Structural analysis of PTPN21 reveals a dominant-negative effect of the FERM domain on its phosphatase activity.

PTPN21 belongs to the four-point-one, ezrin, radixin, moesin (FERM) domain-containing protein tyrosine phosphatases (PTP) and plays important roles in cytoskeleton-associated cellular processes like cell adhesion, motility, and cargo transport. Because of the presence of a WPE loop instead of a WPD loop in the phosphatase domain, it is often considered to lack phosphatase activity. However, many of PTPN21's biological functions require its catalytic activity. To reconcile these findings, we have determined the structures of individual PTPN21 FERM, PTP domains, and a complex between FERM-PTP. Combined with biochemical analysis, we have found that PTPN21 PTP is weakly active and is autoinhibited by association with its FERM domain. Disruption of FERM-PTP interaction results in enhanced ERK activation. The oncogenic HPV18 E7 protein binds to PTP at the same location as PTPN21 FERM, indicating that it may act by displacing the FERM domain from PTP. Our results provide mechanistic insight into PTPN21 and benefit functional studies of PTPN21-mediated processes.

Bufalin inhibits the proliferation of lung cancer cells by suppressing Hippo-YAP pathway.

Lung cancer has high morbidity and mortality. This study demonstrated that Bufalin inhibits the proliferation of lung cancer cells in vivo / in vitro by suppressing Hippo-YAP pathway. Here, we found that Bufalin promoted the binding of LATS and YAP to elevate the level of YAP phosphorylation. Phosphorylated YAP could not successfully enter the nucleus to activate the expression of downstream proliferation-related target genes Cyr61 and CTGF, whereas the YAP retained in the cytoplasm further bound to ß-TrCP and underwent ubiquitination and degradation. This study verified the key role of YAP in stimulating the proliferation of lung cancer and revealed the anticancer target of Bufalin. Therefore, this study provides a theoretical basis for the anticancer effect of Bufalin, and suggests that Bufalin can be a potential anticancer drug.

The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC.

Chemotherapy for advanced non-small-cell lung cancer (NSCLC) remains the first treatment choice. Angiogenesis inhibitors are effective for lung cancer treatment. This study explored whether chemotherapy combined with angiogenesis inhibitors could achieve better efficacy in NSCLC. The zebrafish A549 xenograft model was used to investigate the combined effect of apatinib and chemotherapeutic agents in NSCLC. Apatinib combined with pemetrexed demonstrated the highest antitumor effect compared with apatinib combined with gemcitabine or paclitaxel in vitro. In the zebrafish A549 xenograft model, apatinib and pemetrexed, alone or in combination, showed significant inhibition of tumor growth. Co-treatment with apatinib and pemetrexed demonstrated the best antitumor effects, suggesting that the combination of apatinib and pemetrexed might be a promising alternative therapy for patients with lung cancer. Apatinib combined with pemetrexed had enhanced antitumor effects compared with either one alone in the zebrafish model of NSCLC.

Autophagy Balances Neuroinflammation in Alzheimer's Disease.

Autophagy is a highly evolutionary conserved process that degrades cytosolic macromolecules or damaged organelles (e.g., mitochondria), as well as intracellular pathogens for energy and survival. Dysfunction of autophagy has been associated with the pathologies of Alzheimer's disease (AD), including Aß plaques and neurofibrillary tangles. Recently, the presence of sustained immune response in the brain has been considered a new core pathology in AD. Accumulating evidence suggests that autophagy activation may suppress inflammation response through degrading inflammasomes or pro-inflammatory cytokines and improving immune system function in both clinical trials and preclinical studies. This review provides an overview of updated information on autophagy and inflammation and their potential mediators in AD. In summary, we believe that understanding the relationship between autophagy and inflammation will provide insightful knowledge for future therapeutic implications in AD.

CEBPA mutants down-regulate AML cell susceptibility to NK-mediated lysis by disruption of the expression of NKG2D ligands, which can be restored by LSD1 inhibition.

