Research progress on immune-related therapeutic targets of brain injury caused by cerebral ischemia.

Stroke is the second leading cause of death worldwide and a leading cause of disability. The innate immune response occurs immediately after cerebral ischemia, resulting in adaptive immunity. More and more experimental evidence has proved that the immune response caused by cerebral ischemia plays an important role in early brain injury and later the recovery of brain injury. Innate immune cells and adaptive cells promote the occurrence of cerebral ischemic injury but also protect brain cells. A large number of studies have shown that cytokines and immune-related substances also have dual functions of promoting injury, reducing injury, or promoting injury recovery in the later stage of cerebral ischemia. They can be an important target for treating cerebral ischemic recovery. Therefore, this study discussed the immune cells, cytokines, and immune-related substances with dual roles in cerebral ischemia and summarized the therapeutic targets of cerebral ischemia. To explore more effective methods to treat cerebral ischemia, promote the recovery of brain function, and improve the prognosis of patients.

Identification of hub genes and pathways associated with cellular senescence in diabetic foot ulcers via comprehensive transcriptome analysis.

This research aimed to find important genes and pathways related to cellular senescence (CS) in diabetic foot ulcers (DFU) and to estimate the possible pathways through which CS affects diabetic foot healing. The GSE80178 dataset was acquired from the Gene Expression Omnibus (GEO) database, containing six DFU and three diabetic foot skin (DFS) samples. The limma package was used to identify differentially expressed genes (DEGs). At the same time, DEGs associated with CS (CS-DEGs) were found using the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the CS-DEGs. A protein-protein interaction (PPI) network was built using the String database, and the cytoHubba plug-in within Cytoscape helped identify hub genes. Lastly, the miRNA-TF-mRNA regulatory network for these hub genes was established. In total, 66 CS-DEGs were obtained. These genes mainly focus on CS, Kaposi sarcoma-associated herpesvirus infection and Toll-like receptor signalling pathway. Eight hub genes were identified to regulate cell senescence in DFU, including TP53, SRC, SIRT1, CCND1, EZH2, CXCL8, AR and CDK4. According to miRNA-TF-mRNA regulatory network, hsa-mir-132-3p/SIRT1/EZH2 axis is involved in senescence cell accumulation in DFU.

Small RNA Sequencing Analysis of STZ-Injured Pancreas Reveals Novel MicroRNA and Transfer RNA-Derived RNA with Biomarker Potential for Diabetes Mellitus.

MicroRNAs (miRNAs) and transfer RNA-derived small RNAs (tsRNAs) play critical roles in the regulation of different biological processes, but their underlying mechanisms in diabetes mellitus (DM) are still largely unknown. This study aimed to gain a better understanding of the functions of miRNAs and tsRNAs in the pathogenesis of DM. A high-fat diet (HFD) and streptozocin (STZ)-induced DM rat model was established. Pancreatic tissues were obtained for subsequent studies. The miRNA and tsRNA expression profiles in the DM and control groups were obtained by RNA sequencing and validated with quantitative reverse transcription-PCR (qRT-PCR). Subsequently, bioinformatics methods were used to predict target genes and the biological functions of differentially expressed miRNAs and tsRNAs. We identified 17 miRNAs and 28 tsRNAs that were significantly differentiated between the DM and control group. Subsequently, target genes were predicted for these altered miRNAs and tsRNAs, including Nalcn, Lpin2 and E2f3. These target genes were significantly enriched in localization as well as intracellular and protein binding. In addition, the results of KEGG analysis showed that the target genes were significantly enriched in the Wnt signaling pathway, insulin pathway, MAPK signaling pathway and Hippo signaling pathway. This study revealed the expression profiles of miRNAs and tsRNAs in the pancreas of a DM rat model using small RNA-Seq and predicted the target genes and associated pathways using bioinformatics analysis. Our findings provide a novel aspect in understanding the mechanisms of DM and identify potential targets for the diagnosis and treatment of DM.

Identification of potential targets against SARS-CoV-2 of antiviral drugs based on photoaffinity probes.

