• Apatinib
• Cabozantinib
• Donafenib
• Hepatocellular carcinoma
• Lenvatinib
• Regorafenib
• Sorafenib
• Systemic therapy
• Tyrosine kinase inhibitor

• JYHL2021MS26 Lin He's Academician Workstation of New Medicine and Clinical Translation in Jining Medical University
• 2021YFA1101501 The National Key Research and Development Program of China
• 82172083 The National Natural Science Foundation of China

• IMbrave150 trial
• hepatocellular carcinoma
• immune-checkpoint inhibitors
• immunotherapy
• neoadjuvant therapy

• biomarkers
• hepatocellular carcinoma
• immune checkpoint inhibitors
• tyrosine kinase inhibitors

• Biomarkers
• Frailty
• Physical Activity
• Rehabilitation
• Sarcopenia
• microRNA

• HCC
• HCV
• HCV-induced HCC
• PNPLA3
• biomarker
• diagnostic
• miR-516a-3P
• polymorphism
• prognostic

Molecular biomarkers play a marginal role in clinical practice for hepatocellular carcinoma (HCC) diagnosis, surveillance and treatment monitoring. Radiological biomarker: alpha-fetoprotein is still a lone protagonist in this field. The potential role of molecular biomarkers in the assessment of prognosis and treatment results could reduce the health costs faced by standard radiology. The majority of efforts are oriented towards early HCC detection, but the field faces an important challenge to find adequate biomarkers for advanced HCC management.

Hepatocellular carcinoma (HCC) is the sixth most common malignancy worldwide and the fourth cause of tumor-related death. Imaging biomarkers are based on computed tomography, magnetic resonance, and contrast-enhanced ultrasound, and are widely applied in HCC diagnosis and treatment monitoring. Unfortunately, in the field of molecular biomarkers, alpha-fetoprotein (AFP) is still the only recognized tool for HCC surveillance in both diagnostic and follow-up purposes. Other molecular biomarkers have little roles in clinical practice regarding HCC, mainly for the detection of early-stage HCC, monitoring the response to treatments and analyzing tumor prognosis. In the last decades no important improvements have been achieved in this field and imaging biomarkers maintain the primacy in HCC diagnosis and follow-up. Despite the still inconsistent role of molecular biomarkers in surveillance and early HCC detection, they could play an outstanding role in prognosis estimation and treatment monitoring with a potential reduction in health costs faced by standard radiology. An important challenge resides in identifying sufficiently sensitive and specific biomarkers for advanced HCC for prognostic evaluation and detection of tumor progression, overcoming imaging biomarker sensitivity. The aim of this review is to analyze the current molecular and imaging biomarkers in advanced HCC.

Thyroid hormones (THs) inhibit hepatocellular carcinoma (HCC) through different mechanisms. However, whether microRNAs play a role in the antitumorigenic effect of THs remains unknown.

By next generation sequencing (NGS) we performed a comprehensive comparative miRNomic and transcriptomic analysis of rat hepatic preneoplastic lesions exposed or not to a short-term treatment with triiodothyronine (T3). The expression of the most deregulated miRs was also investigated in rat HCCs, and in human hepatoma cell lines, treated or not with T3.

Among miRs down-regulated in preneoplastic nodules following T3, co-expression networks revealed those targeting thyroid hormone receptor-β (Thrβ) and deiodinase1, and Oxidative Phosphorylation. On the other hand, miRs targeting members of the Nrf2 Oxidative Pathway, Glycolysis, Pentose Phosphate Pathway and Proline biosynthesis – all involved in the metabolic reprogramming displayed by preneoplastic lesions– were up-regulated. Notably, while the expression of most miRs deregulated in preneoplastic lesions was not altered in HCC or in hepatoma cells, miR-182, a miR known to target Dio1 and mitochondrial complexes, was down-deregulated by T3 treatment at all stages of hepatocarcinogenesis and in hepatocarcinoma cell lines. In support to the possible critical role of miR-182 in hepatocarcinogenesis, exogenous expression of this miR significantly impaired the inhibitory effect of T3 on the clonogenic growth capacity of human HCC cells.