NK group 2, member D (NKG2D) is one of the most critical activating receptors expressed by natural killer (NK) cells. There is growing evidence that acute myeloid leukemia (AML) cells may evade NK cell-mediated cell lysis by expressing low or no ligands for NKG2D (NKG2D-Ls). We hypothesized that CCAAT/enhancer-binding protein α (C/EBPα), one of the most studied lineage-specific transcription factors in hematopoiesis, might influence the expression of NKG2D-Ls. To test this hypothesis, we first examined the endogenous expression of wild-type C/EBPα (C/EBPα-p42) in human AML cell lines and demonstrated that its expression level was highly relevant to the sensitivity of AML cells to NK cell cytotoxicity. Induction of C/EBPα-p42 in the low endogenous CEBPA-expressing AML cell line increased the sensitivity to NK-induced lysis. Moreover, decreased expression of C/EBPα-p42 by RNA interference in AML cells abrogated NK-mediated cytotoxicity. We further showed that the increase in NK susceptibility caused by C/EBPα-p42 occurred through up-regulation of the NKG2D-Ls ULBP2/5/6 in AML cells. More importantly, chromatin immunoprecipitation (ChIP) coupled with high-throughput sequencing captured C/EBPα motif signatures at the enhancer regions of the ULBP 2/5/6 genes. Whilst, the AML-associated C/EBPα C-terminal mutant and N-terminal truncated mutant (C/EBPα-p30) diminished ULBP2/5/6 transcription. Finally, we identified that histone demethylase lysine-specific demethylase 1 (LSD1) inhibition can restore the expression of ULBPs via induction of CEBPA expression in AML cells, which may represent a novel therapeutic strategy for CEBPA-mutated AML. Abbreviations: C/EBPα: CCAAT/enhancer-binding protein α; TF: Transcription factor; AML: Acute myeloid leukemia; TAD: Transactivation domain; FS: Frameshift; NK: Natural killer; NKG2D: NK group 2, member D; NKG2D-Ls: Ligands for NKG2D; MHC: Major histocompatibility complex; MICA: MHC class I-related chain A; ULBP: UL16-binding protein; STAT3: Signal transducer and activator of transcription 3; LSD1: Lysine-specific demethylase 1; Ab: Antibody; PBMC: Peripheral blood mononuclear cell; PBS: Phosphate-buffered saline; CFSE: Carboxyfluorescein diacetate succinimidyl ester; PI: Propidium iodide; shRNA: Short hairpin RNA; ChIP: Chromatin immunoprecipitation; BM: Binding motif; HCNE: Highly conserved noncoding element; TSS: Transcription start site; HMA: Hypomethylating agent; AZA: Azacitidine/5-azacytidine; DAC: Decitabine/5-aza-29-deoxycytidine; 2-PCPA: Tranylcypromine; RBP: RNA-binding protein; MSI2: MUSASHI-2; HDACi: Inhibitor of histone deacetylases; VPA: Valproate; DNMTi: DNA methyl transferase inhibitor; SCLC: Small cell lung cancer.

Successful Treatment of Relapsed/Refractory Extramedullary Multiple Myeloma With Anti-BCMA CAR-T Cell Therapy Followed by Haploidentical Hematopoietic Stem Cell Transplantation: A Case Report and a Review of the Contemporary Literature.

Extramedullary multiple myeloma (EMM) is an aggressive sub-entity of multiple myeloma (MM). Despite an excellent improvement in survival for most patients with MM over recent decades, the overall survival (OS) of patients with EMM was usually not longer than 3 years. Standard treatment for patients with EMM has not been established, and their management is particularly challenging. We presented a heavily pretreated young patient with relapsed EMM and refractoriness to a proteasome inhibitor (PI; bortezomib), a next-generation PI (ixazomib), immunomodulatory drugs (IMiDs; lenalidomide), autologous hematopoietic stem cell transplantation (ASCT), and monoclonal antibody (directed against CD38: daratumumab) and indicated that myeloablative haploidentical hematopoietic stem cell transplantation (haploidentical-HSCT) as a salvage treatment of relapse after a chimeric antigen receptor (CAR)-T cell therapy that targeted B-cell maturation antigen (BCMA) (NCT04650724) is feasible. Taken together of the contemporary literature, the promising results on the effect of anti-BCMA CAR-T cell therapy and allogeneic HSCT might present a proof-of-principle for patients with EMM, and therefore, patients with the disease need to be included in future studies.

