氧化低密度脂蛋白、血清可溶性凝集素样氧化低密度脂蛋白受体-1与痛风患者亚临床动脉粥样硬化的关系

目的 分析痛风患者血清可溶性凝集素样氧化低密度脂蛋白受体-1(sLOX-1)和氧化低密度脂蛋白(ox-LDL)的变化及其与患者亚临床动脉粥样硬化(AS)的关系。方法 选择68例痛风患者和43例体检健康者(对照组)作为研究对象,根据双侧颈动脉内中膜厚度(IMT)和有无动脉斑块形成,将痛风患者分为亚临床AS组(AS组,38例)和非亚临床AS组(non-AS组,30例)。用酶联免疫吸附试验测定血清sLOX-1和ox-LDL水平,记录痛风患者病程、体质量指数(BMI)、血尿酸(UA)、血脂、空腹血糖、糖化血红蛋白(HbA1c)、胰岛素抵抗指数(HOMA-IR)和超敏C反应蛋白(hs-CRP)等临床资料。分析痛风患者血清ox-LDL和sLOX-1的相关性。采用受试者工作特征(ROC)曲线及曲线下面积(AUC)评价ox-LDL和sLOX-1水平对痛风合并亚临床AS的诊断价值。采用多因素Logisitic回归分析痛风患者合并亚临床AS的相关危险因素。结果 AS组患者血清ox-LDL[42.37(20.77,181.20)ng/mL]与sLOX-1[7.66(4.43,14.03)ng/mL]水平均高于non-AS组[oxLDL:19.03(8.46,32.44)ng/mL,sLOX-1:5.70(2.41,10.87)ng/mL],non-AS组ox-LDL和sLOX-1水平高于对照组[ox-LDL:10.71(4.22,14.74)ng/mL,sLOX-1:0.98(0.49,3.18)ng/mL],差异均有统计学意义(P<0.05);痛风患者血清ox-LDL水平与sLOX-1水平呈正相关(r=0.531,P<0.001);ox-LDL诊断痛风患者合并亚临AS的AUC为0.718,sLOX-1诊断痛风患者合并亚临床AS的AUC为0.769。多因素Logistic回归分析显示,年龄、病程、三酰甘油、低密度脂蛋白胆固醇、HOMA-IR、ox-LDL是痛风患者合并亚临床AS的影响因素。结论 痛风患者血清ox-LDL、sLOX-1表达增加与患者亚临床AS的发生密切相关,二者的临床检测对痛风合并AS的早期诊断有意义。

类风湿关节炎患者血清基质金属蛋白酶-9及细胞外基质金属蛋白酶诱导因子水平与颈动脉粥样硬化的相关性研究

目的研究类风湿关节炎(RA)患者血清基质金属蛋白酶-9(MMP-9)及细胞外基质金属蛋白酶诱导因子(EMMPRIN)的变化,探讨其与RA发生颈动脉粥样硬化的相关性。方法通过高分辨超声检测颈动脉内中膜厚度(IMT)和有无动脉斑块形成,将75例RA患者分为合并颈动脉粥样硬化组(RA-AS组,44例)和非颈动脉粥样硬化组(RA-nonAS组,31例)和32例健康体检正常者(对照组)作为研究对象。采用ELISA法测定3组血清MMP-9和EMMPRIN水平,记录RA患者病程、体质指数(BMI)、类风湿关节炎疾病活动评分(DAS28)、类风湿因子(RF)、血脂、空腹血糖、糖化血红蛋白(GHbA1c)、血沉(ESR)、超敏C反应蛋白(hs-CRP)、胰岛素抵抗指数(HOMA-IR)等临床资料。Spearman相关性研究分析MMP-9与EMMPRIN的关系。用受试者工作特征曲线(ROC)及曲线下面积(AUC)评价血清MMP-9和EMMPRIN水平对RA合并颈动脉粥样硬化的诊断价值。采用Logisitic回归分析RA合并颈动脉粥样硬化的影响因素。结果RA-AS组患者血清MMP-9[47.25(27.52,66.36)ng/mL]与EMMPRIN[5.49(3.26,7.56)ng/mL]水平均显著高于RA-nonAS组[MMP-9:19.36(11.50,27.98)ng/mL,EMMPRIN:3.279(2.44,4.47)ng/mL],non-AS组MMP-9和EMMPRIN水平显著高于对照组[MMP-9:7.89(5.32,14.38)ng/mL,EMMPRIN:2.643(1.69,4.37)ng/mL];RA患者血清MMP-9水平与EMMPRIN水平呈正相关性(r=0.562,P<0.001);MMP-9预测RA患者合并颈动脉粥样硬化的ROC-AUC为0.805(95%CI:0.7024~0.9075);EMMPRIN预测RA患者合并颈动脉粥样硬化的ROC-AUC为0.729(95%CI:0.6163~0.8426)。Logistic回归分析显示年龄、病程、DAS28、hs-CRP与MMP-9是影响RA患者颈动脉粥样硬化的独立相关因素。结论RA患者血清MMP-9、EMMPRIN表达增加,RA疾病活动与患者颈动脉粥样硬化的发生密切相关,二者联合检测对动脉粥样硬化的早期诊断有一定临床意义。

