To evaluate the efficacy and safety of biological mesh in laparoscopic inguinal hernia repair. A retrospective analysis was conducted on 200 patients who underwent laparoscopic transabdominal preperitoneal repair (TAPP) between March 2019 and March 2022. Patients were divided into Group A (n = 100), repaired with acellular matrix biological mesh, and Group B (n = 100), repaired with polypropylene mesh. Follow-ups were performed at 1, 3, 6 months, 1 year, and 3 years postoperatively. Outcome measures included operation time, intraoperative blood loss, postoperative hospital stay, recurrence, infection, seroma, foreign body sensation, and chronic pain. No significant differences were observed between the two groups in operation time, intraoperative blood loss, postoperative hospital stay, recurrence, infection, seroma, or chronic pain (P > 0.05). However, the incidence of foreign body sensation was significantly lower in the Group A (P < 0.05). The acellular matrix biological mesh is safe and effective in the treatment of inguinal hernia, and can reduce the incidence of postoperative foreign body sensation at the same time, providing a new choice for laparoscopic inguinal hernia repair.

​To compare the short-term outcomes of laparoscopic transabdominal preperitoneal repair (TAPP) and laparoscopic intraperitoneal onlay mesh (IPOM Plus) repair for umbilical hernia. A retrospective analysis was conducted on 55 patients with umbilical hernia treated at the Second Affiliated Hospital of Xi’an Jiaotong University from July 2023 to March 2025. The patients were divided into two groups based on the surgical approach: the TAPP group (experimental group, n=30) and the IPOM Plus group (control group, n=25). Operation time, intraoperative blood loss, postoperative hospital stay, hernia recurrence, surgical site/mesh infection, seroma, foreign body sensation, postoperative pain, bowel obstruction and perforation were compared. Follow-ups were performed at 1, 3 and 6 months postoperatively. There were no statistically significant differences between the two groups regarding baseline characteristics, intraoperative blood loss, postoperative hospital stay, recurrence rate, surgical site/mesh infection rate, seroma formation, bowel obstruction and perforation. However, the TAPP group demonstrated a longer operative time (P<0.05), while showing significantly lower postoperative pain scores and reduced incidence of foreign body sensation (P<0.05). TAPP can significantly improve the patient's postoperative recovery experience. Although it prolongs operative time, its safety and short-term efficacy are comparable to IPOM Plus, providing an alternative surgical option for umbilical hernia repair. Further large-scale studies with long-term follow-up are needed to validate these advantages and establish TAPP as a routine surgical option for umbilical hernia.

RNA N6-methyladenosine (m6A) is a common RNA modification in eukaryotes, and its abnormal regulation is closely related to cancer progression. Aerobic glycolysis is a main way for cancer cells to obtain energy. It was found that beaded filament structural protein 1 (BFSP1) is a m6A related gene in liver cancer. However, the effect of m6A-modified BFSP1 on aerobic glycolysis and how it is regulated in liver cancer progression have not been explored. Here, we found that BFSP1 was upregulated in liver cancer cells and tissues. Overexpression of BFSP1 promoted the viability, invasion, and aerobic glycolysis of liver cancer cells, whereas knockdown of BFSP1 showed the opposite effects. Co-immunoprecipitation, immunofluorescence and GST pull down analyses showed that BFSP1 directly interacted with tropomodalin 4 (TMOD4), and knockdown of TMOD4 reversed BFSP1 overexpression-induced malignant phenotypes and aerobic glycolysis in liver cancer cells. Moreover, methyltransferase-like 3 (METTL3) enhanced BFSP1 stability by augmenting m6A modification of BFSP1 mRNA, which is achieved in a YTHDF1-dependent manner. In vivo experiments in mice confirmed that METTL3 increased BFSP1 stability by promoting m6A modification of BFSP1 mRNA, and knockdown of BFSP1 inhibited tumor growth and metastasis. In summary, METTL3-mediated m6A methylation of BFSP1 mRNA plays an important role in the aerobic glycolysis and progression of liver cancer, providing a potential therapeutic strategy for liver cancer.