This work identified several miRNAs, so far never associated to T3. In addition, the precise definition of the miRNA-mRNA networks elicited by T3 treatment gained in this study may provide a better understanding of the key regulatory events underlying the inhibitory effect of T3 on HCC development. In this context, T3-induced down-regulation of miR-182 appears as a promising tool.

• Associazione Italiana per la Ricerca sul Cancro
• Regione Autonoma della Sardegna

Hepatocellular carcinoma (HCC) is the fifth most common cancer. Differential expression of microRNAs (miRNAs)-326, miRNA-424, and miRNA-511 has been associated with the diagnosis and prognosis of HCC in different populations. However, limited information is available regarding their expression in Egyptian HCC patients.

To assess the role of circulating miRNAs-326, miRNA-424, and miRNA-511 in Egyptian HCC patients.

This prospective observational study included 70 HCC patients and 25 healthy controls. The circulating levels of these three miRNAs were evaluated by real-time PCR. Receiver operating characteristic curve analysis was used to test the diagnostic accuracy of microRNA expression levels.

All miRNAs were differentially expressed in HCC patients; miRNAs326 and miRNA-424 were upregulated, while miRNA-511 was downregulated. Both miRNA-326 and miRNA-424 showed sensitivity and specificity of 97%, 71.4%, and 52%, 60%, respectively, to differentiate HCC from controls. Moreover, miRNA-326 was associated with survival and could differentiate between Child grades (A vs B); miRNA-424 significantly differentiated early vs intermediate stages of HCC; while miRNA-511 was significantly correlated with response to modified Response Evaluation Criteria in Solid Tumors (mRECIST).

We conclude that miRNA-326, miRNA-424, and miRNA-511 have diagnostic and prognostic roles in Egyptian patients with hepatitis C virus-related HCC and should be considered for better disease management.

• Hepatocellular carcinoma
• miRNAs-326
• miRNA-424
• miRNA-511
• Modified response evaluation criteria in solid tumors

Extracellular vesicles (EVs), defined as intercellular messengers that carry their cargos between cells, are involved in several physiological and pathological processes. These small membranous vesicles are released by most cells and contain biological molecules, including nucleic acids, proteins and lipids, which can modulate signaling pathways of nearby or distant recipient cells. Exosomes, one the most characterized classes of EVs, include, among others, microRNAs (miRNAs), small non-coding RNAs able to regulate the expression of several genes at post-transcriptional level. In cancer, exosomal miRNAs have been shown to influence tumor behavior and reshape tumor microenvironment. Furthermore, their possible involvement in drug resistance mechanisms has become evident in recent years. Hepatocellular carcinoma (HCC) is the major type of liver cancer, accounting for 75-85% of all liver tumors. Although the improvement in HCC treatment approaches, low therapeutic efficacy in patients with intermediate-advanced HCC is mainly related to the development of tumor metastases, high risk of recurrence and drug resistance. Exosomes have been shown to be involved in pathogenesis and progression of HCC, as well as in drug resistance, by regulating processes such as cell proliferation, epithelial-mesenchymal transition and immune response. Herein, we summarize the current knowledge about the involvement of exosomal miRNAs in HCC therapy, highlighting their role as modulators of therapeutic response, particularly chemotherapy and immunotherapy, as well as possible therapeutic tools.