The detection of micrometastases in the peripheral blood of patients with breast cancer for hSBEM mRNA and CD44V6 mRNA

Objective： Successful treatment of breast cancer greatly depends on the early detection of its metastasis, therefore a sensitive and specific biomarker for detecting dissemination of the cancer cells will help to achieve this goal. This study was to evaluate the prognostic significance of human small breast epithelial mucin （hSBEM） and CD44V6 in breast cancer. Methods： The expressions of hSBEM mRNA and CD44V6 mRNA were detected with nested reverse transcription polymerase chain reaction （nested RT-PCR） in 67 samples of breast cancer and adjacent normal breast tissue, 16 samples of breast benign lesions tissue, and 67 specimens of peripheral blood from patients with breast cancer, 16 specimens of benign breast lesions, 20 specimens of healthy volunteers, and 25 （each five cases） other carcinomas tissue samples, including those of gastric carcinoma, colorectal carcinoma, esophageal carcinoma, lung carcinoma, and ovary carcinoma, were analyzed for hSBEM mRNA expression by nested RT-PCR. Results： hSBEM mRNA expression was observed in 62/67 （92.54%） of breast cancer, 14/16 （87.50%） of breast benign lesions and 59/67 （88.05%） of normal breast tissue, with no significant differences between them （P 〉 0.05）. None of the samples from other cancer tissues were positive. In peripheral blood the expression of hSBEM mRNA was detected in 34/67 （50.75%） from patients with breast cancer, with significant increasing （P 〈 0.05） in the cases of metastatic disease （stage Ⅳ） and those with lymph node metastasis compared with localized disease （stage Ⅰ, Ⅱ and Ⅲ） and without lymph node metastasis, but its expression was not found in peripheral blood of patients with benign breast lesions or healthy volunteers. Although CD44V6 mRNA was significantly higher in breast cancer than in benign breast lesions tissue and normal breast tissue, its expression in peripheral blood show no significant difference （P 〉 0.05） in the patients with breast cancer （82.09%）, benign breast lesion （75.00%）, or healthy volunteers （70.00%）. The expressions of hSBEM mRNA and CD44V6 mRNA had no correlation with the age of the patients, size of primary tumor, histological type and estrogen or progestin receptor status （P 〉 0.05）. Conclusion： hSBEM mRNA, as assessed by nested RT-PCR, shows a mammary-specific and mammary-sensitive expression, and is a sensitive indicator of hematogeneous spread of breast cancer cell, while CD44V6 shows low sensitivity and specificity in detecting dissemination of breast cancer cell in peripheral blood, hSBEM mRNA is a promising molecular biomarker for detecting breast cancer micrometastases.