The N6-methyladenosine (m6A) methylase WTAP has been identified as a proto-oncogene in multiple cancers, including hepatocellular carcinoma (HCC). Interestingly, although WTAP expression does not differ between normal liver and HCC tissues or across different stages of HCC, patients with higher WTAP expression exhibit significantly shorter median survival times (MSTs). Here, we found that WTAP was upregulated in tumor-infiltrating CD8+ T cells, which were more enriched in HCC patients compared to the controls. HCC patients also displayed higher PD1 levels and a greater proportion of exhausted CD8+ T cells (TCF+ PD1+). Moreover, WTAP promoted PD1 expression and suppressed the proliferation and immune activity of CD8+ T cells. In the co-culture system, WTAP-overexpressing CD8+ T cells enhanced the malignancy of HCC cells. Notably, WTAP silencing further augmented the boosting effect of PD1 silencing on CD8+ T cell immune activity and strengthened its inhibitory effect on HCC cell growth. As an m6A "writer", WTAP increased the m6A level of PD1 mRNA, thereby promoting YTHDF1-mediated translation of PD1. Finally, in the HuNSG xenograft tumor model, WTAP knockdown not only alleviated CD8+ T cell exhaustion and inhibited tumor progression but also synergistically enhanced the antitumor efficacy of anti-PD1 therapy. In conclusion, WTAP promoted CD8+ T cell exhaustion and HCC progression by facilitating the m6A modification and translation of PD1 mRNA.

Objective To explore the relationship between serum Krüppel-like factor 5(KLF5) and actinin-4 with prognosis of hepatocellular carcinoma (HCC) treated with transcatheter arterial chemoembolization (TACE). Methods From March 2015 to March 2020, 130 HCC patients admitted into the Second Affiliated Hospital were collected as study subjects and divided into HCC group and 86 patients with liver cirrhosis were collected as control group. After 3 years of postoperative follow-up, HCC patients were sub-divided into survival group (n=38) and mortality group (n=92) based on their survival outcomes. ELISA was applied to detect the level of serum KLF5 and actinin-4 in each group and analyzed the correlation between serum KLF5 and actinin-4 levels. Cox regression was applied to analyze the risk factors affecting the prognostic mortality of HCC patients; Receiver operating characteristic curve(ROC) was plotted to evaluate the predictive value of serum KLF5 and actinin-4 levels for the prognostic mortality of HCC patients. Results The serum level of KLF5 and actinin-4 in the mortality group was significantly higher than those in the survival group(P＜0.05); There was a positive correlation between serum level of KLF5 and actinin-4 in HCC patients(P＜0.001); Low differentiation, staging (CNLC) stage IIIa of China liver cancer staging (CNLC), vascular invasion and elevated level of KLF5 and actinin-4 were risk factors for prognostic mortality in HCC patients(P＜0.05); The area under the curve (AUC) of serum KLF5 and actinin-4 alone and in combination for predicting mortality in HCC patients was 0.835, 0.866, and 0.936, respectively, showing a high level of combined predicting function (Zcombination-KLF5=2.792, P=0.005, Zcombination-actinin-4=2.014, P=0.044). Conclusions Serum level of KLF5 and actinin-4 l found in HCC patients has a high predictive value for prognosis.

Dysregulation of cholesterol metabolism is an important feature of cancer development. There are limited reports on the involvement of lncRNAs in hepatocellular carcinoma (HCC) progression via the cholesterol metabolism pathway. The present study explored the effect of LINC00618 on HCC growth and metastasis, and elucidated the underlying mechanisms involved in cholesterol metabolism. Here, we found that LINC00618 expression was upregulated in cancerous tissues from 30 patients with HCC compared to that in adjacent normal tissues. High expression of LINC00618 was detected in metastatic HCC tissues. LINC00618 is predominantly localized in the nucleus and overexpression of LINC00618 facilitated HCC cell proliferation, migration and EMT progression by promoting cholesterol biosynthesis. Mechanistically, the 1-101nt region of LINC00618 bound to NSUN2. LINC00618 inhibited ubiquitin-proteasome pathway-induced NSUN2 degradation. NSUN2 stabilized by LINC00618 increased m5C modification of SREBP2 and promoted SREBP2 mRNA stability in a YBX1-dependent manner, thereby promoting cholesterol biosynthesis in HCC cells. Moreover, mouse HCC xenograft and lung metastasis models were established by subcutaneous and tail vein injections of MHCC97 cells transfected with or without sh-LINC00618. Silencing LINC00618 impeded HCC growth and metastasis. In conclusion, LINC00618 promoted HCC growth and metastasis by elevating cholesterol synthesis by stabilizing NSUN2 to enhance SREBP2 mRNA stability in an m5C-dependent manner.