The progression of anchorage-dependent epithelial cells to anchorage-independent growth represents a critical hallmark of malignant transformation. Using an in vitro model of human papillomavirus (HPV)-induced transformation, we previously showed that acquisition of anchorage-independent growth is associated with marked (epi)genetic changes, including altered expression of microRNAs. However, the laborious nature of the conventional growth method in soft agar to measure this phenotype hampers a high-throughput analysis. We developed alternative functional screening methods using 96- and 384-well ultra-low attachment plates to systematically investigate microRNAs regulating anchorage-independent growth. SiHa cervical cancer cells were transfected with a microRNA mimic library (n = 2019) and evaluated for cell viability. We identified 84 microRNAs that consistently suppressed growth in three independent experiments. Further validation in three cell lines and comparison of growth in adherent and ultra-low attachment plates yielded 40 microRNAs that specifically reduced anchorage-independent growth. In conclusion, ultra-low attachment plates are a promising alternative for soft-agar assays to study anchorage-independent growth and are suitable for high-throughput functional screening. Anchorage independence suppressing microRNAs identified through our screen were successfully validated in three cell lines. These microRNAs may provide specific biomarkers for detecting and treating HPV-induced precancerous lesions progressing to invasive cancer, the most critical stage during cervical cancer development.

• anchorage-independent growth
• cervical cancer
• miRNA screen
• soft-agar assays
• ultra-low attachment

• SIRT1
• autophagy
• lipophagy
• liver cancer
• miR-425

• AKT/ERK/NFκB pathway
• BTG2
• CPSF6
• Glycolysis
• Hepatocellular carcinoma cells

• biliary tract cancers
• biomarker
• cholangiocarcinoma
• hepatocellular carcinoma
• immune checkpoint inhibitor
• targeted therapy

• Sorafenib
• aerobic glycolysis
• biomarker
• hepatocellar carcinoma
• prognosis

• Apoptosis
• Cytotoxicity
• Gastric cancer
• Immune escape
• Long intergenic noncoding RNA00936
• MicroRNA-425-3p
• Migration
• Monocyte chemotactic protein-induced protein 1

• Cell Line, Tumor
• Female
• Gene Silencing
• Humans
• Male
• MicroRNAs/genetics
• Middle Aged
• RNA, Long Noncoding/genetics
• Ribonucleases/genetics
• Stomach Neoplasms/genetics
• Stomach Neoplasms/immunology
• Transcription Factors/genetics
• Tumor Escape/genetics

Emerging articles have profiled the relations between microRNAs and viral myocarditis. This research was unearthed to explore the capacity of miR‐425‐3p on cardiomyocyte apoptosis in mice with viral myocarditis and its mechanism.

A total of 120 mice were classified into 4 groups in a random fashion (n = 30). The mice were intraperitoneally injected with coxsackievirus type B3 (CVB3) to induce myocarditis. On the 7th day after CVB3 infection, 10 mice in each group were euthanized to assess the heart function indices of mice, observe the pathological conditions, detect myocardial tissue apoptosis, and measure the inflammatory factor levels in myocardial tissues. Expression of miR‐425‐3p, transforming growth factor (TGF‐β1), and apoptosis‐associated proteins in myocardial tissues was determined. The remaining 20 mice in each group were used for survival observation. The luciferase activity assay was implemented to validate the relationship between miR‐425‐3p and TGF‐β1. miR‐425‐3p mimic was transfected into mouse cardiomyocytes HL‐1 and then infected with CVB3 to further verify the regulatory effect of miR‐425‐3p on the cardiomyocyte apoptosis in viral myocarditis.

miR‐425‐3p was lowly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR‐425‐3p improved the cardiac function, alleviated pathological conditions, reduced cardiomyocyte apoptosis, decreased Bax and cleaved Caspase‐3 expression, elevated Bcl‐2 expression, decreased levels of inflammatory factors and improved survival rate of mice with viral myocarditis. Luciferase activity assay verified that miR‐425‐3p could bind to TGF‐β1, and overexpressed miR‐425‐3p suppressed TGF‐β1, p‐smad2/smad2 and p‐smad3/smad3 expression. In vitro experiments further verified that overexpression of miR‐425‐3p inhibited the apoptosis of CVB3‐HL‐1 cells, and the addition of TGF‐β1 would reverse this effect.

Our research indicates that miR‐425‐3p is poorly expressed in myocardial tissues of mice with viral myocarditis. Overexpressed miR‐425‐3p inhibits cardiomyocyte apoptosis and myocardial inflammation in mice with viral myocarditis as well as improves their survival rates through suppressing the TGF‐β1/smad axis.