金属基聚合物复合材料短纤维桥接界面强化机理

针对金属基聚合物复合材料易诱发界面剥离损伤失效的共性问题,研究了通过多层复合组装注射成型,在聚合物复合层与粘接层界面形成短纤维桥接,实现复合界面强化。基于内聚力剥离损伤模型,构建了短纤维桥接强化界面剥离裂纹扩展断裂失效过程的模拟仿真技术,模拟建立了界面剥离裂纹快速失稳扩展断裂损伤失效临界载荷—桥接纤维特性—界面剥离断裂韧性(损伤启裂应力T_0和临界应变能释放率G_(c))的协同关联理论,诠释了短纤维桥接界面强化机理,提出了预防短纤维桥接强化界面诱发剥离裂纹快速失稳扩展失效的设计准则。结果表明,当桥接纤维密度为20根/mm^(2),可使其临界载荷增加55.9%,临界载荷受控于桥接纤维密度、初始预裂纹面积、损伤启裂应力和临界应变能释放率,且与桥接纤维密度、损伤启裂应力和临界应变能释放率呈正关联关系,而与初始预裂纹面积呈负关联关系。

Effects of Ginkgo biloba extract on expression of biomarkers during aflatoxin B_1-induced hepatocarcinogenesis in Wistar rats

Objective： The aim of this study was to study the effect of Ginkgo biloba extract （EGb761） on metabolism of afiatoxin B1 （AFB1） in Wistar rats. Methods： Seventy one Wistar rats were assigned at random to groups A, B and C. Rats in groups A, B were injected with AFB1 （intraperitoneal, 100-200 ug/kg body weight, 1-3 times/week）. Group C was normal control. Rats in group B were fed in food with EGb761, while rats in groups A, C were given normal food. Blood samples were collected and liver biopsies were performed on the 14th, 28th and 42nd week. All the rats were sacrificed on the 64th week. The incidence of hepatocarcinoma was investigated. The hepatic phase I drug-metabolizing enzyme Cytochrome-P450 （CYP450） and phase II metabolizing enzyme glutathione S-transferase （GST） were analyzed with spectrometry. Serum AFB1- lysine adduct levels were assessed with high performance liquid chromatography （HPLC）. The expression of 8-hydroxydeoxy- guanosine （8-OHdG） was measured with immunohistochemistry. Results： The incidence of hepatocellular carcinoma （HCC） in group B was significantly lower than that in group A （26.92% vs 76.00%, P 〈 0.001）. No HCC developed in group C. EGb761 showed no effects on the activities of CYP450 and GST in rat liver tissues. The level of AFB1-lysine adduct reached the peak （4356.01 pg/mg albumin） at the 14th week in group A. EGb761 significantly inhibited the formation of AFB1-lysine adduct in serum by 13.07% at the 14th week （P = 0.033）, and 73.63% at the 42nd week （P = 0.002）. The expression of 8-OHdG protein in rat liver tissues in group B was significantly lower than that in group A at the 28th, 42nd, and 64th week （P 〈 0.05）. Conclusion： The main mechanism underlying the effect of EGb761 in blocking hepatocarcinogenesis induced by AFB1 may not be fully attributable to its influence on the activity of liver phase I and phase II metabolizing enzymes. EGb761 inhibits the production of AFB1-lysine adducts, decreases the expression of 8-OHdG protein, and finally alleviates the DNA oxidative injury, which may be one of the mechanisms for the effects of EGb761 in inhibiting or delaying AFB1-induced hepatocarcinogenesis.

Expression and interaction of CDC25A and IL-6 in hepatocellular carcinoma HepG2 cells

Objective:This study was to further investigate the effect of CDC25A gene on proliferation, invasion and metastasis of hepatocellular carcinoma HepG2 cells, and to explore whether CDC25A and IL6 interact in liver cancer.Methods: HepG2 cells were transfected with lentiviral CDC25A-shRNA to specifically block the expression of CDC25A in the experimental group (KD group), transfected with lentiviral-negative shRNA as a negative control group (NC group), and the conventionally cultured HepG2 cells were blank control group (Control group). Real-time quantitative PCR and Western blot were used to detect the mRNA and protein expression levels of CDC25A and IL6.Results:The expression level of IL6 mRNA in the experimental group was 0.4650.026, which was significantly lower than that of the negative control group of 1.0940.179 and the blank control group of 1.0020.311. The difference was statistically significant(P<0.05). The protein expression level of IL6 was 0.4990.061, which was significantly lower than the negative control group of 1.3110.034 and the blank control group of 1.2530.035. The difference was statistically significant (P<0.05). Conclusions: The CDC25A gene in hepatoma HepG2 cells was silenced, while the expression of IL6 was down-regulated. CDC25A may play a role in the development and invasion of liver cancer by regulating the expression of IL6.

