Serum Exosomal MicroRNA, miR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular Carcinoma

Cho, Hyo Jung; Eun, Jung Woo; Baek, Geum Ok; Seo, Chul Won; Ahn, Hye Shin; Kim, Soon Sun; Cho, Sung Won; Cheong, Jae Youn

doi:10.3390/jcm9010281

Cited by 94 publications

(66 citation statements)

References 27 publications

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“…Mir‐10b is a tumor‐associated miRNA in many types of cancer. It could be enriched in exosomes of hepatocellular carcinoma cells and was a potential marker for the diagnosis of early‐stage hepatocellular carcinoma 14 . Hypoxia could induce the expression of miR‐10b‐3p and promote the growth and metastasis of esophageal squamous cell carcinoma by targeting TSGA10 15 .…”

Section: Discussionmentioning

confidence: 99%

MiR‐10b inhibits migration and invasion of pancreatic ductal adenocarcinoma via regulating E2F7

Cui

2020

Clinical Laboratory Analysis

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Background Abnormal microRNAs (miRNAs) expression is closely related to the development and poor prognosis of pancreatic ductal adenocarcinoma (PDAC). We aimed to elucidate the invasive mechanism and clinical significance of miR‐10b in PDAC. Methods The RNA sequence data of pancreatic cancer were extracted from the TCGA database. R packages were performed to analyze the differential expression of RNAs. TargetScan, picTar, and miRanda were used to predict the target gene of miRNA. The expression level of the selected candidate was tested by western blot and RT‐PCR in PDAC cells and tissues. Scrape and Transwell assays were determined the effect of candidate molecules on cell migration and invasion. The gain of function and loss of function was achieved by co‐culture with mimics and vector. Luciferase reporters were generated based on the psiCHECK2 vector. The relative luciferase activity was measured with the Dual‐Luciferase Reporter Assay System and Infinate M200 PRO microplate reader. Results Based on the TCGA data and bioinformatics analysis, we obtained seven differentially expressed miRNAs. Both TCGA data and our center clinical date indicated that miR‐10b was contributed to the poor survival of PDAC. Based on the target gene prediction database, we found that E2F7 was a target mRNA of miR‐10b. In subsequent experiments in molecular biology, miR‐10b expression was downregulated in PDAC cells and tissues, while E2F7 was upregulated. Scrape and Transwell assay indicated that miR‐10b could inhibit the invasion and migration of PDAC. MiR‐10b was confirmed to be by the E2F7 targeting site by dual‐luciferase report. Moreover, rescue experiments prove that miR‐10b could inhibit the invasion and migration of PDAC cells by regulating E2F7 expression. Conclusion Our results suggest that miR‐10b could inhibit the progression of PDAC by regulating E2F7 expression and acts as an independent prognostic risk factor for PDAC.

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Section: Discussionmentioning

confidence: 99%

MiR‐10b inhibits migration and invasion of pancreatic ductal adenocarcinoma via regulating E2F7

Cui

2020

Clinical Laboratory Analysis

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“…Following this study, many other investigations identified several miRNAs in exosomes as diagnostic (Table 2) or prognostic (Table 3) biomarkers in HCC. [132] miR-744 ↓ 68 HCC and 52 normal liver tissue samples Proliferation and chemoresistance [114] CHB: chronic hepatitis B; CLD: chronic liver disease; HCC: hepatocellular carcinoma; LC: liver cirrhosis.…”