• TGF-β1
• cardiomyocyte apoptosis
• microRNA-425-3p
• myocardial inflammation
• viral myocarditis

Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies worldwide, with high morbidity, relapse, metastasis and mortality rates. Although liver surgical resection, transplantation, chemotherapy, radiotherapy and some molecular targeted therapeutics may prolong the survival of HCC patients to a certain degree, the curative effect is still poor, primarily because of tumor recurrence and the drug resistance of HCC cells. Liver cancer stem cells (LCSCs), also known as liver tumor-initiating cells, represent one small subset of cancer cells that are responsible for disease recurrence, drug resistance and death. Therefore, understanding the regulatory mechanism of LCSCs in HCC is of vital importance. Thus, new studies that present gene regulation strategies to control LCSC differentiation and replication are under development. In this review, we provide an update on the latest advances in experimental studies on non-coding RNAs (ncRNAs), oncogenes and oncoproteins. All the articles addressed the crosstalk between different ncRNAs, oncogenes and oncoproteins, as well as their upstream and downstream products targeting LCSCs. In this review, we summarize three pathways, the Wnt/β-catenin signaling pathway, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway, and interleukin 6/Janus kinase 2/signal transducer and activator of transcription 3 (IL6/JAK2/STAT3) signaling pathway, and their targeting gene, c-Myc. Furthermore, we conclude that octamer 4 (OCT4) and Nanog are two important functional genes that play a pivotal role in LCSC regulation and HCC prognosis.

• hepatocellular carcinoma
• liver cancer stem cells
• non-coding RNAs
• oncogenes
• oncoproteins

• HCC
• hsa-miR-30d
• miRNA
• predictive biomarker
• regorafenib
• sorafenib

• drug resistance
• hepatocellular carcinoma
• molecular carcinogenesis

Monitoring the early treatment effect of sorafenib in advanced hepatocellular carcinoma (HCC) patients is a diagnostic challenge. In a previous study, we reported the potential role of liver computed tomography perfusion (CTP) in the assessment of the response to sorafenib therapy in HCC. The present study aims to investigate whether sorafenib-targeted genes is correlated with CTP parameter, and investigate the potential of sorafenib-targeted genes in early prediction of therapeutic response to sorafenib in advanced HCC.

A total of 21 HCC patients were enrolled. Sorafenib was administered orally at a dose of 400 mg twice daily continuously. Treatment response was assessed using modified response evaluation criteria in solid tumors (mRECIST) criteria. CTP scanning was performed before and after two weeks of sorafenib treatment using a 320-detector row CT scanner. The perfusion parameters of portal vein flow (PVF), hepatic artery flow (HAF), and perfusion index (PI) were acquired by CTP. The expression levels of several sorafenib-targeted genes were assayed using real-time quantitative PCR and western blot analysis. Logistic regression was performed to analyze the relationship between HAF values and RAF1 expression levels.

According to mRECIST, the disease control rate (CR+PR+SD) of treatment group was 70.5% after two months of treatment. Compared to background controls, tumor tissues exhibited higher HAF. A sorafenib-targeted gene, RAF1 expression, was increased in tumor tissues especially in the sorafenib-resistant group. The sorafenib-resistant group exhibited a significantly higher RAF1 expression and HAF than the sensitive group. Moreover, the RAF1 expression is positively correlated with the HAF value.

RAF1 expression might predict therapeutic effects of sorafenib in advanced HCC, where RAF1 could potentially serve as a molecular marker for monitoring early therapeutic effects after sorafenib treatment.

• Hepatocellular carcinoma
• Liver computed tomography perfusion
• Sorafenib

miR-191 and miR-425 have been proved to be highly expressed in gastric carcinoma (GC). However, little research has been done on their clinical value in serum of patients with advanced GC. In addition, it is not clear whether they can be used as markers for the response and prognosis of GC patients treated with oxaliplatin combined with 5-fluorouracil and FOLFOX chemotherapy.