Facing the sudden outbreak of coronavirus disease 2019 (COVID-19), it is extremely urgent to develop effective antiviral drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Drug repurposing is a promising strategy for the treatment of COVID-19. To identify the precise target protein of marketed medicines, we initiate a chemical biological program to identify precise target of potential antivirus drugs. In this study, two types of recombinant human coronavirus SARS-CoV-2 RdRp protein capturing probes with various photoaffinity labeling units were designed and synthesized based on the structure of FDA-approved drugs stavudine, remdesivir, acyclovir, and aladenosine. Fortunately, it was found that one novel photoaffinity probe, RD-1, could diaplayed good affinity with SARS-CoV-2 RdRp around the residue ARG_553. In addition, RD-1 probe also exhibited potent inhibitory activity against 3CLpro protease. Taken together, our findings will elucidate the structural basis for the efficacy of marketed drugs, and explore a rapid and efficient strategy of drug repurposing based on the identification of new targets. Moreover, these results could also provide a scientific basis for the clinical application of marketed drugs.

The role of autophagy in cardiovascular disease: Cross-interference of signaling pathways and underlying therapeutic targets.

Autophagy is a conserved lysosomal pathway for the degradation of cytoplasmic proteins and organelles, which realizes the metabolic needs of cells and the renewal of organelles. Autophagy-related genes (ATGs) are the main molecular mechanisms controlling autophagy, and their functions can coordinate the whole autophagic process. Autophagy can also play a role in cardiovascular disease through several key signaling pathways, including PI3K/Akt/mTOR, IGF/EGF, AMPK/mTOR, MAPKs, p53, Nrf2/p62, Wnt/ß-catenin and NF-κB pathways. In this paper, we reviewed the signaling pathway of cross-interference between autophagy and cardiovascular diseases, and analyzed the development status of novel cardiovascular disease treatment by targeting the core molecular mechanism of autophagy as well as the critical signaling pathway. Induction or inhibition of autophagy through molecular mechanisms and signaling pathways can provide therapeutic benefits for patients. Meanwhile, we hope to provide a unique insight into cardiovascular treatment strategies by understanding the molecular mechanism and signaling pathway of crosstalk between autophagy and cardiovascular diseases.

Status quo of current clinical drug regimens for small cell lung cancer and new progress in the potential target drug therapeutic regimens / 中国药房

Small cell lung cancer （SCLC） accounts for about 15% in lung cancer and is highly malignant， heterogeneous and invasive. Etoposide combined with platinum-based chemotherapy is the basis of standard first-line treatment for extensive-stage SCLC， but suffers from the problem of susceptibility to drug resistance and relapse. In recent years， the emergence of new immunological drugs and novel cytotoxic drugs has improved the survival of SCLC patients to a certain extent， especially bringing therapeutic hope to patients with relapsed/refractory SCLC. In this paper， we review the current clinical drug regimens and the new progress of potential target drug therapeutic regimens for the treatment of SCLC. At present， the first-， second- and third-line schemes of SCLC include etoposide+carboplatin， atezolizumab+etoposide+platinum， adebrelimab， topotecan， docetaxel， etc.； the current drug targets for the treatment of SCLC mainly focus on topoisomerase Ⅱ/Ⅰ， DNA， the immune checkpoint molecules programmed death-1/programmed death-ligand 1， tubulin， etc. The potential target drug therapeutic options include alisertib+ paclitaxel， rovalpituzumab， APG-1252， etc.， and mainly focus on DNA damage response pathways and immune pathways， which can achieve the prolongation of patient survival by exerting anti-tumor effects through aurora kinase A and other potential targets.

Tertiary lymphoid structures in autoimmune diseases.

Tertiary lymphoid structures (TLSs) are organized lymphoid-like aggregations in non-lymphoid tissues. Tissues with chronic and persistent inflammation infiltration may drive and form ectopic germinal center-like structures, which are very common in autoimmune diseases, chronic infections, and tumor microenvironments. However, the mechanisms governing the formation of TLSs are still being explored. At present, it is not clear whether the formation of TLSs is associated with local uncontrolled immune inflammatory responses. While TLSs suggest a good prognosis in tumors, the opposite is true in autoimmune diseases. This review article will discuss the current views on initiating and maintaining TLSs and the potential therapeutic target in autoimmune diseases.

Comparative Transcriptome Reveals the Potential Modulation Mechanisms of Spdsx Affecting Ovarian Development of Scylla paramamosain.

