Objective Several epidemiological observational studies have related particulate matter(PM)exposure to Inflammatory bowel disease(IBD),but many confounding factors make it difficult to draw causal links from observational studies.The objective of this study was to explore the causal association between PM2.5 exposure,its absorbance,and IBD. Methods We assessed the association of PM2.5 and PM2.5 absorbance with the two primary forms of IBD(Crohn's disease[CD]and ulcerative colitis[UC])using Mendelian randomization(MR)to explore the causal relationship.We conducted two-sample MR analyses with aggregated data from the UK Biobank genome-wide association study.Single-nucleotide polymorphisms linked with PM2.5 concentrations or their absorbance were used as instrumental variables(IVs).We used inverse variance weighting(IVW)as the primary analytical approach and four other standard methods as supplementary analyses for quality control. Results The results of MR demonstrated that PM2.5 had an adverse influence on UC risk(odds ratio[OR]=1.010;95％confidence interval[CI]=1.001-1.019,P=0.020).Meanwhile,the results of IVW showed that PM2.5 absorbance was also causally associated with UC(OR=1.012;95％CI=1.004-1.019,P=0.002).We observed no causal relationship between PM2.5,PM2.5 absorbance,and CD.The results of sensitivity analysis indicated the absence of heterogeneity or pleiotropy,ensuring the reliability of MR results. Conclusion Based on two-sample MR analyses,there are potential positive causal relationships between PM2.5,PM2.5 absorbance,and UC.

BackgroundHepatocellular carcinoma (HCC) is a major global health challenge with high aggressiveness and recurrence rates. Metabolic reprogramming is a cancer hallmark, enabling tumor cells to sustain rapid growth and evade immune surveillance. Several amino acids have been found to undergo metabolic reprogramming in tumors, and thus are potential anti-tumor targets. However, the characterization and implication of lysine metabolic reprogramming in HCC remain largely unexplored.MethodsWe performed multi-omics profiling, including transcriptomics, proteomics, single-cell omics, immunohistochemistry, and multiplex immunofluorescence on tumor and adjacent normal tissues obtained from 30 HCC patients. Integrative analyses and quantitative evaluations were carried out to characterize the lysine metabolism and investigate its implications for tumor progression, immune microenvironment, and immunotherapy responses.ResultsOur analysis observed a significant downregulation of lysine metabolism in HCC, with inter-patient heterogeneity. Patients with low lysine metabolism in tumors exhibited worse prognoses and a predominance of immunosuppressive tumor immune microenvironment (TIME), characterized by increased infiltration of myeloid-derived suppressor cells (MDSCs), regulatory T cells (Tregs), and exhausted CD8+ T cells (TIM3+CD8+ and LAG3+CD8+). These immunosuppressive cells contribute to immunotherapeutic resistance and promote tumor progression. Notably, our conclusions were consistently supported by observations at both the bulk and single-cell resolutions, as well as T cell receptor (TCR) immune repertoire profiling, reinforcing the robustness of our findings.ConclusionsThis study provides comprehensive evidence that lysine metabolism plays a critical role in shaping the immunosuppressive TIME in HCC and is associated with clinical outcomes and resistance to immunotherapy, offering new insights into clinical molecular subtyping and potential therapeutic strategies.

Magnetic controlled capsule endoscopy (MCE) overcomes limitations of capsule endoscopy and achieves one-time gastro-small intestinal joint examination. However, few studies have reported diagnostic value of MCE of gastrointestinal lesions in patients with abdominal pain. This study aims to investigate clinical applications of MCE in patients with abdominal pain. 465 patients suffered chronic abdominal pain and 366 asymptomatic subjects from two hospitals were included. Patient characteristics, MCE findings, incomplete examinations, examination time and adverse events were evaluated. In the abdominal pain group, disease spectrum was more diverse covering 45 types gastrointestinal lesions. Gastric lesions including atrophic gastritis, erosion, ulcer, carditis, polyp and submucosal tumor, and small intestinal lesions including lymphangiectasia, erosion, ulcer, angiotelectasis, bleeding and Crohn’s disease, had the higher detection rates (all P < 0.05). Some patients detected small intestinal lesions accompanied by diarrhea, weight loss and hematochezia. The abdominal pain group had the lower completion rate and longer transit time (all P < 0.05). In conclusion, MCE is beneficial to detect diverse disease spectrum and atrophic gastritis, ulcer, erosion, Crohn’s disease and small intestinal bleeding in patients with abdominal pain, and to find more lesions as one-time gastro-small intestine joint examination, with efficiency, safety, noninvasiveness and high completion rate.

