Combinatorial protection of cochlear hair cells: not too little but not too much.

Background: A number of drugs are toxic to the cochlear sensory cells known as hair cells (HCs), resulting in hearing loss. Treatment with survival-promoting growth factors, antioxidants, and inhibitors of cell death pathways or proteinases have been shown to reduce HC damage in in vivo and/or in vitro animal models. Conversely, translation to humans has often been disappointing. This may be due to the complexity of intracellular damage processes. We hypothesized that combining treatments targeting different cellular processes would be more effective. Methods: Using an in vitro model of gentamicin ototoxicity for murine cochlear hair cells, we screened all 56 possible combinations of inhibitors targeting five different cell damage mechanisms, plus the activator of one cell survival pathway, each of which have been shown to be singly effective in preventing HC loss in experimental studies. A high dose of gentamicin (200 µM) was used over three days in culture. All compounds were added at a dosage below that required for significant protection in the assay, and only this single dose was then employed. This was done so that we could more easily detect interactive, as opposed to additive, effects. Results: Increasing protection of hair cells was observed as combinations of compounds were increased from two to four factors, although not all combinations were equally protective. The optimal combination of four compounds consisted of an anti-oxidant, an apoptosis inhibitor, an autophagy inhibitor and a protective growth factor. Increasing the number of factors to five or six resulted in decreased protection. Conclusion: The results support the hypothesis that targeting multiple cellular damage or survival pathways provides more an effective hair cell protection approach. The results help to identify critical interactions among the cellular processes that operate in gentamicin ototoxicity. They also suggest that inhibiting too many biological processes impairs functions critical to HC survival, resulting in decreased protection.

A Review of Current Approaches to Pain Management in Knee Osteoarthritis with a Focus on Italian Clinical Landscape.

The global cases of knee osteoarthritis (KOA) are projected to increase by 74.9% by 2050. Currently, over half of patients remain dissatisfied with their pain relief. This review addresses unmet needs for moderate-to-severe KOA pain; it offers evidence and insights for improved management. Italian experts from the fields of rheumatology, physical medicine and rehabilitation, orthopedics, primary care, and pain therapy have identified several key issues. They emphasized the need for standardized care protocols to address inconsistencies in patient management across different specialties. Early diagnosis is crucial, as cartilage responds better to early protective and structural therapies. Faster access to physiatrist evaluation and reimbursement for physical, rehabilitative, and pharmacological treatments, including intra-articular (IA) therapy, could reduce access disparities. Concerns surround the adverse effects of oral pharmacological treatments, highlighting the need for safer alternatives. Patient satisfaction with corticosteroids and hyaluronic acid-based IA therapies reduces over time and there is no consensus on the optimal IA therapy protocol. Surgery should be reserved for severe symptoms and radiographic KOA evidence, as chronic pain post-surgery poses significant societal and economic burdens. The experts advocate for a multidisciplinary approach, promoting interaction and collaboration between specialists and general practitioners, to enhance KOA care and treatment consistency in Italy.

Pure large-cell neuroendocrine carcinoma of the ovary with a somatic BRCA1 mutation: The first reported case and the review of the literature.

Pure large-cell neuroendocrine carcinomas of the ovary are extremely rare, so there is a lack of molecular information on this type of cancer. Herein, we presented a pure primary large-cell neuroendocrine carcinomas of the ovary in a 72-year-old female with a pathogenic somatic mutation at the c.5332+1g>a splice site of the BRCA1 gene and with no TP53 mutation. She was uneventful 32 months after the operation and chemotherapies. To the best of our knowledge, this is the first report of a BRCA1 somatic mutation in the ovary large-cell neuroendocrine carcinomas. Testing BRCA1/2 mutations in patients with large ovarian cell neuroendocrine carcinomas might provide an opportunity for their future target treatments. It would expand our understanding.

Small Molecule-Drug Conjugates Emerge as a New Promising Approach for Cancer Treatment.