In previous study, we reported the identification, tissue distribution, and the roles of Spdsx played in the testis, androgenic gland, and ovary in Scylla paramamosain. Here, we primally identify its potential target genes in the ovary with RNAi and RNA-Seq technology. By comparing the transcriptome data of two groups (ovaries that injected with dsRNA for EGFP and Dsx), we found that 6520 Unigenes were differentially expressed, including a plenty of conserved crucial genes involved in ovarian development, such as vitellogenin (vtg), vtg receptor (vtgR), apolipoprotein D, adenylate cyclase 3, adenylate cyclase 5, cyclin A, cyclin B, and cell division cycle 2 (cdc2). In addition, these DEGs were also enriched in pathways related to ovary development, including PI3K-Akt signaling pathway, MAPK signaling pathway, insulin signaling pathway, Wnt signaling pathway, relaxin signaling pathway, estrogen signaling pathway, progesterone-mediated oocyte maturation, ovarian steroidogenesis, and oocyte meiosis. Moreover, several genes were selected for qRT-PCR to validate the accuracy of the bioinformatic result. According to current transcriptome result, we speculate that the Spdsx is a crucial regulator of ovary development in S. paramamosain. To the best of our knowledge, the current study was the first report about dsx function through comparative transcriptome analysis in crustacean species, which not only identified relevant genes and pathways involved in ovarian development of S. paramamosain, but also shed light on the regulatory mechanisms of dsx at the molecular level in crustacean.

Comprehensive analysis of karyopherin alpha family expression in lung adenocarcinoma: Association with prognostic value and immune homeostasis.

Background: Karyopherin alpha (KPNA), a nuclear transporter, has been implicated in the development as well as the progression of many types of malignancies. Immune homeostasis is a multilevel system which regulated by multiple factors. However, the functional significance of the KPNA family in the pathogenesis of lung adenocarcinoma (LUAD) and the impact of immune homeostasis are not well characterized. Methods: In this study, by integrating the TCGA-LUAD database and Masked Somatic Mutation, we first conducted an investigation on the expression levels and mutation status of the KPNA family in patients with LUAD. Then, we constructed a prognostic model based on clinical features and the expression of the KPNA family. We performed functional enrichment analysis and constructed a regulatory network utilizing the differential genes in high-and low-risk groups. Lastly, we performed immune infiltration analysis using CIBERSORT. Results: Analysis of TCGA datasets revealed differential expression of the KPNA family in LUAD. Kaplan-Meier survival analyses indicated that the high expression of KPNA2 and KPNA4 were predictive of inferior overall survival (OS). In addition, we constructed a prognostic model incorporating clinical factors and the expression level of KPNA4 and KPNA5, which accurately predicted 1-year, 3-years, and 5-years survival outcomes. Patients in the high-risk group showed a poor prognosis. Functional enrichment analysis exhibited remarkable enrichment of transcriptional dysregulation in the high-risk group. On the other hand, gene set enrichment analysis (GSEA) displayed enrichment of cell cycle checkpoints as well as cell cycle mitotic in the high-risk group. Finally, analysis of immune infiltration revealed significant differences between the high-and low-risk groups. Further, the high-risk group was more prone to immune evasion while the inflammatory response was strongly associated with the low-risk group. Conclusions: the KPNA family-based prognostic model reflects many biological aspects of LUAD and provides potential targets for precision therapy in LUAD.

Sigma-1 receptor: A potential target for the development of antidepressants.

Though a great many of studies on the development of antidepressants for the therapy of major depression disorder (MDD) and the development of antidepressants have been carried out, there still lacks an efficient approach in clinical practice. The involvement of Sigma-1 receptor in the pathological process of MDD has been verified. In this review, recent research focusing on the role of Sigma-1 receptor in the etiology of MDD were summarized. Preclinical studies and clinical trials have found that stress induce the variation of Sigma-1 receptor in the blood, brain and heart. Dysfunction and absence of Sigma-1 receptor result in depressive-like behaviors in rodent animals. Agonists of Sigma-1 receptor show not only antidepressant-like activities but also therapeutical effects in complications of depression. The mechanisms underlying antidepressant-like effects of Sigma-1 receptor may include suppressing neuroinflammation, regulating neurotransmitters, ameliorating brain-derived neurotrophic factor and N-Methyl-D-Aspartate receptor, and alleviating the endoplasmic reticulum stress and mitochondria damage during stress. Therefore, Sigma-1 receptor represents a potential target for antidepressants development.

Pepper Mild Mottle Virus Coat Protein as a Novel Target to Screen Antiviral Drugs.

