Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation

Sugimachi, Keizō; Matsumura, Tae; Hirata, Hidenari; Uchi, Ryutaro; Ueda, Masami; Ueo, Hiroaki; Shinden, Yoshiaki; Iguchi, Tomohiro; Eguchi, Hidetoshi; Shirabe, Ken; Ochiya, Takahiro; Maehara, Yoshihiko; Mimori, Koshi

doi:10.1038/bjc.2014.621

Cited by 269 publications

(188 citation statements)

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“…Plasma (1.0 ml) was used for microarray analysis, and 500 µl was used for RT-qPCR. The exosomes of the plasma were purified by the ultracentrifugation method, as described previously (21). In brief, the exosomes were separated by ultracentrifugation at 100,000 x g for 70 min at 4˚C, and then the pellets were washed with phosphate-buffered saline (PBS) and stored at -80˚C for microarray and RT-qPCR analysis.…”

Section: Purification Of Exosomes From Plasmamentioning

confidence: 99%

“…cDNA was synthesized from total RNA using Taqman microRNA primers specific for hsa-miR-21 (assay ID 000397), has-miR-4257 (assay ID 244369) and has-miR-16a (assay ID 000391) (Thermo Fisher Scientific, Inc., Waltham, MA, USA) and a TaqMan Micro-RNA Reverse Transcription kit (Thermo Fisher Scientific, Inc.). miR-16a was used as an internal control, as it is reported to be a reliable endogenous control for miRNA analysis in RT-qPCR for humans (21). RT-qPCR was performed using Lightcycler-480 (Roche Applied Science, Basel, Switzerland) and Taqman Universal PCR Master Mix (Thermo Fisher Scientific, Inc.) following the manufacturer's protocols.…”

Section: Purification Of Exosomes From Plasmamentioning

confidence: 99%

“…To evaluate the correlation between the exosomal miR-21 and miR-4257 expression levels and the clinicopathological characteristics, patients were divided into two groups (high and low). The cut-off level was determined as the average of the miR-21 and miR-4257 expression levels, as described previously (21). As shown in Table III, a statistically significant association was observed between the high miR-21 group and tumor size and TNM stage.…”

Section: Expression Of Exosomal Mir-21 and Mir-4257mentioning

confidence: 99%

“…However, the existing biomarkers, such as cancer-associated antigens, and proteomics analysis are unsatisfactory for the early stages of NSCLC. By contrast, recent studies have demonstrated that specific expression profiles of circulating exosomal miRNAs could be promising biomarkers for the detection of early-stage cancer and for predicting prognosis in various types of cancers (19)(20)(21). However, previous studies in NSCLC have not examined exosomal miRNAs, which could be expected to include the intact miRNA.…”

Section: Introductionmentioning

confidence: 99%

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Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

et al. 2017

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Abstract. Predictive biomarkers for the recurrence of non-small cell lung cancer (NSCLC) in patients who have received curative resection are important for cancer treatment. The functional microRNAs (miRNAs/miRs) in the exosomes of plasma and serum samples are of interest as stable and non-invasive biomarkers for recurrence in cancer patients. The aim of the present study was to clarify the usefulness of plasma exosomal miRNAs as biomarkers for the prediction of recurrence in NSCLC following curative resection. First, microarray-based expression profiling of miRNAs derived from exosomes in the plasma of 6 patients was employed to identify a biomarker that distinguishes between patients with and without NSCLC recurrence. In the miRNA microarray analyses, the exosomal miR-21 and miR-4257 levels of the NSCLC patients showed marked upregulation in those individuals with recurrence compared with those without recurrence and healthy individuals. These two miRNAs were thus selected as recurrence-specific biomarkers and their potential was evaluated in a separate cohort of 195 NSCLC patients. In comparison to the levels in 30 healthy individuals, exosomal miR-21 and miR-4257 levels showed a significant increase in the NSCLC patients (P<0.01). When evaluating the clinicopathological significance of these miRNAs, exosomal miR-21 showed a significant association with tumor size and tumor-node-metastasis (TNM) stage (P<0.05). Exosomal miR-4257 showed a significant association with histological type, lymphatic invasion and TNM stage (P<0.05). The disease-free survival (DFS) rates of high exosomal miR-21 patients were significantly worse than those of low exosomal miR-21 patients (P<0.05), and the DFS rates of patients with high exosomal miR-4257 levels were significantly worse than those with low exosomal miR-4257 levels (P<0.01). In the Cox multivariate analysis, plasma exosomal miR-21 and miR-4257 expression showed a significance association with DFS (P<0.05). These results suggest that plasma exosomal miR-21 and mir-4257 expression has potential as a predictive biomarker for recurrence in NSCLC patients who have received curative resection. IntroductionLung cancer, mainly non-small cell lung cancer (NSCLC), is the leading cause of cancer-associated mortality globally. More than 133,000 new diagnoses and over 77,000 associated mortalities are expected to occur in 2015 in Japan (1). In spite of progress in NSCLC therapy, the prognosis for patients with NSCLC remains poor (2). Therefore, clarification of the biomarkers most likely to predict the recurrence of NSCLC after curative surgery is required to improve the outcome of NSCLC patients.MicroRNAs (miRNAs/miRs) are one of the most compelling molecular markers in the diagnosis and prognosis of tumors (3,4). miRNAs are short (20-24 nt) non-coding RNAs that take part in the post-transcriptional regulation of gene expression in multicellular organisms by impacting mRNA stability and translation. miRNAs target protein-coding mRNAs at the post-transcriptional level by directly c...