Gastric cancer is one of the leading causes of cancer mortality worldwide, but the underlying molecular mechanisms by which gastric cancer progresses are not fully understood. While deubiquitinases have emerged as promising therapeutic targets in various cancers, a suitable target deubiquitinase for the treatment of gastric cancer has not yet been identified. Using bioinformatics analyses, we identified that upregulation of ubiquitin-specific peptidase 26 (USP26) was associated with poor patient survival in patients with gastric cancer; moreover, depletion of endogenous USP26 with short hairpin RNAs significantly suppressed the aerobic glycolysis and proliferation in tumor cells. In mechanism, USP26 was revealed to interact with and stabilize c-Myc, which is a key driver of tumor metabolism and carcinogenesis, via suppressing its polyubiquitination and degradation. In summary, these findings suggest that USP26 plays a novel oncogenic role of USP26 by forming a USP26-c-Myc regulatory axis, and that targeting USP26 may be a potential therapeutic strategy for gastric cancer.

Clear cell renal cell carcinoma (ccRCC) is characterized by Von Hippel Lindau (VHL) gene loss of function mutation, which leads to the accumulation of hypoxia-inducible factor 2α (HIF2α). HIF2α has been well-established as one of the major oncogenic drivers of ccRCC, however, its therapeutic targeting remains a challenge. Through an analysis of proteomic data from ccRCCs and adjacent non-tumor tissues, we herein revealed that Ubiquitin-Specific Peptidase 7 (USP7) was upregulated in tumor tissues, and its depletion by inhibitors or shRNAs caused significant suppression of tumor progression in vitro and in vivo. Mechanistically, USP7 expression is activated by the transcription factors FUBP1 and FUBP3, and it promotes tumor progression mainly by deubiquitinating and stabilizing HIF2α. Moreover, the combination of USP7 inhibitors and afatinib (an ERBB family inhibitor) coordinately induce cell death and tumor suppression. In mechanism, afatinib indirectly inhibits USP7 transcription and accelerates the degradation of HIF2α protein, and the combination of them caused a more profound suppression of HIF2α abundance. These findings reveal a FUBPs-USP7-HIF2α regulatory axis that underlies the progression of ccRCC and provides a rationale for therapeutic targeting of oncogenic HIF2α via combinational treatment of USP7 inhibitor and afatinib.

Reversible protein ubiquitination is a key process for maintaining cellular homeostasis. Deubiquitinases, which can cleave ubiquitin from substrate proteins, have been reported to be deeply involved in disease progression ranging from oncology to neurological diseases. The human genome encodes approximately 100 deubiquitinases, most of which are poorly characterized. One of the well-characterized deubiquitases is ubiquitin-specific protease 29 (USP29), which is often upregulated in pathological tissues and plays important roles in the progression of different diseases. Moreover, several studies have shown that deletion of Usp29 in mice does not cause visible growth and developmental defects, indicating that USP29 may be an ideal therapeutic target. In this review, we provide a comprehensive summary of the important roles and regulatory mechanisms of USP29 in cancer and other diseases, which may help us better understand its biological functions and improve future studies to construct suitable USP29-targeted therapy systems.