Abstract Background The tumor development is related to disruption of circadian rhythms. However, the causal relationship between chronotype and intrahepatic cholangiocarcinoma (ICC) and molecular mechanism of chronotype-related genes (CRGs) are vague. Methods Genetic summary statistics were obtained from the Integrative Epidemiology Unit (IEU) OpenGWAS and genome-wide association studies (GWAS) Catalog. Univariate Mendelian randomization (MR) analysis and sensitivity analysis were then performed. Subsequently, the CRGs were obtained based on the single nucleotide polymorphisms (SNPs) of chronotype for differential expression analysis between disease and control groups based on University of California, Santa Cruz (UCSC) Xena database, and the identification of hub genes via STRING database and immune infiltration analysis. Finally, the single-cell transcriptome dataset GSE138709 downloaded from Gene Expression Omnibus (GEO) database was used to analyze the relationship between hub genes and annotated cell types. The functional enrichment analysis, pseudotime analysis and cell communication analysis were also explored. Results The MR results revealed that chronotype was a protective factor causally related to ICC, and the reliability was illustrated by the sensitivity analysis. A total of 180 differentially expressed CRGs were acquired, including 101 up-regulated and 79 down-regulated in ICC. Of which, four genes were marked as hub genes based on protein-protein interaction network, namely IDH1, PEX13, DECR2 and PEX12. Moreover, a total of ten cell types were annotated in GSE138709, including T cells, malignant cells, macrophages, NK cells, dendritic cells, B cells, endothelial cells, cholangiocytes, hepatocytes and fibroblasts. Thereinto, NK cells and hepatocytes as key cells were remarkably discrepant between ICC and control samples. The expression of DECR2 and IDH1 in hepatocytes was higher in control group than in ICC group. Furthermore, hepatocytes might transform into cholangiocytes and malignant cells, and both hepatocytes and NK cells interacted strongly with macrophages. Conclusion Our study supported a causal relationship between chronotype and ICC, and provided the theoretical basis and reference value for research on MR.

Aerobic glycolysis plays an important role in multidrug resistance of cancer cells. Here, we screened different expressed lncRNAs associated with sorafenib resistance of liver cancer cells, by intersecting the bioinformatics analyses of TCGA and GEO (the GSE62813 dataset) databases. Our results revealed that the 18 upregulated lncRNAs in the intersection are associated with and enriched in metabolism of small molecule organic acids, suggesting their potential in glycolysis. The lncRNA small nucleolar RNA host gene 1 (Snhg1) was chosen as a potential regulator of aerobic glycolysis in liver cancer cells, for its significant promotion on lactate production. Gain- and loss-of-function experiments mediated by Crispr-Cas9 technique in HepG2 cells indicated that Snhg1 promoted cell proliferation, invasion, sorafenib resistance, and aerobic glycolysis. In the mechanism exploration, we found that Snhg1 can interact with SND1 protein, a famous RNA binding protein and recently identified "Reader" of N6-methyladenosine (m6A). SND1 was demonstrated to be positively regulated by Snhg1 and had similar promoting effects on proliferation, invasion, sorafenib resistance, and aerobic glycolysis of HepG2 cells. SND1 bound with and promoted the expression of SLC7A11, an aerobic glycolysis regulator. Furthermore, either silencing SLC7A11 or blocking aerobic glycolysis with 2-deoxy-d-glucose (2-DG) was able to reverse the promotion of Snhg1 overexpression on malignancy, sorafenib resistance, and aerobic glycolysis of HepG2 cells. Finally, in a liver cancer xenograft mouse model, we found that formed tumors with Snhg1-knocked-down HepG2 cells were more sensitive to sorafenib administration. Altogether, SNHG1 contributes to sorafenib resistance of liver cancer cells by promoting SND1-m6A-SLC7A11-mediated aerobic glycolysis.