A total of 230 patients with advanced GC admitted to our hospital were selected as the study objects, all of whom received FOLFOX chemotherapy regimen. Another 100 cases of healthy subjects were included. QRT-PCR was employed to detect the serum expression of miR-191 and miR-425 in patients.

Compared with the healthy subjects, the serum expressions of miR-191 and miR-425 in GC patients were significantly upregulated, which were correlated with differentiation degree and TNM staging, respectively. According to the ROC curve, the AUC of miR-191 and miR-425 for GC diagnosis was 0.937 and 0.901, respectively, while the AUC for differentiation degree diagnosis was 0.854 and 0.822, and that for TNM staging diagnosis was 0.860 and 0.829, respectively. The predictive AUC of miR-191 and miR-425 for chemosensitivity was 0.868 and 0.835, respectively, with a combined predictive AUC of 0.935. Low differentiation degree, high TNM staging, high miR-191 and high miR-425 expressions were independent risk factors for chemotherapy insensitivity. Differentiation degree, TNM staging, chemotherapy effect, miR-191 and miR-425 were independent influencing factors for the prognosis of GC patients.

Up-regulated expression of miR-191 and miR-425 in the serum of patients with advanced GC are effective biomarkers for the diagnosis, chemotherapy and prognosis evaluation of GC.

• FOLFOX
• GC
• chemotherapy
• miR-191
• miR-425
• prognosis

• MACC1-AS1
• PAX8
• hepatocellular carcinoma
• lncRNAs

• Biomarkers, Tumor
• Carcinoma, Hepatocellular/genetics
• Cell Cycle/genetics
• Cell Line, Tumor
• Cell Movement/genetics
• Ectopic Gene Expression
• Epithelial-Mesenchymal Transition/genetics
• Gene Expression Regulation, Neoplastic
• Humans
• Liver Neoplasms/genetics
• PAX8 Transcription Factor/genetics
• RNA Interference
• RNA, Antisense/genetics
• RNA, Long Noncoding/genetics
• Trans-Activators/genetics

• Biomarkers
• Hepatocellular Carcinoma
• Immune checkpoints inhibitors
• Liquid biopsy
• Radiomics
• Sorafenib
• α-fetoprotein

• Biomarkers
• HCC
• MicroRNA
• diagnosis
• hepatocellular carcinoma
• management
• prognosis
• treatment.

• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/genetics
• Carcinogenesis/genetics
• Carcinoma, Hepatocellular/diagnosis
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/therapy
• Genetic Markers/genetics
• Humans
• Liver Neoplasms/diagnosis
• Liver Neoplasms/genetics
• Liver Neoplasms/therapy
• MicroRNAs/genetics
• Prognosis

Sorafenib is an oral kinase inhibitor that enhances survival in patients affected by advanced hepatocellular carcinoma (HCC). According to the results of two registrative trials, this drug represents a gold quality standard in the first line treatment of advanced HCC. Recently, lenvatinib showed similar results in terms of survival in a non-inferiority randomized trial study considering the same subset of patients. Unlike other targeted therapies, predictive and prognostic markers in HCC patients treated with sorafenib are lacking. Their identification could help clinicians in the daily management of these patients, mostly in light of the new therapeutic options available in the first.

• Sorafenib
• hepatocellular carcinoma
• predictive factors
• prognostic factors

• Animals
• Antineoplastic Agents/adverse effects
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/analysis
• Carcinoma, Hepatocellular/drug therapy
• Humans
• Liver Neoplasms/drug therapy
• Phenylurea Compounds/therapeutic use
• Prognosis
• Protein Kinase Inhibitors/adverse effects
• Protein Kinase Inhibitors/therapeutic use
• Quinolines/therapeutic use
• Sorafenib/adverse effects
• Sorafenib/therapeutic use

Exosomes are important mediators of intercellular communication. Previously, we characterized circulating exosomal miR-425-3p as a non-invasive prognostic marker for predicting clinical response to platinum-based chemotherapy in patients with non-small cell lung cancer (NSCLC).

