Role of exosomes and exosomal microRNAs in hepatocellular carcinoma: Potential in diagnosis and antitumour treatments (Review)

Pan, Jinghua; Zhou, Hong; Zhao, Xiaoxu; Ding, Hui; Li, Wei; Li, Qin; Pan, Yunlong

doi:10.3892/ijmm.2018.3383

Cited by 51 publications

(55 citation statements)

References 76 publications

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“…Recently, many studies have been performed on serum exo-miRs to detect novel biomarkers for HCC [25][26][27]. However, the diagnostic efficiencies of the previously evaluated serum exo-miRs have not been satisfactory for clinical application.…”

Section: Discussionmentioning

confidence: 99%

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

Cho

Eun

Baek

et al. 2020

JCM

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Exosomal microRNAs (exo-miRs) have been promising cancer biomarkers. MiRs in hepatocellular carcinoma (HCC) cell-derived exosomes (HEX) were analyzed to identify reliable serum biomarkers for HCC. To detect overexpressed miRs in HEX, extracted exosomal small RNAs from human HCC cell lines and normal hepatocytes were sequenced and analyzed. Clinical significance of the overexpressed miRs in HEX was evaluated using quantitative real-time PCR (qRT-PCR) on serum samples of a validation cohort consisting of 28 healthy individuals, 60 with chronic liver disease, and 90 with HCC. We found 49 significantly overexpressed miRs in HEX compared to a normal hepatocyte. Among them, miR-10b-5p, miR-18a-5p, miR-215-5p, and miR-940 were overexpressed in HCC tissues and also associated with prognosis of HCC in the analysis of a public omics database. qRT-PCR analysis of the four serum exo-miRs in the validation cohort revealed serum exo-miR-10b-5p as a promising biomarker for early-stage HCC with 0.934 area under the curve (AUC) (sensitivity, 90.7%; specificity, 75.0%; cutoff value, 1.8-fold). Overexpression of serum exo-miR-215-5p was found to be significantly associated with poor disease-free survival in patients with HCC. Serum exo-miR-10b-5p is a potential biomarker for early-stage HCC, while serum exo-miR-215-5p can be used as prognostic biomarker for HCC.

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Section: Discussionmentioning

confidence: 99%

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

Cho

Eun

Baek

et al. 2020

JCM

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“…miRNAs have been reported to play pivotal roles in regulating development, diagnosis, and antitumor treatments of HCC 21 . In this study, we found that miR-196a and miR-196b expressions were enhanced in HCC tissues and cells, which is also in agreement with previous efforts 10, 11 .…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

Ren

et al. 2019

Cell Death Dis

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microRNAs (miRNAs) play essential roles in progression of hepatocellular carcinoma (HCC). However, the roles of miR-196a and miR-196b as well as mechanism in HCC progression remain poorly understood. The expressions of miR-196a, miR-196b and suppressor of cytokine signaling 2 (SOCS2) were measured in HCC tissues and cells by quantitative realtime polymerase chain reaction or immunohistochemistry. HCC progression was investigated by cell proliferation, glycolysis, cycle, clones, apoptosis, and necrosis. The interaction between SOCS2 and miR-196a or miR-196b was explored by luciferase activity and RNA immunoprecipitation analyses. The expressions of proteins in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway were measured by western blot. A xenograft model was established to investigate the roles of miR-196a or miR-196b in vivo. We found that miR-196a and miR-196b were highly expressed in HCC tissues and cells. High expression of miR-196a or miR-196b was correlated with tumor size, tumor-node-metastasis stage, lymph node metastasis, albumin-bilirubin grade and poor 5-year survival. Knockdown of miR-196a or miR-196b suppressed cell proliferation, glycolysis, cell cycle process, colony formation but induced apoptosis or necrosis in HCC cells. SOCS2 was targeted by miR-196a and miR-196b and its interference ablated abrogation of miR-196a or miR-196b-mediated inhibitory effect on HCC progression. SOCS2 was negatively associated with activation of the JAK/STAT pathway. Besides, knockdown of miR-196a or miR-196b limited xenograft tumor growth by blocking the JAK/STAT pathway. We concluded that downregulation of miR-196a or miR-196b inhibited HCC progression through regulating the JAK/STAT pathway via targeting SOCS2, providing novel targets for prognosis and therapeutics of HCC.

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“…In human beings, the majority of miRNAs are located in introns or non-coding mRNA transcripts of protein-coding genes, while the remaining miRNAs are distant from the transcripts in the genome, such as the exons of non-coding mRNA genes, or 3' UTR of mRNA genes, or other miRNAs genes [3]. In recent years, more and more studies have proved that miRNAs play important roles in a variety of cancer progression, such as respiratory cancers [4], digestive system cancers [5,6], neurological system cancers [7], genitourinary cancers [8] and vascular cancers [9]. miRNAs regulate the proliferation, differentiation, invasion, apoptosis and metastasis process of cancer cells in the form of oncogenes or tumor suppressor genes [10,11].It is worth noting that miRNAs and their target mRNA play synergistic network roles in cancer progression, and the analyses of miRNA expressions have identified potential markers for the diagnosis, prognosis and treatment of cancer patients [12,13].In these respects, more and more studies have confirmed…”

Section: Introductionmentioning

confidence: 99%

Role of MicroRNA-30c in cancer progression

et al. 2020

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MicroRNAs (miRNAs or miRs) is a non-coding small RNA of a type of 18~24 nucleotide-regulated gene that has been discovered in recent years. It mainly degrades the target gene mRNA or inhibits its translation process through the complete or incomplete bindings with 3'UTR of target genes, followed by the regulation of individual development, apoptosis, proliferation, differentiation and other life activities through the post-transcriptional regulation. Among many miRNAs, the microRNA family, miR-30, plays diverse roles in these key process of neoplastic transformation, metastasis, and clinical outcomes in different cancer progression. As key member of miR-30, miR-30c is regulated by oncogenic transcription factors and cancer progression related genes. Recently, numerous studies have demonstrated that the aberrant expression of miR-30c was significantly associated with the majority of human cancer progression. In this review, the diverse roles of miR-30c in different cancer progression such as the cellular and molecular mechanisms, the potential applications in clinics were summarized to speculate the benefits of miR-30c over-expression in cancer treatment and prognosis.

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Role of exosomes and exosomal microRNAs in hepatocellular carcinoma: Potential in diagnosis and antitumour treatments (Review)

Cited by 51 publications

References 76 publications

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

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

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2

Role of MicroRNA-30c in cancer progression

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