Hepatic ischemia-reperfusion (IR) injury is a complex systemic process causing a series clinical problem. C/EBP alpha is a key transcription factor for hepatocyte function, but its role and mechanism in regulating hepatic IR injury are largely unknown. Occluding portal vein and hepatic artery was used to establish a mouse model of hepatic IR injury. C/EBP alpha expression was decreased in IR-injured liver compared with the sham, accompanied by increased contents of serum alanine transaminase (ALT), aspartate transaminase (AST), high mobility group box-1, and proportion of hepatic cells. Oxygen and glucose deprivation/recovery (OGD/R) was used to establish a cellular hepatic IR model in WRL-68 hepatocytes in vitro, and C/EBP alpha was overexpressed in the hepatocytes to evaluate its effect on hepatic IR injury. OGD/R promoted oxidative stress, cell apoptosis and endoplasmic reticulum (ER) stress in hepatocytes, which was reversed by C/EBP alpha overexpression. Then, we found that C/EBP alpha promoted histone deacetylase 1 (HDAC1) transcription through binding to HDAC1 promoter. Moreover, HDAC1 deacetylated the activating transcription factor 4 (ATF4), a key positive regulator of ER stress. Trichostatin-A (an HDAC inhibitor) or ATF4 overexpression reversed the improvement of C/EBP alpha on OGD/R-induced ER stress and hepatocyte dysfunction. 4-Phenylbutyric acid (an endoplasmic reticulum stress inhibitor) also reversed the hepatic IR injury induced by ATF4 overexpression. Finally, lentivirus-mediated C/EBP alpha overexpression vector was applied to administrate hepatic IR mice, and the results showed that C/EBP alpha overexpression ameliorated IR-induced hepatic injury, manifesting with reduced ALT/AST, oxidative stress and ER stress. Altogether, our findings suggested that C/EBP alpha ameliorated hepatic IR injury by inhibiting ER stress via HDAC1-mediated deacetylation of ATF4 promoter.

Lysyl-oxidase-like 3 (LOXL3) was reported to be essential in epithelial-mesenchymal transition (EMT) of cancers. However, the role of LOXL3 in hepatocellular carcinoma (HCC) remained unclear. In this study, we explored clinical significance, biological functions, and regulatory mechanisms of LOXL3 in HCC. Our study found that LOXL3 expression was markedly associated with the tumor size and clinical stage of HCC, and it was highly expressed in tumor tissues of metastatic HCC patients. High expression of LOXL3 predicted a poor prognosis of HCC. TGF-β1 treatment elevated LOXL3 protein expression and cell invasion, and reduced cell apoptosis in HCC cell lines (SMMC-7721 and Huh-7), while downregulation of LOXL3 reversed the promotive effects of TGF-β1 treatment on LOXL3 protein expression and cell invasion, and the inhibitory effect on cell apoptosis. Mechanistically, LOXL3 interacted with snail family transcriptional repressor 1 (Snail1) through STRING database and RIP assay, and Snail1 bound to ubiquitin-specific peptidase 4 (USP4) promoter by JASPAR database, luciferase reporter gene and Co-IP assays. Overexpression of USP4 reversed the inhibitory effect of LOXL3 silence on EMT in HCC cells through deubiquitinating and stabilizing the expression of Snail1. Moreover, LOXL3-promoted HCC EMT through Wnt/β-catenin/Snail1 signaling pathway. In vivo study revealed that silence of LOXL3-inhibited HCC tumor growth. In conclusion, LOXL3 silence inhibited HCC invasion and EMT through Snail1/USP4-mediated circulation loop and Wnt/β-catenin signaling pathway.