Antibody drug conjugates (ADCs) have emerged as a new promising class of anti- cancer agents. However, limitations such as higher costs and unavoidable immunogenicity due to their relatively large structures cannot be ignored. Therefore, the development of lightweight drugs such as small molecule-drug conjugates (SMDCs) based on the ADC design idea has become a new option for targeted therapy. SMDCs are derived from the coupling of small-molecule targeting ligands with cytotoxic drugs. They are composed of three parts: small-molecule targeting ligands, cytotoxic molecules, and linkers. Compared with ADCs, SMDCs can be more rapidly and evenly dispersed into tumor tissues, with low cost and no immunogenicity. In this article, we will give a comprehensive review of different types of SMDCs currently under clinical trials to provide ideas and inspirations for the development of clinically applicable SMDCs.

Anti-angiogenic and antitumor effects of anlotinib combined with bevacizumab for colorectal cancer.

BACKGROUND: The progression and metastasis of tumors are typically accompanied by angiogenesis. Crucially, vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) play a significant role in tumor-associated angiogenesis. In this study, the aim was to investigate the antitumor effect of combining bevacizumab (Bev) with anlotinib (An) on colorectal cancer (CRC). METHODS: The CCK-8 assay, EdU assay, and Annexin V staining were conducted to evaluate the proliferation and apoptosis of CRC cells in vitro. The migration capability of CRC cells and HUVECs was assessed using the Transwell assay. Additionally, the tube formation capability of HUVECs was investigated. Furthermore, the antitumor and antiangiogenic effects were evaluated in the BALB/c mice model using immunohistochemistry, TUNEL staining, and 18F-FDG PET/CT imaging. Finally, we analyzed the inhibitory effect of Bev and/or An on related signaling effectors through western blotting. RESULTS: The in vivo CRC mice model revealed that the combination of Bev + An significantly suppressed tumor formation and angiogenesis. Bev + An inhibited tumor glucose metabolism and increased the median survival period in tumor-bearing mice. Mechanistically, the expressions of VEGF, VEGFR2, PDGFR, and FGFR, as well as the phosphorylation levels of AKT, were inhibited after Bev+An treatment. In conclusion, the dual vertical targeting of VEGF and VEGFR in the CRC mice model strongly inhibited tumor growth and angiogenesis, with the suppression of the AKT signaling pathway playing a partial role.

The role of mitochondrial dynamics in disease.

Mitochondria are multifaceted and dynamic organelles regulating various important cellular processes from signal transduction to determining cell fate. As dynamic properties of mitochondria, fusion and fission accompanied with mitophagy, undergo constant changes in number and morphology to sustain mitochondrial homeostasis in response to cell context changes. Thus, the dysregulation of mitochondrial dynamics and mitophagy is unsurprisingly related with various diseases, but the unclear underlying mechanism hinders their clinical application. In this review, we summarize the recent developments in the molecular mechanism of mitochondrial dynamics and mitophagy, particularly the different roles of key components in mitochondrial dynamics in different context. We also summarize the roles of mitochondrial dynamics and target treatment in diseases related to the cardiovascular system, nervous system, respiratory system, and tumor cell metabolism demanding high-energy. In these diseases, it is common that excessive mitochondrial fission is dominant and accompanied by impaired fusion and mitophagy. But there have been many conflicting findings about them recently, which are specifically highlighted in this view. We look forward that these findings will help broaden our understanding of the roles of the mitochondrial dynamics in diseases and will be beneficial to the discovery of novel selective therapeutic targets.

Functions and mechanisms of protein lysine butyrylation (Kbu): Therapeutic implications in human diseases.

Post-translational modifications (PTM) are covalent modifications of proteins or peptides caused by proteolytic cleavage or the attachment of moieties to one or more amino acids. PTMs play essential roles in biological function and regulation and have been linked with several diseases. Modifications of protein acylation (Kac), a type of PTM, are known to induce epigenetic regulatory processes that promote various diseases. Thus, an increasing number of studies focusing on acylation modifications are being undertaken. Butyrylation (Kbu) is a new acylation process found in animals and plants. Kbu has been recently linked to the onset and progression of several diseases, such as cancer, cardiovascular diseases, diabetes, and vascular dementia. Moreover, the mode of action of certain drugs used in the treatment of lymphoma and colon cancer is based on the regulation of butyrylation levels, suggesting that butyrylation may play a therapeutic role in these diseases. In addition, butyrylation is also commonly involved in rice gene expression and thus plays an important role in the growth, development, and metabolism of rice. The tools and analytical methods that could be utilized for the prediction and detection of lysine butyrylation have also been investigated. This study reviews the potential role of histone Kbu, as well as the mechanisms underlying this process. It also summarizes various enzymes and analytical methods associated with Kbu, with the goal of providing new insights into the role of Kbu in gene regulation and diseases.

