microRNAs In Hepatocellular Carcinoma Research Articles

Exosomal microRNAs in hepatocellular carcinoma, rising research filed in hepatocellular carcinoma

In this editorial we comment on the review by Wang et al published in the recent issue of the World Journal of Gastroenterology in 2023. Small extracellular vesicles (exosomes) play important roles in the tumor microenvironment. In this review, the authors introduce the following points: (1) The composition and function of exosomal microRNAs (miRNAs) of different cell origins in hepatocellular carcinoma (HCC); (2) the crosstalk between exosomal miRNAs from stromal cells and immune cells in the tumor microenvironment and the progression of HCC; and (3) the potential applicability of exosomal miRNAs derived from mesen-chymal stem cells in the treatment of HCC. In addition, the potential applicability of exosomal miRNAs derived from mesenchymal stem cells in the treatment of HCC was introduced. In this review, the authors give us an overview of the exosomal RNA and summarize the function of exosomal RNA in HCC, which provides a deeper understanding of exosomal miRNAs to the readers.

What are the changes in the hotspots and frontiers of microRNAs in hepatocellular carcinoma over the past decade?

Emerging research suggests that microRNAs (miRNAs) play an important role in the development of hepatocellular carcinoma (HCC). A comprehensive analysis of recent research concerning miRNAs in HCC development could provide researchers with a valuable reference for further studies. To make a comprehensive analysis of recent studies concerning miRNAs in HCC. All relevant publications were retrieved from the Web of Science Core Collection database. Bibliometrix software, VOSviewer software and CiteSpace software were used to visually analyze the distribution by time, countries, institutions, journals, and authors, as well as the keywords, burst keywords and thematic map. A total of 9426 publications on this topic were found worldwide. According to the keywords analysis, we found that the studies of miRNAs focused on their expression level, effects, and mechanisms on the biological behaviour of HCC. Keywords bursting analysis showed that in the early years (2013-2017), "microRNA expression", "gene expression", "expression profile", "functional polymorphism", "circulating microRNA", "susceptibility" and "mir 21" started to attract attention. In the latest phase (2018-2022), the hot topics turned to "sorafenib resistance", "tumor microenvironment" and so on. This study provides a comprehensive overview of the role of miRNAs in HCC development based on bibliometric analysis. The hotspots in this field focus on miRNAs expression level, effects, and mechanisms on the biological behavior of HCC. The frontiers turned to sorafenib resistance, tumor microenvironment and so on.

MicroRNAs in Hepatocellular Carcinoma: Insights into Regulatory Mechanisms, Clinical Significance, and Therapeutic Potential.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transformation (EMT), invasion, metastasis, metabolism, and drug resistance are the main factors affecting the development and treatment of tumors. MiRNAs play crucial roles in almost all major cellular biological processes. Studies have been carried out on miRNAs as biomarkers and therapeutic targets. Their dysregulation contributes to the progression and prognosis of HCC. This review aims to explore the molecular cascades and corresponding phenotypic changes caused by aberrant miRNA expression and their regulatory mechanisms, summarize and analyze novel biomarkers from somatic fluids (plasma/serum/urine), and highlight the latent capacity of miRNAs as therapeutic targets.

Research on the application of microRNA in hepatocellular carcinoma

The digestive tract frequently develops the malignant tumor known as hepatocellular carcinoma (HCC). A variety of liver diseases can develop into HCC and therefore a therapeutic approach is required. Extracellular vesicles known as exosomes are released by a number of cells and contain a wide range of active substances, including lipids, proteins, RNA, and DNA. microRNA is a type of RNA that accelerates apoptosis by participating in the regulation of downstream gene translation. Studies have shown that exosomal micrornas regulate HCC. Exosomal microRNAs have been proven in studies which regulate HCC. Exosomal micrornas may therefore be particular biomarkers for HCC metastases and early diagnosis as well as possible therapeutic targets. The utilization of exosomal micrornas in HCC is employed as biomarkers for early diagnosis and may trigger cancer cell apoptosis through the PI3K-AKT channel or MAPKs/ERK channel to produce therapeutic effects. Exosomal micrornas are briefly detailed in this paper.

An Insight into the Arising Role of MicroRNAs in Hepatocellular Carcinoma: Future Diagnostic and Therapeutic Approaches.