Objective: The treatment and prognosis of patients with advanced colorectal cancer (CRC) remain a difficult problem. Herein, we investigated the role of DEAD (Asp-Glu-Ala-Asp) box helicase 3 (DDX3) in CRC and proposed potential therapeutic targets for advanced CRC. Methods: The expression of DDX3 in CRC and its effect on prognosis were explored by databases and CRC tissue microarrays. Stable DDX3 knockdown and overexpression cell lines were established with lentiviral vectors. The effects of DDX3 on CRC were investigated by functional experiments in vitro and in vivo. The molecular mechanism of DDX3 in CRC was explored by western blotting. Molecular-specific inhibitors were further used to explore potential therapeutic targets for advanced CRC. Results: The expression of DDX3 was decreased in advanced CRC, and patients with low DDX3 expression had a poor prognosis. In vitro and in vivo experiments showed that low DDX3 expression promoted the proliferation, migration and invasion of CRC. DDX3 loss regulated E-cadherin and β-catenin signaling through the mitogen-activated protein kinase (MAPK) pathway as shown by western blotting. In addition, the MEK inhibitor, PD98059, significantly reduced the increased cell proliferation, migration and invasion caused by knockdown of DDX3. Conclusions: DDX3 acts as a tumor suppressor gene in CRC. DDX3 loss in advanced cancer promotes cancer progression by regulating E-cadherin and β-catenin signaling through the MAPK pathway, and targeting the MAPK pathway may be a therapeutic approach for advanced CRC.

Background: Circular RNAs (circRNAs) serve as critical regulatory factors in cancer development. Nonetheless, the potential regulatory mechanism of circRNA sorting nexin 27 (circ_SNX27) in hepatocellular carcinoma (HCC) is still unknown. Methods: The circ_SNX27, microRNA-637 (miR-637), and fibroblast growth factor receptor 1 (FGFR1) levels were quantified by quantitative real-time polymerase chain reaction and western blot analysis. Next, function experiments were conducted using in vitro assays and in vivo senograft study. The relationship between miR-637 with circ_SNX27 or FGFR1 was uncovered by dual-luciferase reporter and RNA pull-down assays. Results: The circ_SNX27 and FGFR1 levels were up-regulated, but miR-637 content was reduced in HCC. Circ_SNX27 down-regulation inhibited HCC cell proliferation, motility, and invasion and promoted apoptosis in vitro, as well as weakened tumor growth in vivo. Circ_SNX27 served as a sponge of miR-637 to promote FGFR1 expression. MiR-637 reduction abolished the restrained effect of circ_SNX27 absence on HCC cell development. Moreover, miR-637 curbed HCC cell malignant phenotype by regulating FGFR1. Conclusion: Circ_SNX27 contributed to HCC development via miR-637/FGFR1 axis, offering a new idea for the treatment of HCC.

[This corrects the article on p. 1764 in vol. 12, PMID: 31933995.].