Endogenous glutamate determines ferroptosis sensitivity via ADCY10-dependent YAP suppression in lung adenocarcinoma.

Rationale: Ferroptosis, a newly identified form of regulated cell death, can be induced following the inhibition of cystine-glutamate antiporter system XC- because of the impaired uptake of cystine. However, the outcome following the accumulation of endogenous glutamate in lung adenocarcinoma (LUAD) has not yet been determined. Yes-associated protein (YAP) is sustained by the hexosamine biosynthesis pathway (HBP)-dependent O-linked beta-N-acetylglucosaminylation (O-GlcNAcylation), and glutamine-fructose-6-phosphate transaminase (GFPT1), the rate-limiting enzyme of the HBP, can be phosphorylated and inhibited by adenylyl cyclase (ADCY)-mediated activation of protein kinase A (PKA). However, whether accumulated endogenous glutamate determines ferroptosis sensitivity by influencing the ADCY/PKA/HBP/YAP axis in LUAD cells is not understood. Methods: Cell viability, cell death and the generation of lipid reactive oxygen species (ROS) and malondialdehyde (MDA) were measured to evaluate the responses to the induction of ferroptosis following the inhibition of system XC-. Tandem mass tags (TMTs) were employed to explore potential factors critical for the ferroptosis sensitivity of LUAD cells. Immunoblotting (IB) and quantitative RT-PCR (qPCR) were used to analyze protein and mRNA expression. Co-immunoprecipitation (co-IP) assays were performed to identify protein-protein interactions and posttranslational modifications. Metabolite levels were measured using the appropriate kits. Transcriptional regulation was evaluated using a luciferase reporter assay, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA). Drug administration and limiting dilution cell transplantation were performed with cell-derived xenograft (CDX) and patient-derived xenograft (PDX) mouse models. The associations among clinical outcome, drug efficacy and ADCY10 expression were determined based on data from patients who underwent curative surgery and evaluated with patient-derived primary LUAD cells and tissues. Results: The accumulation of endogenous glutamate following system XC- inhibition has been shown to determine ferroptosis sensitivity by suppressing YAP in LUAD cells. YAP O-GlcNAcylation and expression cannot be sustained in LUAD cells upon impairment of GFPT1. Thus, Hippo pathway-like phosphorylation and ubiquitination of YAP are enhanced. ADCY10 acts as a key downstream target and diversifies the effects of glutamate on the PKA-dependent suppression of GFPT1. We also discovered that the protumorigenic and proferroptotic effects of ADCY10 are mediated separately. Advanced-stage LUADs with high ADCY10 expression are sensitive to ferroptosis. Moreover, LUAD cells with acquired therapy resistance are also prone to higher ADCY10 expression and are more likely to respond to ferroptosis. Finally, a varying degree of secondary labile iron increase is caused by the failure to sustain YAP-stimulated transcriptional compensation for ferritin at later stages further explains why ferroptosis sensitivity varies among LUAD cells. Conclusions: Endogenous glutamate is critical for ferroptosis sensitivity following the inhibition of system XC- in LUAD cells, and ferroptosis-based treatment is a good choice for LUAD patients with later-stage and/or therapy-resistant tumors.

Exosomes-transmitted miR-7 reverses gefitinib resistance by targeting YAP in non-small-cell lung cancer.

Epidermal growth factor receptor (EGFR) T790M mutation act as the dominant resistance mechanism to first and second generations tyrosine kinase inhibitors (TKIs), the roles of miR-7 in the development of T790M mutation are largely unknown. Here, we confirmed that the level of miR-7 was significantly higher in the gefitinib sensitivity PC9 cells compared to gefitinib resistance H1975 cells, and miR-7 overexpression promoted the apoptosis of H1975 cells by gefitinib treatment. Furthermore, we found that exosomes could transfer miR-7 mimics from PC9 cells to H1975 cells, which reversed gefitinib resistance through binding to YAP, and altered H1975 cells resistance phenotype in vitro. In addition, we suppressed exosomal miR-7 by GW4869, increasing PC9 cells chemoresistance to gefitinib treatment in vivo. Of note, we detected that miR-7 was significantly higher in serum exosomes from healthy controls than from patients with lung carcinoma, and high miR-7 expression was associated with strong response to lung carcinoma patients receiving gefitinib treatment, as well as a longer survival. Therefore, exosomal miR-7 can act as a potential biomarker and therapeutic target for EGFR T79M resistance mutations.