Hepatocellular carcinoma (HCC) constitutes a frequent highly malignant form of primary liver cancer and is the third cause of death attributable to malignancy. Despite the improvement in the therapeutic strategies with the exploration of novel pharmacological agents, the survival rate for HCC is still low. Shedding light on the multiplex genetic and epigenetic background of HCC, such as on the emerging role of microRNAs, is considered quite promising for the diagnosis and the prediction of this malignancy, as well as for combatting drug resistance. MicroRNAs (miRNAs) constitute small noncoding RNA sequences, which play a key role in the regulation of several signaling and metabolic pathways, as well as of pivotal cellular functions such as autophagy, apoptosis, and cell proliferation. It is also demonstrated that miRNAs are significantly implicated in carcinogenesis, either acting as tumor suppressors or oncomiRs, while aberrations in their expression levels are closely associated with tumor growth and progression, as well as with local invasion and metastatic dissemination. The arising role of miRNAs in HCC is in the spotlight of the current scientific research, aiming at the development of novel therapeutic perspectives. In this review, we will shed light on the emerging role of miRNAs in HCC.

Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications.

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers worldwide and is characterized by complex molecular carcinogenesis. Neuropilins (NRPs) NRP1 and NRP2 are the receptors of multiple proteins involved in key signaling pathways associated with tumor progression. We aimed to systematically review all the available findings on their role in HCC. We searched the Scopus, Web of Science (WOS), PubMed, Cochrane and Embase databases for articles evaluating NRPs in preclinical or clinical HCC models. This study was registered in PROSPERO (CRD42022349774) and include 49 studies. Multiple cellular and molecular processes have been associated with one or both NRPs, indicating that they are potential diagnostic and prognostic biomarkers in HCC patients. Mainly NRP1 has been shown to promote tumor cell survival and progression by modulating several signaling pathways. NRPs mainly regulate angiogenesis, invasion and migration and have shown to induce invasion and metastasis. They also regulate the immune response and tumor microenvironment, showing a crucial interplay with the hypoxia response and microRNAs in HCC. Altogether, NRP1 and NRP2 are potential biomarkers and therapeutic targets, providing novel insight into the clinical landscape of HCC patients.

The role of microRNAs in hepatocellular carcinoma: Therapeutic targeting of tumor suppressor and oncogenic genes.

Hepatocellular carcinoma (HCC) is a severe malignant liver cancer with a poor prognosis and a high mortality rate. This carcinoma is a multistage process that begins with chronic hepatitis and progresses to cirrhosis, dysplastic nodules, and eventually HCC. However, the exact molecular etiology remains unclear. MicroRNAs (miRs) are small non-coding RNAs that modulate the expression of numerous genes. These molecules have become significant participants in several functions, including cell proliferation, differentiation, development, and tumorrelated properties. They have a pivotal role in carcinogenesis as oncogenes or tumor suppressor genes. Furthermore, some investigations have shown that particular miRs might be used as predictive or diagnostic markers and therapeutic targets in HCC therapy. This review study summarizes the current level of knowledge on the role of miRs in the initiation and progression of HCC.

MicroRNA214 expression inhibits HCC cell proliferation through PTK2b/ Pyk2.

MicroRNAs (miRNAs/miRs) are crucial regulatory molecules that act as the most significantly downregulated microRNAs in hepatocellular carcinoma (HCC). PTK2b/Pyk2 is a non-receptor protein tyrosine kinase, which plays an important role in the development and metastasis of cancer. In this study, we explored the expression level and functional relationship between MicroRNA-214 (miR-214) and PTK2b/ Pyk2 in liver cancer cells. For this purpose, we analyzed the expression of miR-214 and PTK2b/Pyk2 in 38 cases of HCC and paired non-neoplastic tissue specimens using real-time PCR. MTT, cell cycle and construct recombinant plasmids analysis were used to explore the effects of miR-214 and PTK2b/Pyk2 on liver cancer cell proliferation. Results showed that the expression level of mir-214 in liver cancer tissues and liver cancer cell lines was significantly lower than that in normal tissues and cells, while the expression of PTK2b/Pyk2 was significantly increased. The overexpression of mir-214 or inhibition PTK2b/Pyk2 inhibited the proliferation of HCC cells. This research showed that mir-214 has an inhibitory effect on liver cancer through the expression of PTK2b/Pyk2.