Cyclin-dependent kinases-based synthetic lethality: Evidence, concept, and strategy

Synthetic lethality is a proven effective antitumor strategy that has attracted great attention.Large-scale screening has revealed many synthetic lethal genetic phenotypes,and relevant smallmolecule drugs have also been implemented in clinical practice.Increasing evidence suggests that CDKs,constituting a kinase family predominantly involved in cell cycle control,are synthetic lethal factors when combined with certain oncogenes,such as MFC,TP53,and RAS,which facilitate numerous antitumor treatment options based on CDK-related synthetic lethality.In this review,we focus on the synthetic lethal phenotype and mechanism related to CDKs and summarize the preclinical and clinical discoveries of CDK inhibitors to explore the prospect of CDK inhibitors as antitumor compounds for strategic synthesis lethality in the future.

ZDHHC12-mediated claudin-3 S-palmitoylation determines ovarian cancer progression

The membrane protein claudin-3(CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both in vitro and in vivo. Of interest, CLDN3 undergoes S-palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S-palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins.Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis. Thus, our work reveals S-palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S-palmitoylation might be a potential strategy for ovarian cancer therapy.

Targeting slug-mediated non-canonical activation of c-Met to overcome chemo-resistance in metastatic ovarian cancer cells

Metastasis-associated drug resistance accounts for high mortality in ovarian cancer and remains to be a major barrier for effective treatment. In this study, SKOV3/T4, a metastatic subpopulation of ovarian cancer SKOV3 cells, was enriched to explore potential interventions against metastaticassociated drug resistance. Quantitative genomic and functional analyses were performed and found that slug was significantly increased in the SKOV3/T4 subpopulation and contributed to the high resistance of SKOV3/T4. Further studies showed that slug activated c-Met in a ligand-independent manner due to elevated levels of fibronectin and provoked integrin α V function, which was confirmed by the significant correlation of slug and p-Met levels in 121 ovarian cancer patient samples. Intriguingly,c-Met inhibitor(s) exhibited greatly enhanced anti-cancer effects in slug-positive ovarian cancer models both in vitro and in vivo. Additionally, IHC analyses revealed that slug levels were highly correlated with reduced survival of ovarian cancer patients. Taken together, this study not only uncovers the critical roles of slug in drug resistance in ovarian cancer but also highlights a promising therapeutic strategy by targeting the noncanonical activation of c-Met in slug-positive ovarian cancer patients with poor prognosis.

The dichotomous role of immunoproteasome in cancer:Friend or foe?

Immunoproteasome is a variant of proteasome with structural differences in 20S subunits optimizing them for the production of antigenic peptides with higher binding affinity to major histocompatibility complex(MHC)-I molecules.Apart from this primary function in antigen presentation,immunoproteasome is also responsible for the degradation of proteins,both unfolded proteins for the maintenance of protein homeostasis and tumor suppressor proteins contributing to tumor progression.The altered expression of immunoproteasome is frequently observed in cancers;however,its expression levels and effects vary among different cancer types exhibiting antagonistic roles in tumor development.This review focuses on the dichotomous role of immunoproteasome in different cancer types,as well as summarizes the current progression in immunoproteasome activators and inhibitors.Specifically targeting immunoproteasome may be a beneficial therapeutic intervention in cancer treatment and understanding the role of immunoproteasome in cancers will provide a significant therapeutic insight for the prevention and treatment of cancers.

Phosphorylation regulates cullin-based ubiquitination in tumorigenesis

Cullin-RING ligases(CRLs)recognize and interact with substrates for ubiquitination and degradation,and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes.Phosphorylation,either of substrates or receptors of CRLs,can alter their interaction.Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases,most often tumorigenesis.These processes have the potential to be used for tumor intervention through the regulation of the activities of related kinases,along with the regulation of the stability of specific oncoproteins and tumor suppressors.This review describes the mechanisms and biological functions of crosstalk between phosphorylation and ubiquitination,and most importantly its influence on tumorigenesis,to provide new directions and strategies for tumor therapy.