Circulating exosomal miR-425-3p was validated by qRT-PCR in paired serum samples from NSCLC patients during the course of platinum-based chemotherapy. Cell coculture was performed to examine the effects of exosomal miR-425-3p on the sensitivity of recipient A549 cells to cisplatin. Using bioinformatics, ChIP and luciferase reporter assays, the transcription factor essential for miR-425-3p expression was identified. Autophagic activity in the recipient cells was determined by Western blot and fluorescence microscopy.

Higher levels of exosomal miR-425-3p were found in serum samples from the patients in tolerance versus those at baseline. An upward trend in the expression of circulating exosomal miR-425-3p was revealed during chemotherapy. Furthermore, the expression of exosomal miR-425-3p could be induced by cisplatin in NSCLC cells. Exosomes isolated from either cisplatin-treated or cisplatin-resistant NSCLC cells conferred chemoresistance to sensitive A549 cells in a miR-425-3p-dependent manner. Cisplatin-induced c-Myc was found to directly bind the miR-425-3p promoter and transactivated its expression. Exosomal miR-425-3p facilitated autophagic activation in the recipient cells by targeting AKT1, eventually leading to chemoresistance.

Our results suggest that apart from a prognostic marker of treatment response, exosomal miR-425-3p might be a potential dynamic biomarker to tailor cisplatin resistance in NSCLC patients during the treatment and represent a promising therapeutic target for therapy-resistant NSCLC.

• NSCLC
• autophagy
• chemoresistance
• exosomes
• miR-425-3p
• platinum-based chemotherapy

• chemoresistance
• immune checkpoint
• long noncoding RNAs
• microRNAs
• targeted therapy

• HBV
• HCV
• exosome
• hepatocellular carcinoma
• microRNA
• therapy

OncoHepa test is a multigene expression profile test developed for assessment of hepatocellular carcinoma (HCC) prognosis. Multiplication of α-FP, des-γ-carboxy prothrombin (DCP) and tumor volume (TV) gives the α-FP-DCP-volume (ADV) score, which is also developed for assessment of HCC prognosis.

The predictive powers of OncoHepa test and ADV score were validated in 35 patients who underwent curative hepatic resection for naïve solitary HCCs ≤5 cm.

Median tumor diameter was 3.0 cm. Tumor recurrence and patient survival rates were 28.6% and 100% at 1 year, 48.6% and 82.9% at 3 years, and 54.3% and 71.4% at 5 years, respectively. The site of first tumor recurrence was the remnant liver in 18, lung in 1, and the peritoneum in 1. All patients with HCC recurrence received locoregional treatment. OncoHepa test showed marginal prognostic significance for tumor recurrence and patient survival. ADV score at 4log also showed marginal prognostic difference with respect to tumor recurrence and patient survival. Combination of these 2 tests resulted in greater prognostic significance for both tumor recurrence (P = 0.046) and patient survival (P = 0.048).

Both OncoHepa test and ADV score have considerably strong prognostic power, thus individual and combined findings of OncoHepa test and ADV score will be helpful to guide postresection surveillance in patients with solitary HCCs ≤5 cm.

• Genes
• Prognosis
• Recurrence
• Survival

Sorafenib has been considered the standard of care for patients with advanced unresectable hepatocellular carcinoma (HCC) since 2007 and numerous studies have investigated the role of markers involved in the angiogenesis process at both the expression and genetic level and clinical aspect. What results have ten years of research produced? Several clinical and biological markers are associated with prognosis. The most interesting clinical parameters are adverse events, Barcelona Clinic Liver Cancer stage, and macroscopic vascular invasion, while several single nucleotide polymorphisms and plasma angiopoietin-2 levels represent the most promising biological biomarkers. A recent pooled analysis of two phase III randomized trials showed that the neutrophil-to-lymphocyte ratio, etiology and extra-hepatic spread are predictive factors of response to sorafenib, but did not identify any predictive biological markers. After 10 years of research into sorafenib there are still no validated prognostic or predictive factors of response to the drug in HCC. The aim of the present review was to summarize 10 years of research into sorafenib, looking in particular at the potential of associated clinical and biological markers to predict its efficacy in patients with advanced HCC.