Gastric cancer remains a highly prevalent malignancy worldwide with its molecular features poorly understood. To gain full insight into its genetic landscape, we performed whole-transcriptome sequencing on human tumors and adjacent non-tumors to predict the function of microRNA, long coding RNA, circular RNA, and mRNA, as well as estimate their correlation with gastric cancer characteristics through construction of ceRNA, WGCNA and PPI network. Functional enrichment analysis annotated nucleic acid binding, enzyme activity and binding related to differentially expressed miRNAs (dif-miRNAs); energy binding and enzyme binding related to dif-lncRNAs; protein binding and enzyme activity related to dif-circRNAs; protein digestion and absorption related to dif-mRNAs. The expression of key miR-135a-5p, lncRNAs-MSTRG.48856.1, ENST00000569981, MSTRG.22826.1, ENST00000564492, circRNAs-CCSER2, FNDC3B, CORO1C, FAM214A were validated by real-time PCR. The ceRNA network filtered 14 miRNAs, 30 lncRNAs, and 6 mRNA in the lncRNA-ceRNA axis and 8 miRNAs, 9 circRNAs, and 3 mRNA in the circRNA-ceRNA axis. Genes involved in ceRNA were annotated to be closely related to tumor material synthesis and metabolism. The WGCNA network filtered gene clusters related to TNM traits and extracted the hub genes CLDN10, CD177, newGene_35523, newGene_51201, CEACAM7, and newGene_46634. These genes were associated with cell proliferation, metabolism, and enzyme activity regulation. The PPI network analyzed the stable interaction relationships of the hub genes. Our research provides a valuable resource for understanding the molecular mechanisms of gastric cancer from the perspective of tumor metabolism.

Background: Hepatocellular carcinoma (HCC) is a leading cancer worldwide for which diagnosis, treatment and progression are largely unknown. Keratin23 is a potential biomarker forHCC development; however, regulatory mechanisms underlying its expression remain unclear. Inthis research we explored the expression and effect of KRT23 underlying HCC development. Materials and methods: GEPIA was applied to analyze the expression of KRT23 in HCC samples and Kaplan-Merier survival analysis for patients’ prognosis. Next, IHC was further conducted for confirming its expression in HCC tissues. Meanwhile qRT-PCR and western blot analysis were applied to examine the expression of KRT23 on both mRNA and protein level in HCC cell lines compared with immortal hepatocyte LO2. Cell experiments including MTT assay, apoptosis analysis, cell cycle assay and clone formation assay were conducted for cell proliferation while transwell assay and scratch test for metastasis in vitro . Moreover, xenograft tumors in nude mice were further conducted for verification in vivo . As for mechanism in depth, immunofluorescence and western blot were operated to explore the effect of KRT23 on EMT and PI3K/AKT/GSK3βsignaling pathway. Furthermore, Co-immunoprecipitation was applied for interaction between KRT23 and P21. Functional rescue experiments were conducted to further testify their mutual effect. Results: For this research, we discovered the high expression of KRT23 in HCC samples and cell lines. Functionally, KRT23 knockdown reduced cell proliferation and metastasis in vitro and vivo . Furthermore, KRT23 participated in EMT progression and interacted with P21 to mediate PI3K/AKT/GSK3βpathway in HCC development. Conclusion: To summarize, KRT23 accelerated HCC proliferation and metastasis by regulating P21 via PI3K/AKT/GSK3βpathway.