Ketogenic dietary therapies in epilepsy: recommendations of the Italian League against Epilepsy Dietary Therapy Study Group.

A stepwise increase in the utilization of ketogenic dietary therapies for drug-resistant epilepsy has been observed in Italy in the last decade, although it is still considered often underused in many centers when compared to other countries. The Dietary Therapy Study Group of the Italian League against Epilepsy proposes practical recommendations to improve shared knowledge and facilitate the application of ketogenic dietary therapies, optimizing its efficacy and tolerability. The experts involved (11 child neuropsychiatrists, two adult neurologists, one psychologist, one pharmacologist, one pediatric endocrinologist, one representative of patients' associations, and three dietitians and clinical nutritionists) responded to a survey on current clinical practice issues and were asked to discuss controversial topics related to supplementation, long-term maintenance, transition, and a multidisciplinary approach to ketogenic dietary therapies. Practical indications for patient selection, diet initiation, management, side effects prevention, and follow-up are provided.

SIRT1 mediated gastric cancer progression under glucose deprivation through the FoxO1-Rab7-autophagy axis.

Purpose: Silent mating type information regulator 2 homolog 1 (SIRT1) and autophagy have a two-way action (promoting cell death or survival) on the progression and treatment of gastric cancer (GC) under different conditions or environments. This study aimed to investigate the effects and underlying mechanism of SIRT1 on autophagy and the malignant biological behavior of GC cells under conditions of glucose deprivation (GD). Materials and methods: Human immortalized gastric mucosal cell GES-1 and GC cell lines SGC-7901, BGC-823, MKN-45 and MKN-28 were utilized. A sugar-free or low-sugar (glucose concentration, 2.5 mmol/L) DMEM medium was used to simulate GD. Additionally, CCK8, colony formation, scratches, transwell, siRNA interference, mRFP-GFP-LC3 adenovirus infection, flow cytometry and western blot assays were performed to investigate the role of SIRT1 in autophagy and malignant biological behaviors (proliferation, migration, invasion, apoptosis and cell cycle) of GC under GD and the underlying mechanism. Results: SGC-7901 cells had the longest tolerance time to GD culture conditions, which had the highest expression of SIRT1 protein and the level of basal autophagy. With the extension of GD time, the autophagy activity in SGC-7901 cells also increased. Under GD conditions, we found a close relationship between SIRT1, FoxO1 and Rab7 in SGC-7901 cells. SIRT1 regulated the activity of FoxO1 and upregulated the expression of Rab7 through deacetylation, which ultimately affected autophagy in GC cells. In addition, changing the expression of FoxO1 provided feedback on the expression of SIRT1 in the cell. Reducing SIRT1, FoxO1 or Rab7 expression significantly inhibited the autophagy levels of GC cells under GD conditions, decreased the tolerance of GC cells to GD, enhanced the inhibition of GD in GC cell proliferation, migration and invasion and increased apoptosis induced by GD. Conclusion: The SIRT1-FoxO1-Rab7 pathway is crucial for the autophagy and malignant biological behaviors of GC cells under GD conditions, which could be a new target for the treatment of GC.

Current insight on the mechanisms of programmed cell death in sepsis-induced myocardial dysfunction.

Sepsis is a clinical syndrome characterized by a dysregulated host response to infection, leading to life-threatening organ dysfunction. It is a high-fatality condition associated with a complex interplay of immune and inflammatory responses that can cause severe harm to vital organs. Sepsis-induced myocardial injury (SIMI), as a severe complication of sepsis, significantly affects the prognosis of septic patients and shortens their survival time. For the sake of better administrating hospitalized patients with sepsis, it is necessary to understand the specific mechanisms of SIMI. To date, multiple studies have shown that programmed cell death (PCD) may play an essential role in myocardial injury in sepsis, offering new strategies and insights for the therapeutic aspects of SIMI. This review aims to elucidate the role of cardiomyocyte's programmed death in the pathophysiological mechanisms of SIMI, with a particular focus on the classical pathways, key molecules, and signaling transduction of PCD. It will explore the role of the cross-interaction between different patterns of PCD in SIMI, providing a new theoretical basis for multi-target treatments for SIMI.