MicroRNA in HCC: Biomarkers and Therapeutic Targets

Hepatocellular carcinoma (HCC) is a malignant tumor with high morbidity and mortality. At present, diagnostic methods such as imaging observation, serum testing and tissue biopsy, as well as treatment methods such as surgical resection, radiotherapy, and chemotherapy have certain limitations in clinical interventions for HCC due to the complex pathogenesis and drug resistance of liver cancer, which seriously affect the survival and prognosis of patients. As a large-scale cytokine, microRNA (miRNA) plays an important role in regulating various life activities of cells. Extensive evidence proved that certain miRNAs are specifically expressed in the tissues and blood of HCC patients, and some of them have been confirmed as important factors that can participate in the regulation of key signaling pathways in cancer cells. For this reason, these miRNAs have great potential in clinical diagnosis and treatment of HCC, and can improve the limitations of conventional diagnosis and treatment. Our paper reviews the research on miRNA biomarkers and targets in HCC in recent years, and aims to provide new ideas for the diagnosis and treatment of HCC.

Transcriptome analysis revealed key prognostic genes and microRNAs in hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, the molecular mechanisms involved in HCC remain unclear and are in urgent need of elucidation. Therefore, we sought to identify biomarkers in the prognosis of HCC through an integrated bioinformatics analysis.MethodsMessenger RNA (mRNA) expression profiles were obtained from the Gene Expression Omnibus database and The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) for the screening of common differentially expressed genes (DEGs). Function and pathway enrichment analysis, protein-protein interaction network construction and key gene identification were performed. The significance of key genes in HCC was validated by overall survival analysis and immunohistochemistry. Meanwhile, based on TCGA data, prognostic microRNAs (miRNAs) were decoded using univariable and multivariable Cox regression analysis, and their target genes were predicted by miRWalk.ResultsEleven hub genes (upregulated ASPM, AURKA, CCNB2, CDC20, PRC1 and TOP2A and downregulated AOX1, CAT, CYP2E1, CYP3A4 and HP) with the most interactions were considered as potential biomarkers in HCC and confirmed by overall survival analysis. Moreover, AURKA, PRC1, TOP2A, AOX1, CYP2E1, and CYP3A4 were considered candidate liver-biopsy markers for high risk of developing HCC and poor prognosis in HCC. Upregulation of hsa-mir-1269b, hsa-mir-518d, hsa-mir-548aq, hsa-mir-548f-1, and hsa-mir-6728, and downregulation of hsa-mir-139 and hsa-mir-4800 were determined to be risk factors of poor prognosis, and most of these miRNAs have strong potential to help regulate the expression of key genes.ConclusionsThis study undertook the first large-scale integrated bioinformatics analysis of the data from Illumina BeadArray platforms and the TCGA database. With a comprehensive analysis of transcriptional alterations, including mRNAs and miRNAs, in HCC, our study presented candidate biomarkers for the surveillance and prognosis of the disease, and also identified novel therapeutic targets at the molecular and pathway levels.

MicroRNA and liver cancer.

Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. HCC is characterized by a poor prognosis and an ever increasing number of scientific studies aim to find new diagnostic, prognostic, and therapeutic targets. MicroRNAs (miRNAs), small non-coding RNAs that regulate the gene expression in many processes, have been shown to play a crucial role in regulating hepatocellular carcinoma. miRNAs may act as oncogenic miRNAs and tumor suppressor miRNAs and regulate cancer cell proliferation, invasion, and metastasis by being differently upregulated or downregulated and targeting the genes related with carcinogenesis. miRNAs secreted from cancer cells are found circulating in the blood, presenting an opportunity for their use as disease-related biomarkers. Moreover, extracellular vesicle-derived miRNAs are known to reflect the cell of origin and function and may provide effective biomarkers for predicting diagnosis and prognosis and new therapeutic target in HCC. In this article, we describe the most recent findings regarding the molecular mechanisms and gene regulation of microRNA in HCC, as well as their application in diagnosis/prognosis and treatment.