Huaier Suppresses the Hepatocellular Carcinoma Cell Cycle by Regulating Minichromosome Maintenance Proteins.

PURPOSE: Hepatocellular carcinoma (HCC) is a common malignant tumor with limited treatment. Our previous studies demonstrated that Huaier enhanced chemotherapy sensitivity and restrained HCC proliferation. This study aimed to identify differentially expressed proteins with Huaier treatment in HCC cells, providing molecular targets for future targeted therapy of HCC. MATERIALS AND METHODS: The effects of Huaier on the cell cycle were determined by flow cytometry and Western blot (WB). Xenograft models were used to verify the effects of Huaier on tumor growth. Then, proteomics was performed to identify the potential proteins regulated by Huaier. The enrichment analysis of GO and KEGG was performed for the differentially expressed proteins. Western blot (WB) and immunohistochemistry (IHC) were used to detect the levels of proteins after Huaier treatment. After that the correlation of differentially expressed proteins with pathological stages was analyzed via the GEPIA database. We also analyzed candidate expression after Huaier treatment in HCC cells by WB and qRT-PCR. Furthermore, siRNA was performed to verify the targeted regulation of Huaier on candidate proteins. RESULTS: First, the proteomics data showed that a total of 160 proteins were identified as differentially expressed proteins, among which six minichromosome maintenance (MCM) family members were enriched in the tumor-associated pathways after Huaier treatment. Moreover, MCM proteins were highly expressed in HCC and closely correlated with the survival of HCC patients. Finally, we confirmed that MCM proteins were targets of Huaier treatment in HCC cells. CONCLUSION: Huaier treatment was closely associated with the activation and inhibition of cancer-related pathways, and the MCM family was identified as a potential target in the antitumor process of Huaier. This study is helpful in understanding the molecular alterations and clinical relevance of HCC after Huaier treatment, which is beneficial for finding new targets and designing effective chemotherapy regimens for the future treatment of HCC.

The biological functions and clinical applications of exosomes in lung cancer.

Lung cancer remains the leading cause of cancer-related death worldwide, and the high incidence rates are worrisome. Exosomes are a class of extracellular vesicles secreted by most cells, including RNAs, proteins and lipids. Exosomes can mediate cell-to-cell communication in both physiologic and pathologic processes. Accumulated evidences show that cancer-derived exosomes aid in the recruitment and reprogramming of constituents correlated with tumor microenvironment. Furthermore, exosome-based clinical trials have been completed in advanced lung cancer patients. In this review, we discuss the roles of exosomes in a lung cancer microenvironment, such as its participation in lung cancer initiation, progression and metastasis as well as being involved in angiogenesis, epithelial-mesenchymal transition (EMT), immune escape, and drug resistance. In addition, we focus on the potential of exosomes as diagnostic and prognostic biomarkers in lung cancer, as well as the challenges faced by and advantages of exosomes as drug delivery vehicles and in exosome-based immunotherapy.

Exosomes in hepatocellular carcinoma: a new horizon.

Exosomes are a class of extracellular vesicles released by multiple cells types including tumor cells, with a size range of 30-100 nm and a lipid bilayer membrane. Recently, the role of exosomes in cell-to-cell communication has been extensively studied, showed that exosomes can deliver their functional RNAs and proteins to recipient cells, impacting transcription and translation of recipient cells. Emerging evidence suggests that hepatocellular carcinoma (HCC) cell-derived exosomes can construct a fertile environment to support HCC cells proliferation, grow, invasion and metastasis, development of drug resistance. Circulating exosomes can be used as noninvasive biomarkers for early diagnosis, moreover as drug delivery vehicles, provide new insights into the treatment of HCC.

Huaier Augmented the Chemotherapeutic Sensitivity of Oxaliplatin via Downregulation of YAP in Hepatocellular Carcinoma.

