Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma

Xue, Xiaofeng; Zhao, Yujun; Wang, Xiaona; Qin, Lei; Hu, Rongkuan

doi:10.1002/jcb.27165

Cited by 76 publications

(55 citation statements)

References 30 publications

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“…Strategies to improve this efficacy deserve investigation. For example, recent studies indicated that the measurement of miR-122 from circulating exosomes may provide better diagnostic efficacy for HCC than the measurement of miR-122 in serum [37,38]. Other strategies such as using miRNA panels [39] or combining conventional diagnostic strategies with circulating miR-122 measurement [40] may also improve the diagnostic efficacy for HCC.…”

Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA-122 for the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis

Zhao

Lin

et al. 2020

BioMed Research International

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Background. Circulating microRNA-122 (miR-122) has been recognized as a marker of hepatocellular carcinoma (HCC). The current meta-analysis was performed to quantitatively evaluate the diagnostic performance of circulating miR-122 for HCC. Methods. Related studies that evaluated the diagnostic performance of circulating miR-122 determined from pathophysiological examination for HCC were obtained by systematic searches of the PubMed and Embase databases. A randomized fixed effects model was applied according to the heterogeneity among studies. The pooled sensitivity, specificity, and area under the summary receiver operating characteristic curve (AUC) were calculated to evaluate the diagnostic accuracy. Publication bias was detected by Deeks' funnel plot asymmetry test. Results. Thirteen studies providing data for 920 HCC patients and 1217 controls were included in the meta-analysis. The pooled sensitivities, specificities, and AUCs of serum miR-122 were 0.76, 0.75, and 0.82, respectively, for discriminating HCC patients from overall controls; 0.85, 0.83, and 0.91, respectively, for discriminating HCC patients from healthy controls; 0.79, 0.82, and 0.87, respectively, for discriminating HCC from HBV or HCV infection; and 0.65, 0.75, and 0.74, respectively, for discriminating HCC from liver cirrhosis or dysplastic nodule formation. No significant publication bias was detected. Conclusions. Serum miR-122 confers moderate efficacy for discriminating HCC patients from healthy controls or patients with HBV or HCV infection, but not for discriminating HCC patients from those with liver cirrhosis or dysplastic nodule formation.

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Section: Discussionmentioning

confidence: 99%

Circulating MicroRNA-122 for the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis

Zhao

Lin

et al. 2020

BioMed Research International

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“…In the following year, Zhu et al discovered the role of miR-29a as a prognostic marker in HCC patients receiving surgical resection [35]. At present, growing body of evidence has shown the significance of miR-29a as a diagnostic/prognostic tool in HCC [41,42,47,50,55,[67][68][69][70] and alcoholic liver disease [71], as well as NAFLD. In 2017, Lopez-Riera et al identified circulating miR-29a as one predictor of miRNAs biomarker set in NAFLD patients [72].…”

Section: Mirs As Markers In Liver Diseasementioning

confidence: 99%

The Emerging Role of MicroRNAs in NAFLD: Highlight of MicroRNA-29a in Modulating Oxidative Stress, Inflammation, and Beyond

Lin

Yang

Wang

et al. 2020

Cells

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Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease and ranges from steatosis to steatohepatitis and to liver fibrosis. Lipotoxicity in hepatocytes, elevated oxidative stress and the activation of proinflammatory mediators of Kupffer cells, and fibrogenic pathways of activated hepatic stellate cells can contribute to the development of NAFLD. MicroRNAs (miRs) play a crucial role in the dysregulated metabolism and inflammatory signaling connected with NAFLD and its progression towards more severe stages. Of note, the protective effect of non-coding miR-29a on liver damage and its versatile action on epigenetic activity, mitochondrial homeostasis and immunomodulation may improve our perception of the pathogenesis of NAFLD. Herein, we review the biological functions of critical miRs in NAFLD, as well as highlight the emerging role of miR-29a in therapeutic application and the recent advances in molecular mechanisms underlying its liver protective effect.

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“…This indicates that miR-29a is involved in a variety of tumor progression processes and plays an important role in tumor growth, metastasis, apoptosis, and proliferation (19)(20)(21). As a member of the microRNA family, miR-29a has been expressed in many tumors and has a tumor suppressor effect (22)(23)(24), but its mechanism of action in liver cancer is worthy of further study.…”

Section: Introductionmentioning

confidence: 99%

TUG1 as ceRNA combined with miR-29a to promotes the expression of IFITM3 in hepatocellular carcinoma

Liu

Feng

Liao

et al. 2020

Preprint

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Background: Numerous studies have shown that TUG1 has an important relationship with tumorigenesis. TUG1 is highly expressed in most tumors and can promote tumor development. However, the role of TUG1 in hepatocellular carcinoma (HCC) remains to be studied. miR-29a plays a tumor suppressor role in a variety of tumors, and there is a relationship between TUG1 and miR-29a, but the specific relationship and mechanism of action are still unclear. miR-29a can inhibit the expression of IFITM3. However, the regulatory relationship between these three components requires elucidation. This study aimed to investigate the regulatory relationship between TUG1, miR-29a, and IFITM3 in human hepatocarcinogenesis.Methods: The expression levels of TUG1 and miR-29a in tumor tissues and adjacent non-tumor tissues of 41 HCC patients were detected by real-time quantitative polymerase chain reaction. The migration and invasion of liver cancer cells were studied by a wound healing assay and the Transwell method. The apoptosis rate of hepatocarcinoma cells was detected by flow cytometry, and the proliferation rate of hepatoma cells was detected by the EdU method. Immunofluorescence was selected to detect the expression of TUG1 and IFITM3 in HCC-LM3 and HL-7702. The relationship between TUG1 and miR-29a was detected using a double luciferase report and FISH. Tumors were established in vivo by subcutaneous injection of hepatocellular carcinoma cells into nude mice and injection of these cells into the tail vein. Western blotting was used to quantify the biomarkers. Results: TUG1 expression increased significantly in both tumor tissues and HCC cells. The expression of miR-29a in liver cancer tissues was also significantly lower than that in normal human liver tissues. The expression of TUG1 in HCC tissue samples was negatively correlated with that of miR-29a. Moreover, the expression of TUG1 was positively correlated with the expression of IFITM3. TUG1 can regulate the migration, invasion, apoptosis, and proliferation of HCC lines in vitro and regulate the development of tumors in vivo. Knocking down TUG1 will increase miR-29a expression, and thus, weaken the invasion, migration, and proliferation of HCC cells and enhance their apoptosis. miR-29a can affect the occurrence and progression of liver cancer through IFITM3. It was found that TUG1 regulates IFITM3 in HCC cells via miR-29a, and its expression affects cell invasion, migration, proliferation, and apoptosis.Conclusion: As a CeRNA, TUG1 competitively binds mir-29a to regulate IFITM3 and promote the development of liver cancer. Downregulation of TUG1 can significantly inhibit the migration, invasion, and proliferation of liver cancer cells, and TUG1 is expected to serve as a key gene to improve the prognosis of patients.

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Development and validation of serum exosomal microRNAs as diagnostic and prognostic biomarkers for hepatocellular carcinoma

Cited by 76 publications

References 30 publications

Circulating MicroRNA-122 for the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis

Circulating MicroRNA-122 for the Diagnosis of Hepatocellular Carcinoma: A Meta-Analysis

The Emerging Role of MicroRNAs in NAFLD: Highlight of MicroRNA-29a in Modulating Oxidative Stress, Inflammation, and Beyond

TUG1 as ceRNA combined with miR-29a to promotes the expression of IFITM3 in hepatocellular carcinoma

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