Regulation of mTOR singnaling pathway by microRNA in hepatocellular carcinoma

MicroRNA (miRNA) is a non-coding small molecule RNA, which is involved in the occu-rrence and development of tumor as an oncogene or tumor suppressor gene. The abnormal expression of many kinds of miRNAs in hepatocellular carcinoma (HCC) can directly or indirectly act on PI3K, Akt, mTOR, IGF-1R, TGF-β and other signal molecules in mTOR signal pathway, they are crucial in the appreciation, invasion and metastasis of HCC cells. Key words: Carcinoma, hepatocellular; MicroRNAs; TOR serine-threonine kinases

Integrated analysis of clinical significance and functional involvement of microRNAs in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common lethal cancers worldwide. To explore the potential prognosis-associated microRNAs (miRNAs) for HCC patients, we performed integrated analyses on the miRNA expression profiles fromThe Cancer Genome Atlas project. Genome-wide overall survival (OS)- and progression-free survival (PFS)-associated miRNA screening were performed by multivariate Cox proportional hazards regression analyses. A five-miRNA expression signature (miR-148a, miR-3677-3p, miR-744*, miR-210, and miR-3613-5p) was identified as an indicator for HCC OS (p < .0001; hazard ratio [HR] = 2.631). In addition, a seven-miRNA expression signature (miR-127-5p, miR-146a, miR-152, miR-193a-3p, miR-331-5p, miR-500a*, and miR-550a*) was identified as a predictor for HCC PFS (p < .0001; HR = 2.608). This systematic analysis suggested that both the OS- and PFS-associated signatures have better performance in HCC survival prediction than the conventional clinicopathological parameters. Further functional enrichment analysis of the corresponding genes targeted by these signature miRNAs revealed their biological significance in the PI3K-Akt signaling pathway. In conclusion, our present study identified a five-miRNA OS-associated signature and a seven-miRNA PFS-associated signature as HCC prognostic biomarkers with potential clinical significance, which could enable the development of novel targeted therapeutic strategies for HCC treatment.

Detection of DNA methylated microRNAs in hepatocellular carcinoma

Irregular methylation, including DNA hypomethylation and/or promoter gene CpG hypermethylation, is involved in the pathogenesis of several solid tumors, including liver cancer. miRNAs are small, endogenous, noncoding RNAs that serve as posttranscriptional regulators of gene expression. Previous research has focused on identifying the factors that regulate the expression of miRNAs in hepatic carcinogenesis. The factors that regulate miRNA expression are not clear; in particular, the role of DNA methylation, an epigenetic regulatory factor that controls miRNA transcription, has not been clarified. The goal of this study is to explore our understanding of the mechanism by which HCC may develop and progress through identification of the role of epigenetically regulated miRNAs influences in the liver carcinogenesis. The current study included 60 patients who were well diagnosed as HCC patients. 60 patients who suffer from liver cirrhosis were also enrolled in the current study and 30 healthy control subjects who serve as control group. All patients will be subjected to: full clinical assessment, abdominal ultrasound, Blood sample will be withdrawn from every patients for both biochemical and serum detection of microRNAs (191-203 -335) by real time PCR. We found that all studied microRNAs were down regulated among HCC patients when compared to cirrhotic patients and controls (p value: 0.005, 0.005 and 0.001 for microRNAs 191, 203 and 335 respectively). Moreover, these microRNAs can discriminate cases of HCC from risky cirrhotic patients. We can conclude that downregulated microRNAs among HCC cases proposed a pattern to explain the role of DNA methylation on miRNA and gene expression in HCC.

Expression Profiles Analysis Identification and Interaction of Key Genes and Micrornas in Hepatocellular Carcinoma

Background: Hepatocellular carcinoma is one of the most common malignant tumors, with rapid development and high malignancy. MicroRNAs have been reported to play important roles in hepatocellular carcinoma progression. Aim: To identify the key genes and miRNAs in HCC, and to explore their potential molecular mechanisms. Methods: Gene expression profiles of GSE15471 (mRNA profile) and GSE57555 (miRNA profile) were downloaded from gene expression omnibus, which were analysed using R software and bioconductor packages. The gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichments of DEGs were performed using the DAVID database, and the protein–protein interaction networks of the DEGs were constructed from the STRING database. In addition, targets of differentially expressed miRNAs were predicted by the online resource miRDB. Result: In total, 191 differentially expressed genes were identified, including 142 upregulated and 49 downregulated genes. Functional analysis revealed that these DEGs were associates with wound healing, endodermal cell-cell adhesion, activation of MAPK activity and negative regulation of cell proliferation. In addition, we identified five DEMs, which were upregulated and downregulated. hsa-miR-122-5p may target the PDK4, and hsa-miR-21-5p probably targets SPOCK1 and PAIP2B. Conclusions: We applied integrated bioinformatics to identify key pathogenic genes involved in hepatocellular carcinoma and provide new clues for further studies of hepatocellular carcinoma.

