial miRNA panels derived from extracellular vesicles as biomarkers for esophageal squamous cell carcinoma

Cited by 3 publications

References 50 publications

miR‐1246 promotes osteosarcoma cell migration via NamiRNA‐enhancer network dependent on Argonaute 2

miR‐1246 promotes osteosarcoma cell migration via NamiRNA‐enhancer network dependent on Argonaute 2

Diagnostic and prognostic role of microRNA-525 in different cancers: A systematic review and meta-analysis

Targeted delivery of extracellular vesicles: the mechanisms, techniques and therapeutic applications

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