Blockade of deubiquitinase YOD1 degrades oncogenic PML/RARα and eradicates acute promyelocytic leukemia cells

In most acute promyelocytic leukemia(APL)cells,promyelocytic leukemia(PML)fuses to retinoic acid receptor α (RARα)due to chromosomal translocation,thus generating PML/RARαoncoprotein,which is a relatively stable oncoprotein for degradation in APL.Elucidating the mechanism regulating the stability of PML/RARαmay help to degrade PML/RARαand eradicate APL cells.Here,we describe a deubiquitinase(DUB)-involved regulatory mechanism for the maintenance of PML/RARαstability and develop a novel pharmacological approach to degrading PML/RARαby inhibiting DUB.We utilized a DUB siRNA library to identify the ovarian tumor protease(OTU)family member deubiquitinase YOD1 as a critical DUB of PML/RARα.Suppression of YOD1 promoted the degradation of PML/RARα,thus inhibiting APL cells and prolonging the survival time of APL cell-bearing mice.Subsequent phenotypic screening of small molecules allowed us to identify ubiquitin isopeptidase inhibitor I(G5)as the first YOD1 pharmacological inhibitor.As expected,G5 notably degraded PML/RARαprotein and eradicated APL,particularly drug-resistant APL cells.Importantly,G5 also showed a strong killing effect on primary patient-derived APL blasts.Overall,our study not only reveals the DUB-involved regulatory mechanism on PML/RARαstability and validates YOD1 as a potential therapeutic target for APL,but also identifies G5 as a YOD1 inhibitor and a promising candidate for APL,particularly drug-resistant APL treatment.

Simulation and detection of the topological properties of a modulated Rice-Mele model in a one-dimensional circuit-QED lattice

Here, we propose a simple scheme to realize a one-dimensional （1D） modulated Rice-Mele model （RMM） and investigate its topological properties with a 1D circuit quantum electrodynamics （QED） lattice. The system can be mapped into a Chern insulator model by introducing a period parameter. Interestingly and surprisingly, we found that the circuit-QED lattice system always exhibits topologically nonttrvial phases if both the nearest-neighbor hopping strength between two resonators and the qubitassisted on-site potentials are alternately changed in the direction of the lattice. The numerical results show that the topological phases can be obtained by introducing an additional modulation parameter and both the edge state and topological invariant can be unambiguously seen with the existence of decay and disorders, even with few resonators in the lattice.

Deubiquitination complex platform:A plausible mechanism for regulating the substrate specificity of deubiquitinating enzymes

Deubiquitinating enzymes(DUBs) or deubiquitinases facilitate the escape of multiple proteins from ubiquitin-proteasome degradation and are critical for regulating protein expression levels in vivo.Therefore,dissecting the underlying mechanism of DUB recognition is needed to advance the development of drugs related to DUB signaling pathways.To data,extensive studies on the ubiquitin chain specificity of DUBs have been reported,but substrate protein recognition is still not clearly understood.As a breakthrough,the scaffolding role may be significant to substrate protein selectivity.From this perspective,we systematically characterized the scaffolding proteins and complexes contributing to DUB substrate selectivity.Furthermore,we proposed a deubiquitination complex platform(DCP) as a potentially generic mechanism for DUB substrate recognition based on known examples,which might fill the gaps in the understanding of DUB substrate specificity.

Disulfiram enhances the antitumor activity of cisplatin by inhibiting the Fanconi anemia repair pathway