Vulvar Malignant Melanoma: A Narrative Review.

Malignant melanoma is a fatal disease that affects all skin sites. Among these, vulvar melanoma (VM) is a rare gynecological condition that accounts for 5% of all vulvar neoplasms. VM primarily affects older Caucasian women and its relationship to sun exposure is undefined. Diagnosis is defined by biopsy but many clinical, dermatoscopic, and confocal microscopic features can guide doctors. The molecular profile is characterized by the KIT mutation, revealed by all of the technologies that are used (classical sequencing, next-generation sequencing, and immunohistochemical staining). BRAF and NRAS mutations are also common in VM. All of these mutations are possible therapeutic targets. Today, surgery remains the first treatment choice for primary VM. The role of neoadjuvant and adjuvant therapy is scarce and the treatment of relapses is widely debated.

Role of the hedgehog signaling pathway in rheumatic diseases: An overview.

Hedgehog (Hh) signaling pathway is an evolutionarily conserved signal transduction pathway that plays an important regulatory role during embryonic development, cell proliferation, and differentiation of vertebrates, and it is often inhibited in adult tissues. Recent evidence has shown that Hh signaling also plays a key role in rheumatic diseases, as alterations in their number or function have been identified in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic sclerosis, and Sjogren's Syndrome. As a result, emerging studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of Hh signaling in rheumatic diseases.

Age-related macular degeneration: Epidemiology, genetics, pathophysiology, diagnosis, and targeted therapy.

Age-related macular degeneration (AMD) is a complex eye disorder and is the leading cause of incurable blindness worldwide in the elderly. Clinically, AMD initially affects the central area of retina known as the macula and it is classified as early stage to late stage (advanced AMD). The advanced AMD is classified into the nonexudative or atrophic form (dry AMD) and the exudative or neovascular form (wet AMD). More severe vision loss is typically associated with the wet form. Multiple genetic factors, lipid metabolism, oxidative stress and aging, play a role in the etiology of AMD. Dysregulation in genetic to AMD is established to 46%-71% of disease contribution, with CFH and ARMS2/HTRA1 to be the two most notable risk loci among the 103 identified AMD associated loci so far. Chronic cigarette smoking is the most proven consistently risk living habits for AMD. Deep learning algorithm has been developed based on image recognition to distinguish wet AMD and normal macula with high accuracy. Currently, anti-vascular endothelial growth factor (VEGF) therapy is highly effective at treating wet AMD. Several new generation AMD drugs and iPSC-derived RPE cell therapy are in the clinical trial stage and are promising to improve AMD treatment in the near future.

PSMC2 knockdown inhibits the progression of oral squamous cell carcinoma by promoting apoptosis via PI3K/Akt pathway.

Proteasome 26S subunit, ATPase 2 (PSMC2) is a recently identified gene which is potentially associated with human carcinogenesis. However, the effects of PSMC2 on oral squamous cell carcinoma (OSCC) is still unclear. Here, we investigated PSMC2 expression in OSCC tissues and explored its effects on the biological behaviors of OSCC cells. PSMC2 expression was evaluated by immunohistochemistry in a tissue microarray containing 60 OSCC tissues and 9 normal tissues. PSMC2 was knocked down through lentivirus infection in OSCC cell lines. MTT, colony formation, flow cytometry, transwell, and scratch assays were performed to detect effects of PSMC2 knockdown on phenotypes of OSCC cells. Human apoptosis antibody array was used to screen potential downstream of PSMC2 in OSCC. Finally, the effects of PSMC2 knockdown on tumor growth were assessed in a tumor xenograft model using BALB/c nude mice. PSMC2 expression was significantly upregulated in OSCC tissues compared with normal tissues and correlated with poor prognosis. PSMC2 knockdown significantly suppressed cell proliferation, migration, but promoted apoptosis of OSCC cells. Additionally, we confirmed that PSMC2 knockdown can increase the expression of pro-apoptotic proteins. Furthermore, we found that PSMC2 knockdown downregulated expression of p100, p-Akt, CDK6, and upregulated of MAPK9. Xenograft experiments revealed that PSMC2 knockdown can suppress OSCC tumor growth and promote apoptosis. This study demonstrated that PSMC2 plays a critical role in OSCC progression through affecting pro-apoptotic protein expression and apoptosis pathways. It indicated that targeting PSMC2 might be a promising strategy for OSCC treatment.