Pepper mild mottle virus (PMMoV) has caused serious economic losses to crop production in many countries. The coat protein (CP) of PMMoV is a multifunctional protein proved to be a determining factor in the assignment of virulence type. Therefore, we studied the interaction between drugs and PMMoV CP as a method to screen anti-PMMoV agents. In this study, vanisulfane (6f) exhibited good inactivation activity (68.5%) by biological activity screening. Meanwhile, the green fluorescent protein and PMMoV CP expression changes of vanisulfane against PMMoV were verified by western blot and qRT-PCR experiments. The affinity between vanisulfane and PMMoV CP was predicted to be the best by autodocking and molecular dynamics simulation. PMMoV CP was purified for the first time from the soluble fraction, and the strong affinity between vanisulfane and CP was further verified by interaction experiments. Therefore, this study found that vanisulfane is a potential anti-PMMoV drug targeting PMMoV CP.

Chemical Diversity and Potential Target Network of Woody Peony Flower Essential Oil from Eleven Representative Cultivars (Paeonia × suffruticosa Andr.).

Woody peony (Paeonia × suffruticosa Andr.) has many cultivars with genetic variances. The flower essential oil is valued in cosmetics and fragrances. This study was to investigate the chemical diversity of essential oils of eleven representative cultivars and their potential target network. Hydro-distillation afforded yields of 0.11-0.25%. Essential oils were analyzed by GC-MS and GC-FID which identified 105 compounds. Three clusters emerged from multivariate analysis, representative of phloroglucinol trimethyl ether ('Caihui'), citronellol ('Jingyu', 'Zhaofen' and 'Baiyuan Zhenghui') and mixed (the rest of the cultivars) chemotypes. 'Zhaofen' and 'Jingyu' also exhibited low levels of other rose-related compounds. The main components were subjected to a target network approach. Drug-likeness screening gave 20 compounds with predictive blood-brain barrier permeation. Compound target network identified six key compounds, namely nerol, citronellol, geraniol, geranic acid, cis-3-hexen-1-ol and 1-hexanol. Top enriched terms in GO, KEGG and DisGeNET were mostly related to the central nervous system (CNS). Protein-protein interactions revealed a core network of 14 targets, 11 of which were CNS-related (targets for antidepressants, analgesics, antipsychotics, anti-Alzheimer's and anti-Parkinson's agents). This work provides useful information on the production of woody peony essential oils with specific chemotypes and reveals their potential importance in aromatherapy for alternative treatment of CNS disorders.

Advances in Pathogenesis, Progression, Potential Targets and Targeted Therapeutic Strategies in SARS-CoV-2-Induced COVID-19.

As the new year of 2020 approaches, an acute respiratory disease quietly caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as coronavirus disease 2019 (COVID-19) was reported in Wuhan, China. Subsequently, COVID-19 broke out on a global scale and formed a global public health emergency. To date, the destruction that has lasted for more than two years has not stopped and has caused the virus to continuously evolve new mutant strains. SARS-CoV-2 infection has been shown to cause multiple complications and lead to severe disability and death, which has dealt a heavy blow to global development, not only in the medical field but also in social security, economic development, global cooperation and communication. To date, studies on the epidemiology, pathogenic mechanism and pathological characteristics of SARS-CoV-2-induced COVID-19, as well as target confirmation, drug screening, and clinical intervention have achieved remarkable effects. With the continuous efforts of the WHO, governments of various countries, and scientific research and medical personnel, the public's awareness of COVID-19 is gradually deepening, a variety of prevention methods and detection methods have been implemented, and multiple vaccines and drugs have been developed and urgently marketed. However, these do not appear to have completely stopped the pandemic and ravages of this virus. Meanwhile, research on SARS-CoV-2-induced COVID-19 has also seen some twists and controversies, such as potential drugs and the role of vaccines. In view of the fact that research on SARS-CoV-2 and COVID-19 has been extensive and in depth, this review will systematically update the current understanding of the epidemiology, transmission mechanism, pathological features, potential targets, promising drugs and ongoing clinical trials, which will provide important references and new directions for SARS-CoV-2 and COVID-19 research.

Potential Target Analysis of Triptolide Based on Transcriptome-Wide m6A Methylome in Rheumatoid Arthritis.