Identification of invasion-metastasis-associated microRNAs in hepatocellular carcinoma based on bioinformatic analysis and experimental validation

BackgroundHepatocellular carcinoma (HCC) is one of the most lethal cancer, mainly attributing to its high tendency to metastasis. Vascular invasion provides a direct path for solid tumor metastasis. Mounting evidence has demonstrated that microRNAs (miRNAs) are related to human cancer onset and progression including invasion and metastasis.MethodsIn search of invasion-metastasis-associated miRNAs in HCC, microarray dataset GSE67140 was downloaded from the Gene Expression Omnibus database. Differentially expressed miRNAs (DE-miRNAs) were obtained by R software package and the potential target genes were predicted by miRTarBase. The database for annotation, visualization and integrated discovery (DAVID) was introduced to perform functional annotation and pathway enrichment analysis for these potential targets of DE-miRNAs. Protein–protein interaction (PPI) network was established by STRING database and visualized by Cytoscape software. The effects of the miR-494-3p and miR-126-3p on migration and invasion of HCC cell lines were evaluated by conducting wound healing assay and transwell assay.ResultsA total of 138 DE-miRNAs were screened out, including 57 upregulated miRNAs and 81 downregulated miRNAs in human HCC tumors with vascular invasion compared with human HCC tumors without vascular invasion. 762 target genes of the top three upregulated and downregulated miRNAs were predicted, and they were involved in HCC-related pathways, such as pathway in cancer, focal adhesion and MAPK signaling pathway. In the PPI network, the top 10 hub nodes with higher degrees were identified as hub genes, such as TP53 and MYC. Through constructing the miRNA-hub gene network, we found that most of hub genes could be potentially modulated by miR-494-3p and miR-126-3p. Of note, miR-494-3p and miR-126-3p was markedly upregulated and downregulated in HCC cell lines and tissues, respectively. In addition, overexpression of miR-494-3p could significantly promote HCC migration and invasion whereas overexpression of miR-126-3p exerted an opposite effect.ConclusionsTargeting miR-494-3p and miR-126-3p may provide effective and promising approaches to suppress invasion and metastasis of HCC.

Identification of molecular target genes and key pathways in hepatocellular carcinoma by bioinformatics analysis.

Background and aimHepatocellular carcinoma (HCC) is a major cause of cancer mortality and is increasing incidence worldwide. The aim of this study was to identify the key genes and microRNAs in HCC and explore their potential mechanisms.MethodsThe gene expression profiles of GSE76427, GSE64041, GSE57957, and the microRNA dataset GSE67882 were downloaded from the Gene Expression Omnibus database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs) and miRNAs (DEMs). The gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis were performed for DEGs using the Database for Annotation, Visualization, and Integrated Discovery. A protein–protein interaction (PPI) network of the DEGs was constructed by Search Tool for the Retrieval of Interacting Genes and visualized by Cytoscape. Moreover, miRecords was used to predict the target genes of DEMs.ResultsIn total, 106 DEGs were screened out in HCC, consisting of 89 upregulated genes and 17 downregulated genes, which were mainly enriched in biological processes associated with oxidation–reduction process. Besides, the Kyoto Encyclopedia of Genes and Genomes pathways including chemical carcinogenesis, drug metabolism-cytochrome P450, tryptophan metabolism, and retinol metabolism were involved. A PPI network was constructed consisting of 105 nodes and 66 edges. A significant module including nine hub genes, ASPM, AURKA, CCNB2, CDKN3, MELK, NCAPG, NUSAP1, PRC1, and TOP2A, was detected from the PPI network by Molecular Complex Detection. The enriched functions were mainly associated with the mitotic cell cycle process, cell division, and mitotic cell cycle. In addition, a total of 21 DEMs were identified, including 9 upregulated and 12 downregulated miRNAs. Interestingly, ZBTB41 was the potential target of seven miRNAs. Finally, the nine hub genes and three miRNA-target genes expression levels were validated by reverse transcription-polymerase chain reaction. The relative expression levels of nine genes (ASPM, AURKA, CDKN3, MELK, NCAPG, PRC1, TOP2A, ZBTB41, and ZNF148) were significantly upregulated in cancer tissues.ConclusionThis study identified the key genes and potential molecular mechanisms underlying the development of HCC, which could provide new insight for HCC interventional strategies.