For unresectable Hepatocellular carcinoma (HCC), chemotherapy is still an important treatment strategy. Oxaliplatin (Oxa) is an effective treatment of HCC after sorafenib treatment failure. However, the intrinsic or acquired resistance of Oxa affected the chemotherapeutic sensitivity. By analyzing the data of GEO Database, we found that Oxa aberrantly increased the expression of Cysteine-rich61 (Cyr61) in HCC cell lines. Subsequently, in Bel-7404 and SMMC-7721 cells after treated with Oxa, it was verified that the expression of Cyr61 and Yes-associated protein (YAP) was increased. Moreover, we found that blockade of YAP promoted Oxa-induced cell apoptosis for the first time. Meanwhile, our previous study demonstrated that Huaier (HE) inhibited the expression of YAP. Further study found that combination treatment of Oxa and HE had a significantly synergistic anti-cancer effect and significantly inhibited the expression of YAP and apoptosis related proteins. Taken together, we have observed that overexpression of YAP significantly reduced the chemotherapeutic sensitivity of Oxa in HCC for the first time. Combination treatment of Oxa and HE solved this problem.

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.

circRNA_104075 stimulates YAP-dependent tumorigenesis through the regulation of HNF4a and may serve as a diagnostic marker in hepatocellular carcinoma.

Some types of circular RNA (circRNA) are aberrantly expressed in human diseases including hepatocellular carcinoma (HCC). However, its regulation mechanism and diagnostic roles are largely unknown. Here, we identified that circRNA_104075 (circ_104075) was highly expressed in HCC tissues, cell lines and serum. Mechanistically, HNF4a bound to the -1409 to -1401 region of the circ_104075 promoter to stimulate the expression of circ_104075. Moreover, circ_104075 acted as a ceRNA to upregulate YAP expression by absorbing miR-582-3p. Interestingly, an N6-methyladenosine (m6A) motif was identified in the 353-357 region of YAP 3'UTR, and this m6A modification was essential for the interaction between miR-582-3p and YAP 3'UTR. Further, the diagnostic performance of circ_104075 was evaluated. The area under the receiver operating characteristic (AUC-ROC) for circ_104075 was 0.973 with a sensitivity of 96.0% and a specificity of 98.3%. Collectively, we determined that circ_104075 was highly expressed in HCC and elucidated its upstream and downstream regulatory mechanisms. circ_104075 additionally has the potential to serve as a new diagnostic biomarker in HCC. Targeting circ_104075 may provide new strategies in HCC diagnosis and therapy.

Monitoring antiangiogenesis of bevacizumab in zebrafish.

Bevacizumab, which is a humanized anti-VEGF antibody, has been successfully applied in clinics since 2004. Bevacizumab in combination with chemotherapy showed high safety and has been applied to solid tumors. However, studies on the insight into the mechanism about the antiangiogenesis activity of bevacizumab were mostly done on mice models, and so there are no visual and intuitive models to observe the process of antiangiogenesis. Here, we first used a zebrafish model to investigate the angiogenesis suppressing behavior of bevacizumab. Our results showed that bevacizumab inhibited formation of zebrafish subintestinal veins, which mimics the process of tumor angiogenesis in vivo. Meanwhile, bevacizumab caused specific vasculature formation defects in subintestinal veins but not in the trunk. Our study also indicated that bevacizumab could inhibit zebrafish retinal angiogenesis with therapeutic potential.

Efficient in situ separation and production of L-lactic acid by Bacillus coagulans using weak basic anion-exchange resin.

To get rid of the dependence on lactic acid neutralizer, a simple and economical approach for efficient in situ separation and production of L-lactic acid was established by Bacillus coagulans using weak basic anion-exchange resin. During ten tested resins, the 335 weak basic anion-exchange resins demonstrated the highest adsorption capacity and selectivity for lactic acid recovery. The adsorption study of the 335 resins for lactic acid confirmed that it is an efficient adsorbent under fermentation condition. Langmuir models gave a good fit to the equilibrium data at 50 °C and the maximum adsorption capacity for lactic acid by 335 resins was about 402 mg/g. Adsorption kinetic experiments showed that pseudo-second-order kinetics model gave a good fit to the adsorption rate. When it was used for in situ fermentation, the yield of L-lactic acid by B. coagulans CC17 was close to traditional fermentation and still maintained at about 82% even after reuse by ten times. These results indicated that in situ separation and production of L-lactic acid using the 335 resins were efficient and feasible. This process could greatly reduce the dosage of neutralizing agent and potentially be used in industry.