Triptolide (TP), a major active component of the herb Tripterygium wilfordii Hook F (TwHF), has been shown to exert therapeutic potential against rheumatoid arthritis (RA). However, its molecular mechanism of action has not been fully elucidated. This study aimed to analyze the potential target of TP based on the discovery of differentially methylated and expressed genes (DMEGs) in RA using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq). Five RA samples and ten control samples were obtained from China-Japan Friendship Hospital. The various levels of m6A methylation and genes expressed in the RA and control groups were compared by MeRIP-seq and RNA-seq. Bioinformatics explorations were also performed to explore the enriched biological roles and paths of the differentially expressed m6A methylation and genes. Molecular networks between TP target proteins and DMEGs were performed using Ingenuity Pathway Analysis (IPA) software. Potential target of TP was determined with Gene Expression Omnibus (GEO) database mining, molecular docking, and in vitro experiment validation. In total, 583 dysregulated m6A peaks, of which 295 were greatly upregulated and 288 were greatly downregulated, were identified. Similarly, 1,570 differentially expressed genes were identified by RNA-seq, including 539 upregulated and 1,031 downregulated genes. According to the deeper joint exploration, the m6A methylation and mRNA expression degrees of 35 genes varied greatly. Molecular networks between TP target proteins and DMEGs were constructed, and the results revealed that tubulin beta-2A chain (TUBB2A), insulin-like growth factor 2 mRNA-binding protein 3 (IGF2BP3), cytoplasmic dynein 1 intermediate chain 1 (DYNC1I1), and FOS-like 1 (FOSL1) were the most relevant genes that correlated with the target proteins of TP. The results of the GEO database showed that the gene expression of IGF2BP3 was increased in RA synovial tissue and consistent with the trend of our sequencing results of RA PBMCs. Molecular docking and in vitro experiment suggested that TP and IGF2BP3 had a high binding affinity and TP could decrease the mRNA expression of IGF2BP3 in PBMCs and MH7A.This research established a transcriptional map of m6A in RA PBMCs and displayed the hidden association between RNA methylation alterations and associated genes in RA. IGF2BP3 might be a potential therapeutic target of TP during RA treatment.

PIWI­interacting RNA in cancer: Molecular mechanisms and possible clinical implications (Review).

PIWI­interacting RNA is a class of non­coding small RNA that is ~30 nt long and is primarily found in mammalian germ cells from mice and humans. In cooperation with the members of PIWI protein family, this macromolecule participates in germ cell development, inhibits DNA self­-replication and maintains genomic stability. Increasing evidence has demonstrated that PIWI­interacting RNA (piRNAs) are abnormally expressed in various human cancers, such as liver cancer, stomach cancer, colorectal cancer, osteosarcoma, breast cancer, lung cancer, prostate cancer, etc. piRNAs abnormal expression is also associated with the occurrence and development of human cancers, such as liver cancer, stomach cancer, colorectal cancer, etc. Despite their unclear molecular mechanisms, piRNAs may act as oncogenes or tumor suppressors by interacting with multiple cancer­related signal pathways including STAT3/Bcl­xl or coding genes, such as heat shock transcription factor­1. Hence, piRNAs may be potential markers and targets and provide new opportunities for cancer diagnosis, treatment or prognosis monitoring. The current review mainly aims to highlight the latest research progress made in the biological functions and regulation of piRNAs in mammals, their involvement in various cancer forms and their potential clinical applications.

Glioma glycolipid metabolism: MSI2-SNORD12B-FIP1L1-ZBTB4 feedback loop as a potential treatment target.

Abnormal energy metabolism, including enhanced aerobic glycolysis and lipid synthesis, is a well-established feature of glioblastoma (GBM) cells. Thus, targeting the cellular glycolipid metabolism can be a feasible therapeutic strategy for GBM. This study aimed to evaluate the roles of MSI2, SNORD12B, and ZBTB4 in regulating the glycolipid metabolism and proliferation of GBM cells. MSI2 and SNORD12B expression was significantly upregulated and ZBTB4 expression was significantly low in GBM tissues and cells. Knockdown of MSI2 or SNORD12B or overexpression of ZBTB4 inhibited GBM cell glycolipid metabolism and proliferation. MSI2 may improve SNORD12B expression by increasing its stability. Importantly, SNORD12B increased utilization of the ZBTB4 mRNA transcript distal polyadenylation signal in alternative polyadenylation processing by competitively combining with FIP1L1, which decreased ZBTB4 expression because of the increased proportion of the 3' untranslated region long transcript. ZBTB4 transcriptionally suppressed the expression of HK2 and ACLY by binding directly to the promoter regions. Additionally, ZBTB4 bound the MSI promoter region to transcriptionally suppress MSI2 expression, thereby forming an MSI2/SNORD12B/FIP1L1/ZBTB4 feedback loop to regulate the glycolipid metabolism and proliferation of GBM cells. In conclusion, MSI2 increased the stability of SNORD12B, which regulated ZBTB4 alternative polyadenylation processing by competitively binding to FIP1L1. Thus, the MSI2/SNORD12B/FIP1L1/ZBTB4 positive feedback loop plays a crucial role in regulating the glycolipid metabolism of GBM cells and provides a potential drug target for glioma treatment.