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

Communication between hepatocellular carcinoma (HCC) cells and their environment is essential for the development and progression of HCC. Exosomes, which are microvesicles secreted by a number of cell types, are carriers of intercellular information and regulate the tumour microenvironment. Studies have demonstrated that exosomes are involved in the communication between HCC cells, endothelial cells and stem cells, and that they serve important roles in the metastasis and invasion, immune evasion and immunotherapy of HCC. In addition, the mechanism of HCC-derived exosome-mediated microRNA (miRNA) transfer is important in the environmental modulation of HCC growth and progression. As exosomes can be used for detecting and monitoring HCC, they can potentially serve as specific biomarkers for early-stage tumours and the tumour metastasis of HCC. Moreover, mesenchymal stem cell-derived exosomes can be transfected with miRNAs to inhibit HCC development. Therefore, as nucleic acid delivery vehicles, exosomes show a tremendous potential for effective treatment against HCC. In the present review, recent advances in our understanding of the source, composition and function of exosomes in HCC, and their potential value in the early diagnosis and treatment of HCC, are summarized.

The Role of MicroRNAs in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one of the most common cancers, leading to the second cancer-related death in the global. Although the treatment of HCC has greatly improved over the past few decades, the survival rate of patients is still quite low. Thus, it is urgent to explore new therapies, especially seek for more accurate biomarkers for early diagnosis, treatment and prognosis in HCC. MicroRNAs (miRNAs), small noncoding RNAs, are pivotal participants and regulators in the development and progression of HCC. Great progress has been made in the studies of miRNAs in HCC. The key regulatory mechanisms of miRNAs include proliferation, apoptosis, invasion, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, drug resistance and autophagy in HCC. And exosomal miRNAs also play important roles in proliferation, invasion, metastasis, and drug resistance in HCC by regulating gene expression in the target cells. In addition, some miRNAs, including exosomal miRNAs, can be as potential diagnostic and prediction markers in HCC. This review summarizes the latest researches development of miRNAs in HCC in recent years.

Exosomal miR-9-3p suppresses HBGF-5 expression and is a functional biomarker in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer and the third leading cause of cancer-related death worldwide. Exosomes are secreted membrane vesicles that play important roles in various diseases by transporting proteins and RNAs, including microRNAs, between cells. However, the function of exosomal miRNA in HCC has not been fully investigated. Exosomes were obtained from the sera by ultracentrifugation and were processed for transmission electron microscopy (TEM). Real time PCR were revealed changes of miRNA between patients and normal donors. Predicted targets of miRNA were described by bioinformatics analysis, luciferase reporter assay was used to confirmed whether miR-9-3p regulates target expression. And then miRNA were over-expressed in HCC cell line to study its function, western blotting were used to test expression of miRNA targets, Cell viability and proliferation were analyzed after over-expressed miR-9-3p using MTT and BrdU assay. Serum exosomes from patients with HCC contained significantly lower levels of the miR-9-3p than did serum exosomes from normal donors, suggesting a potential role for this microRNA in HCC. Bioinformatics analysis identified fibroblast growth factor 5 (HBGF-5), which plays an important role in cell proliferation, as a potential miR-9-3p target mRNA. Luciferase reporter assay confirming that miR-9-3p can directly regulate HBGF-5 expression. Consistent with this finding, overexpression of miR-9-3p in three HCC cell lines significantly downregulated HBGF-5 expression at both the mRNA and protein levels. Finally, overexpression of miR-9-3p reduced HCC cell viability and proliferation, and additionally reduced ERK1/2 expression, suggesting a potential mechanism by which miR-9-3p acts. These results provide new insight into the functions of miR-9-3p and HBGF-5 in HCC and identify miR-9-3p as a potential therapeutic target for HCC.