Background Gastric cancer is a highly prevalent cancer type and the underlying molecular mechanisms are not fully understood. Ubiquitin-specific peptidase (USP) 29 has been suggested to regulate cell fate in several types of cancer, but its potential role in gastric carcinogenesis remains unclear. Methods The expression of USP29 in normal and gastric cancer tissues was analyzed by bioinformatics analysis, immunohistochemistry and immunoblot. Gene overexpression, CRISPR-Cas9 technology, RNAi, and Usp29 knockout mice were used to investigate the roles of USP29 in cell culture, xenograft, and benzo[a]pyrene (BaP)-induced gastric carcinogenesis models. We then delineated the underlying mechanisms using mass spectrometry, co-immunoprecipitation (Co-IP), immunoblot, ubiquitination assay, chromatin immunoprecipitation (ChIP), quantitative real-time PCR (qRT-PCR), and luciferase assays. Results In this study, we found that USP29 expression was significantly upregulated in gastric cancers and associated with poor patient survival. Ectopic expression of USP29 promoted, while depletion suppressed the tumor growth in vitro and in vivo mouse model. Mechanistically, transcription factor far upstream element binding protein 1 (FUBP1) directly activates USP29 gene transcription, which then interacts with and stabilizes aurora kinase B (AURKB) by suppressing K48-linked polyubiquitination, constituting a FUBP1-USP29-AURKB regulatory axis that medicates the oncogenic role of USP29. Importantly, systemic knockout of Usp29 in mice not only significantly decreased the BaP-induced carcinogenesis but also suppressed the Aurkb level in forestomach tissues. Conclusions These findings uncovered a novel FUBP1-USP29-AURKB regulatory axis that may play important roles in gastric carcinogenesis and tumor progression, and suggested that USP29 may become a promising drug target for cancer therapy.

BACKGROUND:Endoscopic submucosal dissection (ESD) has been recommended as the first-line treatment for early gastric cancer (EGC). However, poor visualization of the operative field increases both the procedure time and the risk of complications, especially for large and difficult lesions. We introduced a novel technique, magnetic anchor-guided ESD (MAG-ESD) and compared it with conventional ESD (C-ESD) for the treatment of large EGCs in terms of efficacy, safety, and advantages. METHODS:Patients with large EGCs who underwent MAG-ESD or C-ESD at the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to March 2022 were retrospectively enrolled in this study. The patients in the MAG-ESD cohort were matched to those in the C-ESD cohort using propensity score-based matching. The operation time, submucosal dissection time, complete resection status, magnetic anchor, adverse event rate, and tumor recurrence rate were evaluated. RESULTS:Twenty-two patients who underwent MAG-ESD were ultimately matched to those who underwent C-ESD. The median operation time of MAG-ESD and C-ESD was 43 minutes (IQR, 35.2-49.5) and 50.5 minutes (IQR, 42.0-76.0), respectively, among which the submucosal dissection time was 7.6 minutes (IQR, 5.2-10.4) and 14.8 minutes (IQR, 10.8-19.6), respectively. The operation time of MAG-ESD was shorter than that of C-ESD, especially the submucosal dissection time (P < .05). There was a lower incidence of adverse events associated with MAG-ESD (P < .05) when magnetic anchors were successfully placed and retrieved. CONCLUSION:MAG-ESD is feasible, effective, safe, and simple for the treatment of large EGCs at different sites and has a high anchor success rate, which could shorten the operation time and reduce the adverse event rate.

目的 探讨结直肠肿瘤性病变患者内镜黏膜下剥离术(ESD)后息肉样瘢痕结节(PNS)的临床特点.方法 选择行ESD并整块切除、R0切除的结直肠肿瘤性病变患者348例,术后间隔3、6、12个月行结肠镜检查,观察创面愈合情况,出现PNS时需行病理活检检查,比较ESD后PNS患者与正常愈合患者的基本资料.结果 348例患者中有27例(7.76%)出现PNS,均表现为术区原位突出于肠道的息肉样隆起,组织呈红色,质地柔软,病理结果均提示为炎症增生组织,无恶性肿瘤复发或增生不良征象.ESD后PNS患者与正常愈合患者的性别、年龄、原发灶直径、病理类型比较差异均无统计学意义(P均＞0.05),ESD后PNS患者原发部位为左半结肠及直肠的比例高于正常愈合患者(P均＜0.05).27例ESD后PNS患者随访(33.26±15.10)个月,其中随访时间＞36个月14例(51.85%),均未发现PNS发生恶性改变.结论 结直肠肿瘤性病变患者ESD后PNS发生率为7.76%,好发于左半结肠和直肠,病理倾向为良性病变.