目的:探讨lncRNA CEBPA-AS1对胃癌细胞生物学行为的影响及其可能作用机制.方法:qRT-PCR法检测胃癌组织、癌旁组织与正常人胃上皮GES1细胞和人胃癌SNU-1、AGS、HS-746T细胞系中lncRNA CEBPA-AS1、miR-455-3p的表达量.si-NC、si-lncRNA CEBPA-AS1、miR-NC、miR-455-3p mimics、si-lncRNA CEBPA-AS1与anti-miR-NC、si-lncRNA CEBPA-AS1与an-ti-miR-455-3p分别转染至SNU-1细胞(分别命名为si-NC组、si-lncRNA CEBPA-AS1组、miR-NC组、miR-455-3p组、si-lncRNA CEBPA-ASl +anti-miR-NC组和si-lncRNA CEBPA-ASl +anti-miR-455-3p组)后,MTT实验与平板克隆形成实验分别检测细胞增殖及克隆形成能力,Transwell小室实验检测细胞迁移及侵袭能力,双荧光素酶报告基因实验与qRT-PCR实验验证lncRNA CEB-PA-AS1与miR-455-3p的靶向调控关系,Western blot法检测MMP2、MMP9蛋白表达情况.结果:与癌旁组织比较,胃癌组织中lncRNA CEBPA-AS1的表达量显著升高,miR-455-3p的表达量显著降低,差异均有统计学意义(均P＜0.05).与GES1细胞比较,SNU-1、AGS、HS-746T细胞中lncRNA CEBPA-ASl的表达量显著升高,miR-455-3p的表达量显著降低,其中SNU-1细胞的lncR-NA CEBPA-AS1表达量最高,差异均有统计学意义(均P＜0.05).与si-NC组比较,si-lncRNA CEBPA-AS1组细胞活力降低,细胞克隆形成数、迁移及侵袭细胞数减少,MMP2、MMP9蛋白表达水平降低,差异均有统计学意义(P＜0.05).与miR-NC组比较,miR-455-3p组细胞活力降低,细胞克隆形成数、迁移及侵袭细胞数减少,MMP2、MMP9蛋白表达水平降低,差异均有统计学意义(P＜0.05).lncRNA CEBPA-AS1可靶向结合miR-455-3p,并可负调控miR-455-3p的表达.与si-lncRNA CEBPA-AS l+an-ti-miR-NC组比较,si-lncRNA CEBPA-AS l+anti-miR-455-3p组细胞活力升高,细胞克隆形成数、迁移及侵袭细胞数增多,MMP2、MMP9蛋白表达水平升高,差异均有统计学意义(P＜0.05).结论:干扰lncRNA CEBPA-AS1表达可通过靶向调控miR-455-3p而抑制胃癌细胞增殖、克隆形成、迁移及侵袭.

目的 探讨circPTPRA与miR-1252在胃癌中的表达及其对胃癌细胞生物学行为的影响.方法 取术中切除的胃癌组织与癌旁组织(距癌组织>5 cm处的组织)进行实验,随后采用qRT-PCR检测胃癌组织、癌旁组织中circPTPRA与miR1252的表达情况.体外培养人胃癌细胞HGC-27,分别转染pcDNA、pcDNA-circPTPRA、si-NC、si-circPTPRA、anti-miR-NC、antimiR-1252、共转染pcDNA-circPTPRA和miR-NC、共转染pcDNA-circPTPRA和miR-1252 mimics.CCK-8实验检测细胞增殖;流式细胞仪检测细胞周期;Transwell小室实验检测细胞迁移,Transwell Matrigel体外侵袭实验检测细胞侵袭;双荧光素酶报告基因实验检测circPTPRA与miR-1252的靶向关系;Western blot检测MMP-2、MMP-9蛋白表达量.结果 与癌旁组织比较,胃癌组织中circPTPRA的表达量显著降低(P<0.05),miR-1252的表达量显著升高(P<0.05).与转染pcDNA组比较,转染pcDNA-circPTPRA组细胞活力显著降低,G0/G1期细胞比例显著升高,S期细胞比例显著降低,细胞迁移数及侵袭数显著减少,MMP-2、MMP-9蛋白的表达水平显著降低,差异均有统计学意义(P<0.05).circPTPRA能够靶向结合miR-1252;转染pcDNAcircPTPRA组miR-1252的相对表达量显著降低(P<0.05);转染si-circPTPRA组miR-1252的相对表达量显著升高(P<0.05).与转染anti-miR-NC组比较,转染anti-miR-1252组细胞活力显著降低,G0/G1期细胞比例显著升高,S期细胞比例显著降低,细胞迁移及侵袭数显著减少,MMP-2、MMP-9蛋白表达水平显著降低,差异均有统计学意义(P<0.05).与共转染pcDNAcircPTPRA和miR-NC组比较,共转染pcDNA-circPTPRA和miR-1252 mimics组细胞活力显著升高,G0/G1期细胞比例显著降低,S期细胞比例显著升高,迁移及侵袭细胞数显著增多,MMP-2、MMP-9蛋白表达水平显著升高,差异均有统计学意义(P<0.05).结论 circPTPRA过表达可通过负向调控miR-1252而抑制胃癌细胞增殖、迁移、侵袭及诱导细胞周期阻滞.

