Exosome‑encapsulated microRNA‑23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage

Kumata, Yoshimasa; Iinuma, Hisae; Suzuki, Yusuke; Tsukahara, Daisuke; Midorikawa, Hironori; Igarashi, Yuichi; Soeda, Naruyoshi; Kiyokawa, Takashi; Horikawa, Masahiro

doi:10.3892/or.2018.6418

Cited by 49 publications

(44 citation statements)

References 31 publications

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“…Considering that exosomes are highly stable disease biomarkers, exo-miRNAs may be potential GC diagnostic or prognostic biomarkers that are more accurate and stable than miRNAs [26][27][28]. In order to explore whether exo-miR-15b-3p performs the above functions, we first extracted and purified exosomes from the conditioned media of three cell lines (BGC-823, SGC-7901 and GES-1) and the serum of GC patients and non-GC volunteers (n = 108, patients and volunteers as listed in Table 1).…”

Section: Serum Exo-mir-15b-3p As a Potential Gc Diagnosis And Prognosmentioning

confidence: 99%

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

Wei

Peng

Yang

et al. 2020

J Exp Clin Cancer Res

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Background: Exosomes are essential for tumor growth, metastasis, and are used as novel signaling molecules in targeted therapies. Therefore, exosomal miRNAs can be used in new diagnostic and therapeutic approaches due to their involvement in the development of cancers. However, the detailed biological function, potential molecular mechanism and clinical application of exo-miR-15b-3p in gastric cancer (GC) remains unclear.Methods: miR-15b-3p mRNA levels in tissues, serum, cells and exosomes were analyzed using qRT-PCR assays. qRT-PCR, immunohistochemical and western blotting analyses were utilized for the determination of DYNLT1 expression. The interrelationship connecting miR-15b-3p with DYNLT1 was verified using Dual-luciferase report, western blotting and qRT-PCR assays. Fluorescent PKH-26 or GFP-Lv-CD63 labeled exosomes, as well as Cy3-miR-15b-3p, were utilized to determine the efficacy of the transfer of exo-miR-15b-3p between BGC-823 and recipient cells. Several in vitro assays and xenograft tumor models were conducted to determine exo-miR-15b-3p impact on GC progression.Results: This is the first study to confirm high miR-15b-3p expression in GC cell lines, tissues and serum. Exosomes obtained from 108 GC patient serum samples and GC cell-conditioned medium were found to show upregulation of exo-miR-15b-3p, with the area under the ROC curve (AUC) being 0.820 [0.763-0.876], which is superior to the AUC of tissues and serum miR-15b-3p (0.674 [0.600-0.748] and 0.642 [0.499-0.786], respectively). In addition, high exo-miR-15b-3p expression in serum was found to accurately predict worse overall survival. SGC-7901 and GES-1 cells are capable of internalizing BGC-823 cell-derived exosomes, allowing the transfer of miR-15b-3p. Migration, invasion, proliferation and inhibition of apoptosis in vitro and in vivo were enhanced by exo-miR-15b-3p, by restraining DYNLT1, Cleaved Caspase-9 and Caspase-3 expression.Conclusions: This study identified a previously unknown regulatory pathway, exo-miR-15b-3p/DYNLT1/Caspase-3/ Caspase-9, which promotes GC development and GES-1 cell malignant transformation. Therefore, serum exo-miR-15b-3p may be a potential GC diagnosis and prognosis biomarker, which can be used in precise targeted GC therapy.

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Section: Serum Exo-mir-15b-3p As a Potential Gc Diagnosis And Prognosmentioning

confidence: 99%

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

Wei

Peng

Yang

et al. 2020

J Exp Clin Cancer Res

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“…Several reports have highlighted the clinical significance of circulating exosomal RNAs, especially miRNAs, for GC diagnosis. [7][8][9] However, the low quantity and specificity of circulating miRNAs greatly limits their value as diagnostic molecules, and other types of RNAs, such as long non-coding RNAs (lncRNAs), may be more suitable as diagnostic markers. However, the significance of cancer cell-derived exosomal lncRNA in plasma or serum for GC diagnosis remains unclear.…”

Section: Introductionmentioning

confidence: 99%

<p>Exosomal Long Non-Coding RNA CEBPA-AS1 Inhibits Tumor Apoptosis and Functions as a Non-Invasive Biomarker for Diagnosis of Gastric Cancer</p>