Section: Exosomal Mirnas As Potential Biomarkers In Hccmentioning

confidence: 99%

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

Pascut

Pratama

Võ

et al. 2020

Cancers

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The communication between hepatocellular carcinoma (HCC) cells and their microenvironment is an essential mechanism supporting or preventing tumor development and progression. Recent evidence has identified extracellular vesicles (EVs) as one of the mechanisms mediating paracrine signaling between cells. Exosomes, the most described class of EVs, deliver proteins, mRNAs, noncoding RNAs, DNA, and lipids to recipient cells, also at remote distances. MicroRNAs (miRNAs), as part of the non-coding RNA exosomal cargo, have an important role in regulating cellular pathways in targeted cells, regulating several processes related to tumor progression invasion and metastasis, such as angiogenesis, immune-escape, epithelial-to-mesenchymal transition, invasion, and multi-drug resistance. Accumulating evidence suggests exosomal miRNAs as relevant players in the dynamic crosstalk among cancerous, immune, and stromal cells in establishing the tumorigenic microenvironment. In addition, they sustain the metastasic niche formation at distant sites. In this review, we summarized the recent findings on the role of the exosome-derived miRNAs in the cross-communication between tumor cells and different hepatic resident cells, with a focus on the molecular mechanisms responsible for the cell re-programming. In addition, we describe the clinical implication derived from the exosomal miRNA-driven immunomodulation to the current immunotherapy strategies and the molecular aspects influencing the resistance to therapeutic agents.

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“…High protein and RNA expression was observed on the surface of EVs in the majority of studies involving HCC cases. The most thoroughly investigated marker was miRNAs associated with small EVs [ 82 , 83 , 84 , 85 ]. Data on the ability of miRNAs to distinguish HCC from healthy individuals showed that exosomal miR-122, miR-148a, miR-1246 [ 82 ], miR-10b-5p, miR-18a-5p, miR-215-5p and miR-940 [ 83 ] may be used in clinical practice.…”

Section: Evs In Gastrointestinal (Gi) and Liver Cancer Managementmentioning

confidence: 99%

“…Two points need to be stressed here. First, the high degrees of sensitivity and specificity of these miRNAs, especially miR-122 [ 82 ] and miR-10b-5p [ 83 ], for HCC diagnosis were confirmed. Second, the measurement of exosomal miR-215-5p in blood might give additional information on patients’ prognosis [ 83 ].…”

Section: Evs In Gastrointestinal (Gi) and Liver Cancer Managementmentioning

confidence: 99%

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

Słomka

Mocan

Wang

et al. 2020

Cancers

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For more than a decade, extracellular vesicles (EVs) have been in focus of science. Once thought to be an efficient way to eliminate undesirable cell content, EVs are now well-accepted as being an important alternative to cytokines and chemokines in cell-to-cell communication route. With their cargos, mainly consisting of functional proteins, lipids and nucleic acids, they can activate signalling cascades and thus change the phenotype of recipient cells at local and systemic levels. Their substantial role as modulators of various physiological and pathological processes is acknowledged. Importantly, more and more evidence arises that EVs play a pivotal role in many stages of carcinogenesis. Via EV-mediated communication, tumour cells can manipulate cells from host immune system or from the tumour microenvironment, and, ultimately, they promote tumour progression and modulate host immunity towards tumour’s favour. Additionally, the role of EVs in modulating resistance to pharmacological and radiological therapy of many cancer types has become evident lately. Our understanding of EV biology and their role in cancer promotion and drug resistance has evolved considerably in recent years. In this review, we specifically discuss the current knowledge on the association between EVs and gastrointestinal (GI) and liver cancers, including their potential for diagnosis and treatment.

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Serum Exosomal MicroRNA, miR-10b-5p, as a Potential Diagnostic Biomarker for Early-Stage Hepatocellular Carcinoma

Cited by 94 publications

References 27 publications

MiR‐10b inhibits migration and invasion of pancreatic ductal adenocarcinoma via regulating E2F7

MiR‐10b inhibits migration and invasion of pancreatic ductal adenocarcinoma via regulating E2F7

The Crosstalk between Tumor Cells and the Microenvironment in Hepatocellular Carcinoma: The Role of Exosomal microRNAs and Their Clinical Implications

EVs as Potential New Therapeutic Tool/Target in Gastrointestinal Cancer and HCC

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