• Biomarker
• Angiopoietin
• Neutrophil-to-lymphocyte ratio
• Polymorphisms
• Sorafenib
• MicroRNA
• Adverse events
• Hepatocellular carcinoma
• Vascular endothelial growth factor

• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Carcinoma, Hepatocellular/blood
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/pathology
• Clinical Trials, Phase III as Topic
• Drug Resistance, Neoplasm/genetics
• Humans
• Leukocyte Count
• Liver/blood supply
• Liver/pathology
• Liver Neoplasms/blood
• Liver Neoplasms/drug therapy
• Liver Neoplasms/genetics
• Liver Neoplasms/pathology
• Neoplasm Invasiveness/pathology
• Neoplasm Invasiveness/prevention & control
• Prognosis
• Sorafenib/pharmacology
• Sorafenib/therapeutic use
• Treatment Outcome

• Anilides/therapeutic use
• Antibodies, Monoclonal/therapeutic use
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents/therapeutic use
• Carcinoma, Hepatocellular/drug therapy
• Carcinoma, Hepatocellular/pathology
• Humans
• Immunotherapy/methods
• Liver Neoplasms/drug therapy
• Liver Neoplasms/pathology
• Nivolumab/therapeutic use
• Phenylurea Compounds/therapeutic use
• Protein Kinase Inhibitors/therapeutic use
• Pyridines/therapeutic use
• Quinolines/therapeutic use
• Sorafenib/therapeutic use
• Ramucirumab

An increasing number of studies have demonstrated the function of microRNAs (miRNAs) in the initiation and development of various types of cancer. Among them, miR-425-5p is proven to serve an important function in several types of cancer, including gastric, cervical cancer, and hepatocellular carcinoma. However, the function of miR-425-5p in renal cell carcinoma (RCC) remains unclear. In the present study, it was demonstrated that the expression level of miR-425-5p was upregulated in RCC tissues and cell lines compared with normal tissues and cell lines (P<0.05). Additionally, Cell Counting kit-8 and MTT assays were employed to assess cell viability and proliferation, whereas wound healing and Transwell assays were employed to examine migration and invasion. The results demonstrated that upregulation of miR-425-5p promoted cell viability and the invasion and migration of ACHN and 786O cells (P<0.05). Flow cytometric analysis confirmed that upregulation of miR-425-5p inhibited apoptosis of ACHN and 786O cells (P<0.05). Downregulation of miR-425-5p inhibited the viability and invasion and migration of ACHN and 786O cells (P<0.05). In the present study, upregulation of miR-425-5p inhibited apoptosis of ACHN and 786O cells whereas no differences in early apoptotic rate were observed between the inhibitor and inhibitor NC groups for 786O and ACHN cells. These results indicate that miR-425-5p may act as an oncogene in RCC.

• microRNA
• microRNA-425-5p
• oncogene
• renal cell carcinoma

• C19MC miRNAs
• CT antigens
• HCC
• Side Population

• PTEN
• SCAI
• hepatocellular carcinoma
• integrin β1
• miR-425-5p

• NOTCH1
• NSCLC
• miR-494-3p
• miRNA
• stem cells

Angiogenesis is essential for tumor growth and metastasis. Understanding the regulation of tumor angiogenesis has become increasingly important. MicroRNAs (miRNAs) are small noncoding RNAs that function in diverse biological processes via post-transcriptional regulation. Extensive studies have revealed two important regulatory roles of miRNAs in tumor angiogenesis: miRNAs in tumor cells affect the activity of endothelial cells via non-cell-autonomous mechanisms, and miRNAs in endothelial cells regulate the cell-autonomous behavior. Recent advances have further highlighted the role of tumor-derived extracellular vesicles in the regulation of tumor angiogenesis via transferring miRNAs to endothelial cells. In this review, we summarize the regulatory role of miRNA in tumor angiogenesis, with a highlight on clinical implications of miRNAs as biomarkers for anti-angiogenic therapy response, and as therapeutic interventions against tumor angiogenesis in vivo.