The Application Progress of Patient-Derived Tumor Xenograft Models After Cholangiocarcinoma Surgeries.

Surgical treatment is the only possible cure for cholangiocarcinoma (CCA) at present. However, the high recurrence rate of postoperative CCA leads to a very poor prognosis for patients, effective postoperative chemotherapy is hence the key to preventing the recurrence of CCA. The sensitivity of CCA to cytotoxic chemotherapy drugs and targeted drugs varies from person to person, and therefore, the screening of sensitive drugs has become an important topic after CCA surgeries. Patient-Derived tumor Xenograft models (PDX) can stably retain the genetic and pathological characteristics of primary tumors, and better simulate the tumor microenvironment of CCA. The model is also of great significance in screening therapeutic targeted drugs after CCA, analyzing predictive biomarkers, and improving signal pathways in prognosis and basic research. This paper will review the current established methods and applications of the patient-derived tumor xenograft model of cholangiocarcinoma, aiming to provide new ideas for basic research and individualized treatment of cholangiocarcinoma after surgery.

Response to the combination use of pazopanib with olaratumab in a patient with lung-metastatic embryonal rhabdomyosarcoma: a case report.

Embryonal rhabdomyosarcoma (ERMS) is associated with a low prevalence, poor prognosis, and limited treatment efficacy. Here, we report a case of a 21-year-old male whose disease relapsed in the thoracic cavity following traditional chemotherapy. The patient received eight sequential cycles of traditional chemotherapy using a combination of the cyclophosphamide + vincristine + doxorubicin hydrochloride liposome (CAV) and etoposide + ifosfamide (IE) regimens. The therapeutic effect of the combination regimen had been worked in short times. After a month, ERMS had relapsed in the whole lung after traditional chemotherapy. The treatment method was changed immediately and the patient received targeted therapy with a combination of pazopanib and olaratumab. The therapeutic effect of the combination regimen was evaluated for a complete response (CR). After two months, CT imaging revealed that most of the metastatic lesions in the lung had disappeared. This is the first case to report the use of pazopanib and olaratumab in relapsed ERMS with a curative effect resulting in a CR. Pazopanib is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Thus, combining pazopanib with targeted therapy may play an important role and provide a reference for the treatment of relapsed ERMS.

RNA sequencing reveals BMP4 as a basis for the dual-target treatment of diabetic retinopathy.

BACKGROUND: Diabetic retinopathy (DR), currently considered as a neurovascular disease, has become the major cause of blindness. More and more scholars believe that DR is no longer just a kind of microvascular disease, but accompanied by retinal neurodegenerative changes. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs is a classic treatment for DR; however, anti-VEGF drugs can exacerbate fibrosis and eventually lead to retinal detachment. The aim of this study was to explore the pathogenesis of DR and identified new treatments that can provide dual-target intervention for angiogenesis and fibrosis. METHODS: We explored changes in gene expression in high glucose-induced vascular endothelial cells using RNA sequencing (RNA-seq) technology. We identified bone morphogenetic protein 4 (BMP4) and SMAD family member 9 (SMAD9) among 449 differentially expressed genes from RNA-seq data and confirmed the expression of these two genes in the blood of diabetes patients by RT-PCR and in streptozotocin-induced rat retinas by RT-PCR, immunofluorescence, and western blot. Moreover, considering that DR is a multifactorial and multicellular disease, we used hydrogen peroxide (H2O2), advanced glycation end products (AGEs), CoCl2, 4-hydroxynonenal (4-HNE), and hypoxia to induce three human retinal cell types (Müller, retinal pigment epithelium, and human retinal capillary endothelial cells) to simulate the pathogenesis of DR, and MTT experiment, scratch experiment, Transwell experiment, and lumen formation experiment were used to test whether the model was successfully established. Then, we verified the overexpression of these two genes in the cell models by RT-PCR, immunofluorescence, and western blot. We further tested the effects of BMP4 on retinal cells. We use BMP4 to stimulate retinal cells and observe the effect of BMP4 on retinal cells by MTT experiment, scratch experiment, and RT-PCR. RESULTS: The results demonstrated that BMP4 and SMAD9 were highly expressed in both in vivo and in vitro models, while BMP4 could significantly upregulate the expression of SMAD9 and promote the expression of VEGF and fibrosis factors. CONCLUSIONS: This study is the first to analyze the mechanism by which high glucose levels affect retinal vascular endothelial cells through RNA transcriptome sequencing and indicates that BMP4 may be a potential target for the dual-target treatment (anti-VEGF and anti-fibrosis) of DR. KEY MESSAGES: • High-glucose effect on vascular endothelial cell was analyzed by RNA-seq. • KEGG analysis revealed enrichment of TGF-beta signaling pathway. • SMAD9 and BMP4 expression was upregulated in all samples. • Dual-target therapy of PDR by antagonizing BMP4.