A series of chemotherapeutic drugs that induce DNA damage,such as cisplatin(DDP),are standard clinical treatments for ovarian cancer,testicular cancer,and other diseases that lack effective targeted drug therapy.Drug resistance is one of the main factors limiting their application.Sensitizers can overcome the drug resistance of tumor cells,thereby enhancing the antitumor activity of chemotherapeutic drugs.In this study,we aimed to identify marketable drugs that could be potential chemotherapy sensitizers and explore the underlying mechanisms.We found that the alcohol withdrawal drug disulfiram(DSF)could significantly enhance the antitumor activity of DDP.JC-1 staining,propidium iodide(PI)staining,and western blotting confirmed that the combination of DSF and DDP could enhance the apoptosis of tumor cells.Subsequent RNA sequencing combined with Gene Set Enrichment Analysis(GSEA)pathway enrichment analysis and cell biology studies such as immunofluorescence suggested an underlying mechanism:DSF makes cells more vulnerable to DNA damage by inhibiting the Fanconi anemia(FA)repair pathway,exerting a sensitizing effect to DNA damaging agents including platinum chemotherapy drugs.Thus,our study illustrated the potential mechanism of action of DSF in enhancing the antitumor effect of DDP.This might provide an effective and safe solution for combating DDP resistance in clinical treatment.

WSB1 regulates c-Myc expression through β-catenin signaling and forms a feedforward circuit

The dysregulation of transcription factors is widely associated with tumorigenesis.As the most well-defined transcription factor in multiple types of cancer,c-Myc can transform cells by transactivating various downstream genes.Given that there is no effective way to directly inhibit c-Myc,c-Myc targeting strategies hold great potential for cancer therapy.In this study,we found that WSB1,which has a highly positive correlation with c-Myc in 10 cancer cell lines and clinical samples,is a direct target gene of c-Myc,and can positively regulate c-Myc expression,which forms a feedforward circuit promoting cancer development.RNA sequencing results from Bel-7402 cells confirmed that WSB1 promoted cMyc expression through theβ-catenin pathway.Mechanistically,WSB1 affectedβ-catenin destruction complex-PPP2CA assembly and E3 ubiquitin ligase adaptorβ-TRCP recruitment,which inhibited the ubiquitination ofβ-catenin and transactivated c-Myc.Of interest,the effect of WSB1 on c-Myc was independent of its E3 ligase activity.Moreover,overexpressing WSB1 in the Bel-7402 xenograft model could further strengthen the tumor-driven effect of c-Myc overexpression.Thus,our findings revealed a novel mechanism involved in tumorigenesis in which the WSB1/c-Myc feedforward circuit played an essential role,highlighting a potential c-Myc intervention strategy in cancer treatment.

AKT inhibitor Hu7691 induces differentiation of neuroblastoma cells

While neuroblastoma accounts for 15%of childhood tumor-related deaths,treatments against neuroblastoma remain scarce and mainly consist of cytotoxic chemotherapeutic drugs.Currently,maintenance therapy of differentiation induction is the standard of care for neuroblastoma patients in clinical,especially high-risk patients.However,differentiation therapy is not used as a first-line treatment for neuroblastoma due to low efficacy,unclear mechanism,and few drug options.Through compound library screening,we accidently found the potential differentiation-inducing effect of AKT inhibitor Hu7691.The protein kinase B(AKT)pathway is an important signaling pathway for regulating tumorigenesis and neural differentiation,yet the relation between the AKT pathway and neuroblastoma differentiation remains unclear.Here,we reveal the anti-proliferation and neurogenesis effect of Hu7691 on multiple neuroblastoma cell lines.Further evidence including neurites outgrowth,cell cycle arrest,and differentiation mRNA marker clarified the differentiation-inducing effect of Hu7691.Meanwhile,with the introduction of other AKT inhibitors,it is now clear that multiple AKT inhibitors can induce neuroblastoma differentiation.Furthermore,silencing AKT was found to have the effect of inducing neuroblastoma differentiation.Finally,confirmation of the therapeutic effects of Hu7691 is dependent on inducing differentiation in vivo,suggesting that Hu7691 is a potential molecule against neuroblastoma.Through this study,we not only define the key role of AKT in the progression of neuroblastoma differentiation but also provide potential drugs and key targets for the application of differentiation therapies for neuroblastoma clinically.

Front

Certain post-translational modifications are required for proteins quality control and intracellular transportation. Here, Yuan et al. found that S-palmitoylation played an important role in the intracellular transport of CLDN3, a tight junction protein involved in ovarian cancer progression. Mechanistically, ZDHHC12-mediated S-palmitoylation is prerequisite for CLDN3 transporting to the cell membrane.