• Biomarker
• Extracellular vesicle
• Tumor angiogenesis
• miRNA delivery
• microRNA

• Biomarkers
• Diagnosis
• IgA nephropathy
• Microarray
• microRNA

• Gene expression omnibus
• Gene ontology
• Hepatocellular carcinoma
• Network analysis
• miRNA-34a

• hepatocellular carcinoma
• microRNAs
• resistance
• sorafenib

• Drug resistance
• Liver cancer
• Molecular targeted therapy
• Sorafenib

Numerous articles reported that dysregulated expression levels of miRNAs correlated with survival time of HCC patients. However, there has not been a comprehensive meta-analysis to evaluate the accurate prognostic value of miRNAs in HCC.

Meta-analysis.

Studies, published in English, estimating expression levels of miRNAs with any survival curves in HCC were identified up until 15 April, 2017 by performing online searches in PubMed, EMBASE, Web of Science and Cochrane Database of Systematic Reviews by two independent authors. The pooled hazard ratios (HR) with 95% confidence intervals (CI) were used to estimate the correlation between miRNA expression and overall survival (OS).

54 relevant articles about 16 miRNAs, with 6464 patients, were ultimately included. HCC patients with high expression of tissue miR-9 (HR = 2.35, 95% CI = 1.46–3.76), miR-21 (HR = 1.76, 95% CI = 1.29–2.41), miR-34c (HR = 1.64, 95% CI = 1.05–2.57), miR-155 (HR = 2.84, 95% CI = 1.46–5.51), miR-221 (HR = 1.76, 95% CI = 1.02–3.04) or low expression of tissue miR-22 (HR = 2.29, 95% CI = 1.63–3.21), miR-29c (HR = 1.35, 95% CI = 1.10–1.65), miR-34a (HR = 1.84, 95% CI = 1.30–2.59), miR-199a (HR = 2.78, 95% CI = 1.89–4.08), miR-200a (HR = 2.64, 95% CI = 1.86–3.77), miR-203 (HR = 2.20, 95% CI = 1.61–3.00) have significantly poor OS (P < 0.05). Likewise, HCC patients with high expression of blood miR-21 (HR = 1.73, 95% CI = 1.07–2.80), miR-192 (HR = 2.42, 95% CI = 1.15–5.10), miR-224 (HR = 1.56, 95% CI = 1.14–2.12) or low expression of blood miR-148a (HR = 2.26, 95% CI = 1.11–4.59) have significantly short OS (P < 0.05).

In conclusion, tissue miR-9, miR-21, miR-22, miR-29c, miR-34a, miR-34c, miR-155, miR-199a, miR-200a, miR-203, miR-221 and blood miR-21, miR-148a, miR-192, miR-224 demonstrate significantly prognostic value. Among them, tissue miR-9, miR-22, miR-155, miR-199a, miR-200a, miR-203 and blood miR-148a, miR-192 are potential prognostic candidates for predicting OS in HCC.

• hepatocellular carcinoma
• meta-analysis
• microRNA
• prognosis

• Antineoplastic Agents/pharmacology
• Carcinoma, Hepatocellular/genetics
• Carcinoma, Hepatocellular/metabolism
• Cell Line, Tumor
• Cell Survival/genetics
• Drug Resistance, Neoplasm/genetics
• Gene Expression Regulation, Neoplastic
• Genes, erbB-1
• Humans
• Interleukin-6/metabolism
• Liver Neoplasms/genetics
• Liver Neoplasms/metabolism
• MicroRNAs/genetics
• Multigene Family
• Pharmacogenetics
• Signal Transduction
• Sorafenib/pharmacology