Piao¹,

Guo²,

Wang³

et al. 2020

OTT

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Traditional non-invasive diagnostic markers for gastric cancer (GC) exhibit insufficient sensitivity and specificity. Circulating exosomes are clinically useful non-invasive biomarkers for tumor diagnosis. In addition to their potential role in cancer biology, circulating long non-coding RNAs (lncRNAs) are a new class of promising cancer biomarkers. In the present study, we aimed to identify lncRNAs in circulating exosomes with potential as biomarkers for GC detection. Methods: We compared the expression of CEBPA-AS1 between GC cells and gastric epithelial cells. The biological function of exosomal CEBPA-AS1 was determined by cell phenotype experiments and rescue assays. We also compared the expression of CEBPA-AS1 in cancerous tissue from GC patients and corresponding adjacent normal tissues, as well as the expression of CEBPA-AS1 in plasma exosomes of GC patients and healthy controls. Diagnostic accuracy was assessed by the receiver operating characteristic (ROC) curve and area under the curve (AUC). Results: CEBPA-AS1 was highly expressed in both GC cells and in exosomes secreted by GC cells. In addition, CEBPA-AS1-containing exosomes secreted by GC cells could promote cell proliferation and inhibit apoptosis, thereby inducing the malignant behavior of GC cells. The level of CEBPA-AS1 was also significantly increased in tissues and plasma exosomes of GC patients. Stability tests showed that most plasma CEBPA-AS1 was encased in exosomes, thus avoiding degradation by RNases. We evaluated the diagnostic accuracy of exosomederived CEBPA-AS1. The AUC value of CEBPA-AS1 in discriminating GC patients from healthy controls was 0.824, which was higher than the diagnostic accuracy of other traditional tumor biomarkers. Conclusion: CEBPA-AS1-containing exosomes secreted from GC cells could promote cell proliferation, inhibit apoptosis, and induce GC progression, indicating that exosomal CEBPA-AS1 is involved in cell-to-cell communication in GC carcinogenesis. Exosomal CEBPA-AS1 is a promising new biomarker for clinical diagnosis of GC.

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“…Exosomes are nano-sized membrane vesicles with diameters between 30 and 100 nm (21)(22)(23). It has previously been reported that cancer-associated exosomes serve important roles in regulating the cellular functions of cancerous cells, fibroblasts, vascular smooth muscle cells and endothelial cells through effectively delivering microRNAs, mRNAs and proteins (24)(25)(26)(27)(28)(29). However, the functions of exosomes in GBM progression and radiotherapy remain unknown.…”

Section: Introductionmentioning

confidence: 99%

AHIF promotes glioblastoma progression and radioresistance via exosomes

et al. 2018

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Glioblastoma multiforme (GBM) has the highest mortality rate among patients with brain tumors, and radiotherapy forms an important part of its treatment. Thus, there is an urgent requirement to elucidate the mechanisms conferring GBM progression and radioresistance. In the present study, it was identified that antisense transcript of hypoxia-inducible factor-1α (AHIF) was significantly upregulated in GBM cancerous tissues, as well as in radioresistant GBM cells. The expression of AHIF was also upregulated in response to radiation. Knockdown of AHIF in GBM cells decreased viability and invasive capacities, and increased the proportion of apoptotic cells. By contrast, overexpression of AHIF in GBM cells increased viability and invasive capacities, and decreased the proportion of apoptotic cells. Furthermore, exosomes derived from AHIF-knockdown GBM cells inhibited viability, invasion and radioresistance, whereas exosomes derived from AHIF-overexpressing GBM cells promoted viability, invasion and radioresistance. Further biochemical analysis identified that AHIF regulates factors associated with migration and angiogenesis in exosomes. To the best of our knowledge, the present study is the first to establish that AHIF promotes glioblastoma progression and radioresistance via exosomes, which suggests that AHIF is a potential therapeutic target for GBM.

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Exosome‑encapsulated microRNA‑23b as a minimally invasive liquid biomarker for the prediction of recurrence and prognosis of gastric cancer patients in each tumor stage

Cited by 49 publications

References 31 publications

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

Exosomal transfer of miR-15b-3p enhances tumorigenesis and malignant transformation through the DYNLT1/Caspase-3/Caspase-9 signaling pathway in gastric cancer

<p>Exosomal Long Non-Coding RNA CEBPA-AS1 Inhibits Tumor Apoptosis and Functions as a Non-Invasive Biomarker for Diagnosis of Gastric Cancer</p>

AHIF promotes glioblastoma progression and radioresistance via exosomes

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