[目的]通过对比内镜下微创治疗及外科手术治疗不同直径的胃间质瘤的手术成功率、时间经济成本以及并发症等,分析内镜下切除不同直径的胃间质瘤的有效性及安全性.[方法]收集经病理证实为胃间质瘤且无远处转移的87例患者的临床资料,根据切除方式不同分为内镜组和手术组,每组根据肿瘤直径不同分为r＜2 cm亚组及2 cm≤r≤5 cm亚组.对2组患者的临床特征进行分析,并比较2组在不同肿瘤直径下的手术成功率、手术后的住院时长、住院费用、手术持续时间、术中及术后并发症的严重性及发生率等.[结果]在肿瘤直径r＜2 cm的患者中,内镜组及手术组的胃间质瘤均成功切除且无术中及术后并发症的发生;在肿瘤直径2 cm≤r≤5 cm的患者中,内镜组有1例因为术中出血较多转外科手术治疗,内镜组的手术成功率为94.12％;手术组的手术成功率为100％,但有1例外科手术后因为吻合口发生了瘘再次行手术进行修补;2组的手术成功率和术中及术后并发症的发生率比较差异无统计学意义(P＞0.05).内镜组的手术时间、住院时间及住院费用均小于手术组,2组比较差异有统计学意义(P＜0.05).[结论]对于肿瘤直径r≤5 cm且无远处转移的胃间质瘤,内镜下切除能取得较好的临床效果,具有微创、有效、经济等优势,但是对于病变较大或者浸润较深的胃间质瘤,内镜下切除操作难度大,术前需要严格把握适应证,完善术前超声内镜及腹部CT检查,准确评估胃间质瘤的肿瘤直径及浸润深度,必要时可于手术室完成内镜下治疗.

Objective:To evaluate the feasibility and effectiveness of magnetic anchor-guided endoscopic submucosal dissection (MAG-ESD).Methods:A total of 36 patients with gastrointestinal tumors at different sites who underwent MAG-ESD in the First Affiliated Hospital of Xi'an Jiaotong University from March 2020 to October 2022 were enrolled. The anchor success rate, en bloc resection rate, the anchor time, the procedure time, and the complication incidence were observed and analyzed.Results:Among the 36 patients, there were 9 lesions in stomach, 2 in duodenum, 6 in cecum and 19 in colorectum. Thirty-five (97.2%) patients successfully underwent magnetic anchor, and en bloc resection of lesions were completed. No adverse events such as bleeding or perforation occurred. The anchor time and procedure time was 4.0 (2.0-9.5) min and 36 (16-82) min, respectively.Conclusion:MAG-ESD is feasible and effective for gastrointestinal tumors at different sites, with a high anchor success rate and en bloc resection rate, and shorter operation time, especially for difficult submucosal dissection.

Objective To evaluate the clinical value of capsule endoscope in the diagnosis of unexplained abdominal pain. Methods We made a retrospective analysis of 191 patients with unexplained abdominal pain who sought medical help in our hospital and 25 normal controls. Capsule endoscopy was performed in both groups, small bowel lesions were detected, and clinical data were collected for further analysis. Results The total small bowel lesion detection rate was 52.87%（101/191） in abdominal pain（AP） patients and 20%（5/25） in the control group, respectively. The detection rate of significant findings（ulcers, erosions, polyps, diverticula, parasites, and neoplastic organisms） was only 16.23%（31/191） in AP patients. In the non-significant findings, no statistical difference in the detection rates for vascular malformation, capillary dilation, and lymphoid follicular hyperplasia were found between the two groups, while the detection rate of intestinal lymphangiectasia was significantly higher in the AP patients（23.56% vs. 4%, P＜0.05, OR=7.089）. Conclusion Capsule endoscopy can be an optional choice for diagnosis of unexplained abdominal pain, while the relationship between positive findings and abdominal pain should be further investigated.