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Section: Purification Of Exosomes From Plasmamentioning

confidence: 99%

Section: Purification Of Exosomes From Plasmamentioning

confidence: 99%

Section: Expression Of Exosomal Mir-21 and Mir-4257mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

et al. 2017

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“…The onset and progress of HCC are not evident, and thus most HCC cases are diagnosed at an advanced stage, which may mean that they are not then suitable for surgical resection. Additionally, the drugs for advanced HCC are limited and ineffective, which contributes to the poor prognosis (Bronte et al, 2015;Sugimachi et al, 2015). Thus, novel strategies for the early diagnosis and therapy of HCC need to be developed.…”

Section: Introductionmentioning

confidence: 99%

Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells

Wang¹,

Chen

et al. 2017

J. Zhejiang Univ. Sci. B

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Abstract:Objective: Hepatocellular carcinoma (HCC) is still one of the most common death-related malignancies worldwide. Because the way onset and progression are hidden most, HCC diagnoses are made at an advanced stage, when they are unsuitable for surgical resection. MicroRNAs are a class of small non-coding RNAs, participating in many aspects of cancers. In this study, we tried to establish the role of microRNA-718 (miR-718) in the malignant phenotype of HCC cells and its possible role in HCC diagnosis. Methods: Here we first used a methylthiazolyldiphenyltetrazolium bromide (MTT) assay, Transwell migration and invasion assays, and colony formation assay to evaluate the impact of miR-718 on the malignant phenotypes of HCC cells. Then, we used bioinformatic methods to predict the target gene of miR-718 and used green fluorescence protein (GFP) reporter assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR) to validate the regulation relationship. Finally, we determined the role of the target gene in the HCC phenotype. Results: We found that the expression of miR-718 was significantly reduced in various HCC cell lines and HCC tissues. Re-expression of miR-718 significantly reduced the cellular viability and colony formation ability as well as inhibited the migration and invasion abilities of HCC cell lines. Early growth response protein 3 (EGR3) is a direct target of miR-718 and is negatively regulated by miR-718. EGR3 could increase the viability and proliferation of HCC cells, and promot the migration and invasion of HCC cells. Conclusions: miR-718 acts as a tumor suppressive microRNA in HCC via regulating the expression of EGR3, which may provide a new diagnostic marker and treatment target for HCC.

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Extracellular Vesicles and Exosomes

Szabó

Momen-Heravi

2020

The Liver

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Identification of a bona fide microRNA biomarker in serum exosomes that predicts hepatocellular carcinoma recurrence after liver transplantation

Cited by 269 publications

References 38 publications

Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

Exosomal microRNA in plasma as a non-invasive biomarker for the recurrence of non-small cell lung cancer

Involvement of microRNA-718, a new regulator of EGR3, in regulation of malignant phenotype of HCC cells

Extracellular Vesicles and Exosomes

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