Identification of potential therapeutic target of naringenin in breast cancer stem cells inhibition by bioinformatics and in vitro studies.

Cancer therapy is a strategic measure in inhibiting breast cancer stem cell (BCSC) pathways. Naringenin, a citrus flavonoid, was found to increase breast cancer cells' sensitivity to chemotherapeutic agents. Bioinformatics study and 3D tumorsphere in vitro modeling in breast cancer (mammosphere) were used in this study, which aims to explore the potential therapeutic targets of naringenin (PTTNs) in inhibiting BCSCs. Bioinformatic analyses identified direct target proteins (DTPs), indirect target proteins (ITPs), naringenin-mediated proteins (NMPs), BCSC regulatory genes, and PTTNs. The PTTNs were further analyzed for gene ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, protein-protein interaction (PPI) networks, and hub protein selection. Mammospheres were cultured in serum-free media. The effects of naringenin were measured by MTT-based cytotoxicity, mammosphere forming potential (MFP), colony formation, scratch wound-healing assay, and flow cytometry-based cell cycle analyses and apoptosis assays. Gene expression analysis was performed using real-time quantitative polymerase chain reaction (q-RT PCR). Bioinformatics analysis revealed p53 and estrogen receptor alpha (ERα) as PTTNs, and KEGG pathway enrichment analysis revealed that TGF-ß and Wnt/ß-catenin pathways are regulated by PTTNs. Naringenin demonstrated cytotoxicity and inhibited mammosphere and colony formation, migration, and epithelial to mesenchymal transition in the mammosphere. The mRNA of tumor suppressors P53 and ERα were downregulated in the mammosphere, but were significantly upregulated upon naringenin treatment. By modulating the P53 and ERα mRNA, naringenin has the potential of inhibiting BCSCs. Further studies on the molecular mechanism and formulation of naringenin in BCSCs would be beneficial for its development as a BCSC-targeting drug.

Overexpression of Ubiquitin-Specific Protease15 (USP15) Promotes Tumor Growth and Inhibits Apoptosis and Correlated With Poor Disease-Free Survival in Hepatocellular Carcinoma.

USP15 is a member of ubiquitin-specific proteases (USPs, the largest subfamily of deubiquitinases) and functions as a stabilize factor of target proteins in reversible ubiquitiantion progression. Dysregulated expression of USP15 has been observed in various cancers. However the expression profile and regulatory mechanism of USP15 in hepatocellular carcinoma (HCC) remains largely elusive. To exam the USP15 expression changes in the progression of HCC, we performed IHC analysis to test USP15 expression in a series of cancer-prone diseases including 2 normal liver tissues, 6 liver cirrhosis, 16 primary liver lesions and 15 metastases of hepatocellular carcinoma. The expression of USP15 was upregulated in various liver diseases in compared with normal tissue significantly (p < 0.05). Although no significant different of USP15 expression were discovered between cirrhotic tissue and primary tissue, its expression in HCC metastatic tissue was upregulated. Subsequently, we test the USP15 expression profile in a cohort of 66 HCC patients. USP15 expression was positively correlated with the recurrence of HCC significantly (p = 0.004). HCC patients with high USP15 expression had shorter disease free survival time in compare with those with low USP15 expression (56.9% VS 26.7%, P = 0.012). Subsequently, Cox multivariate analyses of clinical factors associated with disease free survival were performed and USP15 expression (p = 0.008) together with tumor size (p = 0.034) were proved to be independent predict factors in HCC. Then, we silenced USP15 expression in HCC cells and the results showed that downregulated USP15 expression resulting proliferation inhibition and apoptosis induction. In conclusion, our results suppose USP15 to be a potential target in HCC.