Bevacizumab combined with apatinib enhances antitumor and anti-angiogenesis effects in a lung cancer model in vitro and in vivo.

Angiogenesis is involved in the proliferation and metastasis of solid tumours; hence, it is an attractive therapeutic target. However, most patients who undergo anti-angiogenic drug treatment do not achieve complete tumour regression, resulting in drug resistance. The objective of this research is to explore the therapeutic effect of combining bevacizumab (Bev), an anti-vascular endothelial growth factor (VEGF)-A antibody, with apatinib (Apa), a VEGR receptor (VEGFR)-2-targeting tyrosine kinase inhibitor, in non-small cell lung cancer (NSCLC). In vitro, we assessed the influence which Bev + Apa treatment exerts upon the proliferation as well as apoptosis of Lewis lung carcinoma (LLC) cells in virtue of the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide as assay as well as Annexin V staining, respectively. For in vivo assessment, we established a tumour-bearing mouse model with LLC cells and investigated the anti-angiogenic and antitumor effects of Bev + Apa by 18F-FDG PET/CT imaging, immunohistochemistry and TUNEL staining. Bev + Apa treatment significantly inhibited LLC cell growth and proliferation in a larger scale compared to therapy of either of the only agent. Bev + Apa inhibited tumour growth and extended the median survival time of tumour-bearing mice. Mechanistically, Bev + Apa reduced angiogenesis by inhibiting VEGF and VEGFR-2 expression and reducing glucose metabolism in tumour tissues. Thus, Bev and Apa inhibited tumour angiogenesis synergistically, indicating their potential clinical utility for NSCLC treatment.

[Hepatocellular carcinoma-derived exosomal miRNA expression and its clinical value].

The early diagnosis and effective treatment of hepatocellular carcinoma (HCC) still remains a difficult problem that plagues the medical community. Exosomes are microvesicles with a diameter of 40~100 nm, and contains proteins, lipids and nucleic acids (mRNAs, lncRNAs, circRNAs, and microRNAs). They serve as an information exchange carrier, and play an important role in regulating and controlling the biomolecular function to maintain the stability of the intracellular environment. The function of exosomes in HCC includes intercellular communication, neoangiogenesis, cancer cell metastasis and multidrug resistance, which mediates the transformation of microRNAs (miRNA) and regulate the microenvironment of tumor progression, and then affect the pathophysiological behavior of cancer cells. Exosome-derived miRNA can be used for HCC monitoring or potential specific markers of early diagnosis. In addition, with the development and application prospects it could be a therapeutic goal for HCC. This paper summarizes the recent progress in the study of HCC-derived exosomal miRNA.

Hepatocellular carcinoma-derived exosomal miRNA expression and its clinical value / 中华肝脏病杂志

The early diagnosis and effective treatment of hepatocellular carcinoma (HCC) still remains a difficult problem that plagues the medical community. Exosomes are microvesicles with a diameter of 40~100 nm, and contains proteins, lipids and nucleic acids (mRNAs, lncRNAs, circRNAs, and microRNAs). They serve as an information exchange carrier, and play an important role in regulating and controlling the biomolecular function to maintain the stability of the intracellular environment. The function of exosomes in HCC includes intercellular communication, neoangiogenesis, cancer cell metastasis and multidrug resistance, which mediates the transformation of microRNAs (miRNA) and regulate the microenvironment of tumor progression, and then affect the pathophysiological behavior of cancer cells. Exosome-derived miRNA can be used for HCC monitoring or potential specific markers of early diagnosis. In addition, with the development and application prospects it could be a therapeutic goal for HCC. This paper summarizes the recent progress in the study of HCC-derived exosomal miRNA.