目的 探讨环状RNA PUM1(circPUM1)对结肠癌细胞增殖、凋亡、迁移、侵袭的影响及其分子机制.方法 实时荧光定量聚合酶链反应(qRT-PCR)检测结肠癌组织、癌旁组织中circPUM1、微小RNA-524-5p(miR-524-5p)的表达量.体外培养人结肠癌细胞株SW620,分别将si-NC、si-circPUM1、miR-NC、miR-524-5p mimics、si-circPUM1与anti-miR-NC、si-circPUM1与anti-miR-524-5p转染至SW620细胞.甲基噻唑基四唑(MTT)检测细胞增殖;Transwell小室实验检测细胞迁移、侵袭能力;流式细胞术检测细胞凋亡率;双荧光素酶报告实验验证circPUM1是否能够结合miR-524-5p;蛋白免疫印迹法(Western blotting)检测细胞周期蛋白1(Cyclin D1)、p21、基质金属蛋白酶-2(MMP-2)、基质金属蛋白酶-9(MMP-9)、B淋巴细胞瘤-2(Bcl-2)、B淋巴细胞瘤-2相关蛋白(Bax)表达量.结果 结肠癌组织circPUM1的表达水平显著高于癌旁组织(P＜0.05),miR-524-5p的表达水平显著降低(P＜0.05);干扰circPUM1表达或miR-524-5p过表达后,细胞活力显著降低(P＜0.05),迁移细胞数与侵袭细胞数显著减少(P＜0.05),细胞凋亡率显著升高(P＜0.05),Cyclin D1、MMP-2、MMP-9、Bcl-2蛋白表达显著降低(P＜0.05),p21、Bax蛋白表达显著升高(P＜0.05);双荧光素酶报告实验证实circPUM1可靶向结合miR-524-5p的作用位点;抑制miR-524-5p表达可减弱干扰circPUM1表达对SW620细胞增殖、凋亡、迁移、侵袭的作用.结论 circPUM1可通过海绵吸附miR-524-5p促进结肠癌细胞增殖、迁移、侵袭,抑制细胞凋亡.

X-linked ectodermal dysplasia receptor (XEDAR) is a new member of the tumor necrosis factor receptor (TNFR) family that induces cell death. The purpose of this study is to determine the tumor-suppressive potential of XEDAR in the development and differentiation of gastric cancer (GC). XEDAR levels were analyzed in human GC tissues and adjacent normal tissues by immunohistochemistry (IHC), quantitative real-time reverse transcription PCR (RT-qPCR), and Western blot analysis. We found that XEDAR expression was significantly downregulated in GC tissues and further decreased in low differentiated GC tissues. Overexpression of XEDAR in MKN45 and MGC803 cells suppressed the ability of cell proliferation and migration, whereas silencing XEDAR showed the opposite effect. Additionally, XEDAR silencing resulted in the upregulation of the differentiation molecular markers β-catenin, CD44 and Cyclin D1 at the protein levels, whereas XEDAR overexpression showed the opposite effect. Notably, XEDAR positively regulated the expression of liver X receptor alpha (LXRα) through upregulating the RELA gene that was characterized as a transcription factor of LXRα in this study. Inhibition of LXRα by GSK2033 or activation of the Wnt/β-catenin pathway by Wnt agonist 1 impaired the effect of XEDAR overexpression on differentiation of MKN45 cells. Moreover, inhibition of RELA mediated by siRNA could promote cell proliferation/migration and rescue the effect of XEDAR overexpression on cell behaviors and expression of genes. Subsequently, overexpression of XEDAR suppressed the growth of GC cells in vivo . Taken together, our findings showed that XEDAR could promote differentiation and suppress proliferation and invasion of GC cells.