目的 探讨hsa_circ_0045943靶向miR-106a对胃癌细胞生物学特性的影响及机制.方法 培养人胃癌细胞MKN-45、AGS和胃黏膜上皮细胞GES-1,real-time PCR检测circ_0045943在胃癌细胞中的表达;构建并转染circ_0045943的过表达和沉默腺病毒载体OE-circRNA和sh-circRNA及阴性对照OE-NC和sh-NC,采用CCK-8法检测AGS细胞在circ_0045943过表达和抑制后的增殖能力变化,TUNEL法检测细胞凋亡,transwell法检测细胞迁移和侵袭,划痕法检测细胞迁移.StarBase数据库筛选circ_0045943和miR-106a的结合位点,real-time PCR检测miR-106a表达;给予OE-circRNA和sh-circRNA,检测circ_0045943表达及miR-106a在circ_0045943过表达和抑制后的表达水平变化.结果 Real-time PCR结果显示,与GES-1相比,circ_0045943在胃癌细胞MKN-45、AGS中表达均降低(P均<0.001);CCK-8显示,OE-circRNA组AGS细胞吸光度值低于sh-circRNA组(P24 h<0.01,P48 h<0.001,P72 h<0.001);TUNE结果显示,过表达circ_0045943时AGS细胞凋亡数增多,沉默circ_0045943时凋亡数减少;transwell结果显示,OE-circRNA组AGS细胞迁移和侵袭数量均低于sh-circRNA组(P均<0.001);划痕实验结果显示,OE-circRNA组AGS细胞迁移率最低,sh-circRNA组迁移率高(P<0.001).Starbase数据库检索circ_0045943和miR-106a具有互补结合序列.Real-time PCR结果显示,miR-106a在胃癌细胞中高表达(P<0.001);OE-circRNA和sh-circRNA处理后circ_0045943和miR-106a表达有统计学差异(P均<0.001),伴随circ_0045943表达的升高和下降,miR-106a表达出现相反变化.结论 circ_0045943在胃癌细胞中低表达,促进或抑制circ_0045943的表达可能通过靶向miR-106a而调控胃癌细胞的增殖、凋亡、迁移和侵袭.

Background Emerging evidence have revealed that circRNAs exert important biological effects in the development and progression of various diseases, including cancer. Our study aimed to elaborated the biological effects of hsa-circ_0003570 in hepatocellular carcinoma (HCC) development at the molecular level. Results The results of functional experiments showed that knockdown of circ_0003570 induced HCC cell growth, migration and invasion, whereas overexpression of circ_0003570 presented the opposite effects. In vivo experiments, xenograft tumors grown from circ-overexpressed cells had smaller tumor volume and weight than the control group. Further investigations suggested that circ_0003570 may function as a competing endogenous RNA via competitively binding miR-182-5p and thereby regulating the repression of downstream target gene STARD13, which were demonstrated by dual luciferase reporter assay and functional rescued experiments. Conclusions Taken together, circ_0003570 suppresses the development of HCC by modulating miR-182-5p/STARD13 axis.

Due to the precise vaporization of the novel 450 nm blue diode laser in soft tissues (i.e., bladder and colon) in our previous studies, porcine stomach tissues were applied here to certify its efficacy in endoscopic mucosal resection (ESR)/endoscopic submucosal dissection (ESD) for hypothetical lesions ex vivo and in vivo.