Huaier Restrains Proliferative and Migratory Potential of Hepatocellular Carcinoma Cells Partially Through Decreased Yes-Associated Protein 1.

In China, Trametes robiniophila Murr (Huaier), a traditional Chinese herbal medicine, has been widely used in adjuvant therapies of hepatocellular carcinoma (HCC). However, the molecular mechanisms have not been fully understood. The aims of this study are to investigate the functions and mechanisms of Huaier on inhibiting proliferation and migration of HCC cells. Firstly, cell counting kit-8 (CCK-8) and colony formation shown Huaier inhibited proliferation of HCC Bel-7404, Bel-7402 and SMMC-7721 cells in a dose-dependent manner, and this inhibition might be due to Huaier decreased the expressions of the proliferating cell nuclear antigen (PCNA), the nuclear proliferation related antigen (Ki-67) and CyclinD1 detected by western blotting analysis. Notably, we also found Huaier treatment did not cause any cytotoxicity to normal human hepatocyte L-02 cells. Next, we found Huaier dose-dependently decreased Bcl-2 expression and increased Bax expression in Bel-7404 cells. The activities of cleaved caspase substrates had also been enhanced after Huaier treatment, suggesting Huaier treatment could induce HCC cell apoptosis. Then, the inhibitory effects of Huaier on migration of Bel-7404, Bel-7402 and SMMC-7721 cells via inhibiting Epithelial mesenchymal transition (EMT) had also been proved. Moreover, we confirmed yes-associated protein 1 (YAP1) was up-regulated in HCC cells and tissues, and overexpression of YAP1 promoted HCC cell proliferation and migration. Then, western blot and immunefluorescence shown Huaier had the inhibitory effects on YAP1 in HCC cells. On the other hand, human liver cancer tissue microarray (TMA) shown YAP1 expression was closely to clinic. Our study also confirmed Huaier had the inhibitory effects on YAP1 in xenograft mice models, it could be because Huaier treatment translocated YAP1 from nucleus to cytoplasm, and further promoted phosphorylation of YAP1 to be degraded by ubiquitination. Hence, we conclude that Huaier may restrain the proliferation and migration of HCC cells via down-regulation of YAP1. In summary, our study reveals the potential mechanisms of Huaier on inhibiting proliferation and migration of HCC cells. Importantly, for the first time, we found that Huaier can inhibit YAP1 expression in this anti-tumor process. We believe this finding is beneficial for the clinical applications of Huaier and the targeted therapies for HCC.

Increased histone deacetylase 6 expression serves as a favorable prognostic factor for diffuse large B-cell lymphoma.

OBJECTIVE: This study aims to investigate ectopic expression of histone deacetylase 6 (HDAC6) in diffuse large B-cell lymphoma (DLBCL). METHODS: This study analyzed patients with DLBCL (n=132) and reactive lymph node hyperplasia (n=32) diagnosed in our hospital from December 2007 to May 2016. Correlation between HDAC6 expression and clinical pathologic features was analyzed by χ2 test. The significant differences between the 5-year overall survival (OS) or progression-free survival (PFS) and high HDAC6 expression as well as DLBCL clinic-pathological features including age, International Prognostic Index (IPI) score, Eastern Cooperative Oncology Group score, lactate dehydrogenase (LDH), and germinal center B-cell-like were assessed by univariate and multivariate analyses. RESULTS: HDAC6 high-expression percentage in DLBCL was significantly higher than that in the control group. The proportion of IPI score of 0-2, 5-year OS, and PFS in the high-expression group, which had lower percentage of patients with increased LDH and ß2-microglobulin, were significantly higher than those in the low-expression group. Moreover, HDAC6 mRNA expression in HDAC6 protein low expression was markedly lower than that in protein high expression. The multivariate analysis demonstrated that HDAC6 high expression was an independent prognostic factor for patients with DLBCL. CONCLUSION: HDAC6 high expression might be a prognostic factor for DLBCL.