Objective:To investigate the effect of stilamin on mitochondrial injury of acute pancreatitis (AP)-related acinar cells and the possible mechanism.Methods:24 C57BL/6 mice were randomly divided into control group, AP group and AP+ stilamin treatment group (Stilamin group). AP model was prepared by intraperitoneal injection of l-arginine in AP group, 0.4 mg/kg stilamin was intraperitoneally injected at 2 h after modeling in stilamin group, and control group received intraperitoneal injection with saline in the same volume. Histopathological examination of pancreatic tissue was performed routinely. Serum levels of IL-6, IL-10 and TNF- α were detected by ELISA, serum levels of amylase and lipase, and serum levels of superoxide dismutase (SOD), malondialdehyde (MDA) and glutathione (GSH) reflecting oxidative stress were detected by biochemistry method, respectively. Mitotracker red fluorescent labeling was used to detect the number of mitochondria in pancreatic acinar cells, and western blot was used to detect the ND-3 protein expression reflecting the number of mitochondria. The expression levels of mitochondrial fusion protein (Mfn-2) and mitochondrial transcription factor A (TFAM) reflecting mitochondrial function were determined by immunohistochemical staining.Results:Compared with AP group, the pancreatic pathology scores of mice in Stilamin group were significantly decreased [(2.07±0.50) vs (3.93±0.64)], serum amylase and lipase levels were significantly decreased [(1 493±172)U/L vs (1 832±86)U/L, (225.4±83.2)U/L vs (671.0±164.5)U/L]; serum IL-6 and TNF-α levels were greatly decreased, while IL-10 levels were obviously increased [(99.09±39.65)ng/L vs (358.60±139.22)ng/L, (22.75±11.24)ng/L vs (40.83±1.62)ng/L, (15.12±5.03)ng/L vs (9.92±8.73)ng/L]. Mitotracker staining density and expression levels of ND-3, Mfn-2 and Tfam were increased [(71.67±17.62) vs (40.00±10.15), (0.45±0.16) vs (0.11±0.05), 78% vs 54%, 86% vs 47%], and MDA, SOD, and GSH levels were increased [(5.00±1.73)nmol/mg vs (7.33±2.08)nmol/mg protein, (17.33±3.21)U/mg vs (8.67±2.07)] U/mg protein. The ratio of (131.33±20.55)U/mg to (77.33±29.69)U/mg protein was statistically significant (all P<0.05). Conclusions:By protecting the mitochondria number and function of damaged pancreatic acinar cells and reducing the level of oxidative stress, stilamin could alleviate the level of pancreatic tissue damage and inflammatory response in mice with acute pancreatitis.

[目的]研究FAT4通过上调乳腺癌耐药蛋白(BCRP)影响结直肠癌对5-FU的耐药性.[方法]采用RT-PCR检测50例结直肠癌患者中癌组织以及相应癌旁组织和正常组织中FAT4表达量;采用免疫组化检测手术组以及手术+新辅助化疗组中FAT4以及BCRP的相对表达量,并采用Pearson相关性分析FAT4与BCRP表达水平间的相关性;采用RT-PCR检测各结直肠癌细胞系(SW48、HT-29、HCT-116、SW620、DLD1、SW480、CaCO2、LOVO)中FAT4和BCRP mRNA的表达量;构建过表达FAT4或敲降FAT4的直肠癌细胞系,用RT-PCR以及Western blot检测FAT4表达水平的变化;进一步使用5-FU刺激过表达FAT4或敲降FAT4的直肠癌细胞系,MTT检测其增殖能力的变化.[结果]与正常组织以及癌旁组织比较,FAT4以及BCRP在癌组织中表达量较高(P＜0.001),5-FU刺激结直肠癌细胞后,与对照组比较,FAT4过表达可以增加其细胞增殖能力(P＜0.01),FAT4敲减可以降低细胞增殖能力(P＜0.01).Pearson相关性分析显示,结直肠癌患者中FAT4和BCRP表达水平存在明显的正相关(P＜0.001).在HT-29细胞中FAT4过表达能促进BRCP的表达,在SW480细胞中FAT4敲减后会抑制BRCP的表达;在过表达FAT4的结直肠癌细胞中转染shBCRP会降低其对5-FU的耐药性.[结论]FAT4通过上调耐药基因BCRP,使直肠癌细胞对5-FU的耐药性增加.