目的:探讨影响胃间质瘤危险度分级的相关因素,为临床诊断提供参考.方法:回顾性收集2016年01月至2019年12月于我院接受治疗的87例经手术后病理证实为胃间质瘤患者的相关临床资料,分析其临床特征、病理及免疫组化结果、治疗措施等,为临床实践提供重要依据.结果:胃间质瘤患者多为中年人,其平均年龄为(59.10±12.92)岁.首发症状最常见的为腹部不适.通过单因素分析提示患者年龄、肿瘤大小与首发症状有一定程度的相关性.肿瘤生长部位最常见的为胃底,直径以2～5 cm最常见.免疫组化分析可知CD117、DOG-1、CD34阳性率较高,分别为97.70％、97.70％、97.70％,Vim、SMA、Desmin阳性率较低,分别为50.57％、17.24％、5.75％.通过单因素分析提示年龄、SMA表达、Demsin表达、Ki-67标记指数(labeling index,LI)与危险度分级有一定相关性.87例患者中行开腹手术27例,腹腔镜手术25例,双镜联合8例,内镜下治疗27例,11例术后服用甲磺酸伊马替尼进行靶向治疗,外科手术及内镜手术均未出现围手术期治疗相关死亡.结论:胃间质瘤患者首发症状缺乏特异性,但可能与患者年龄、肿瘤大小有一定关系.临床上确诊还需依赖病理及免疫组化结果,必要时可结合患者年龄、SMA表达、Demsin表达、Ki-67 LI进一步判断危险度.

目的 研究青藤碱在胃癌细胞诱导的巨噬细胞极化中的作用及机制.方法 在胃癌细胞BGC-823和MKN-45中加入青藤碱,用CCK-8测定细胞活力,用克隆形成实验测定细胞增殖能力,用共培养和Transwell小室迁移实验评估青藤碱对巨噬细胞的招募和极化,流式细胞术评估巨噬细胞极化,RT-qPCR法和Western blotting分别检测基因RNA水平和蛋白表达水平.结果 青藤碱能抑制胃癌细胞增殖,抑制胃癌细胞对巨噬细胞的募集及抑制其M2型极化作用.青藤碱同时抑制了转录激活因子6(STAT6)的表达和CAAT增强子结合蛋白β(C/EBPβ)的表达和磷酸化.当STAT6过表达时,可以降低青藤碱对胃癌细胞的这些抑制作用.进一步研究发现,STAT6介导胃癌细胞分泌白细胞介素-6(IL-6)是造成青藤碱介导的巨噬细胞募集和M2极化的原因.结论 天然药物青藤碱对胃癌具有良好的肿瘤抑制能力,直接抑制胃癌细胞的生存和迁移,并且通过抑制IL-6的表达,抑制肿瘤微环境中的M2表型,重塑肿瘤环境,降低M2型巨噬细胞为胃癌肿瘤带来免疫抑制环境的风险.

Hematological and neurological expressed 1 (HN1) is closely associated with the proliferation and metastasis of various tumors. However, the physiological functions and clinical significance of HN1 in hepatocellular carcinoma (HCC) remain indistinct. In this study, we investigated the role of HN1 in the pathogenesis of HCC and the underlying mechanism using clinical data from HCC patients, in vitro experiments utilizing HCC cell lines and in vivo animal models. We demonstrated that the overexpressed HN1 in HCC was correlated with patients' adverse outcomes. The gain and loss of function experiments indicated that HN1 could promote the proliferation, migration, and invasion of HCC cells in vitro. Furthermore, we found that HN1 knockdown sensitized HCC cells to oxaliplatin. Mechanically, HN1 prevented HMGB1 protein from ubiquitination and degradation via the autophagy‐lysosome pathway, which was related to the interaction between HN1 protein and TRIM28 protein. In the nucleus, the downregulation of HMGB1 followed by HN1 knockdown resulted in increased DNA damage and cell death in the oxaliplatin‐treated HCC cells. In the cytoplasm, HN1 regulated autophagy via HMGB1. Furthermore, HN1 knockdown in combination with HMGB1 overexpression restored the aggressive phenotypes of HCC cells and the sensitivity of these cells to oxaliplatin. HN1 knockdown inhibited the tumor growth and metastasis, and promoted the anticancer efficiency of oxaliplatin in vivo. In conclusion, our data suggest that the HN1/HMGB1 axis plays an important role in the development/progression and chemotherapy of HCC. Our findings indicate that the HN1/HMGB1 axis may be a promising therapeutic target for HCC treatment.