Distinctive tumorigenic significance and innovative oncology targets of SUMOylation.

Protein SUMOylation, a post-translational modification, intricately regulates diverse biological processes including gene expression, cell cycle progression, signaling pathway transduction, DNA damage response, and RNA metabolism. This modification contributes to the acquisition of tumorigenicity and the maintenance of cancer hallmarks. In malignancies, protein SUMOylation is triggered by various cellular stresses, promoting tumor initiation and progression. This augmentation is orchestrated through its specific regulatory mechanisms and characteristic biological functions. This review focuses on elucidating the fundamental regulatory mechanisms and pathological functions of the SUMO pathway in tumor pathogenesis and malignant evolution, with particular emphasis on the tumorigenic potential of SUMOylation. Furthermore, we underscore the potential therapeutic benefits of targeting the SUMO pathway, paving the way for innovative anti-tumor strategies by perturbing this dynamic and reversible modifying process.

Erratum: A Novel Pak1/ATF2/miR-132 Signaling Axis Is Involved in the Hematogenous Metastasis of Gastric Cancer Cells.

[This corrects the article DOI: 10.1016/j.omtn.2017.07.005.].

Potential roles of PIWI-interacting RNAs in breast cancer, a new therapeutic strategy.

Breast cancer (BC) has been the focus of numerous studies aimed at identifying novel biological markers for its early detection. PIWI-interacting RNAs (piRNAs), a subset of small non-coding RNAs, have emerged as potential markers due to their aberrant expression in various cancers. PiRNAs have recently gained attention due to their aberrant expression in various cancers, including BC. PiRNAs, exhibit diverse biological activities, such as epigenetic regulation of gene and protein expression and their association with cell proliferation and metastasis has been well-established. As the field of non-coding RNAs rapidly evolves, there is great anticipation that therapies targeting piRNAs will advance swiftly. This review will delve into the various biological functions of piRNAs, such as gene suppression, transposon silencing, and epigenetic regulation of genes. The review will also highlight the role of piRNAs as either progenitors or suppressors in cancers, with a particular focus on BC. Lastly, it will touch upon the potential of piRNAs as biomarkers and therapeutic targets for BC.

Acute Effects of Local High-Frequency Percussive Massage on Deep Fascial and Muscular Stiffness and Joint Range of Motion in Young Adult Men.

BACKGROUND: Local high-frequency percussive (HFP) massage has recently found widespread application in physical therapy. Although HFP massage reportedly improves range of motion (ROM), the mechanism underlying its action has not yet been proven. This study aimed to clarify whether a 5-minute percussive massage regimen affects muscular or connective tissues, such as the deep fascia and deep intermuscular fascia and the change in joint ROM. METHOD: The study sample was calculated using G*Power analysis program, and this study enrolled 15 healthy men who underwent 5-minute HFP massage to the medial gastrocnemius muscle. Shear-wave elastography was used to measure tissue stiffness in the deep fascia, muscle, and deep intermuscular fascia through shear-wave velocity as well as the ROM of the volunteers' ankle joint dorsiflexion before and after the HFP massage. A value of P < .05 was used to declare statistical significance, and post hoc was used to calculate the effect size using G*Power. RESULTS: Shear-wave velocity revealed a significant change in the deep fascia (P = .003; shear-wave velocity: -0.7 m/s) and significant increase in ROM of ankle dorsiflexion (P = .002; increase in ROM: 3.0°) after 5 minutes of HFP massage. However, the muscle and deep intermuscular fascia did not exhibit any significant changes. CONCLUSIONS: HFP massage for 5 minutes modified the stiffness of the deep fascia and concurrently improved the ankle joint-dorsiflexion ROM. This method can be used as an intervention to decrease stiffness of the deep fascia and increase the ROM efficiently.

Lead exposure induces neuronal apoptosis via NFκB p65/RBBP4/Survivin signaling pathway.

Lead (Pb), as a heavy metal that is easily exposed in daily life, can cause damage to various systems of body. Apoptosis is an autonomous cell death process regulated by genes in order to maintain the stability of internal environment, which plays an important role in the development of nervous system. RB binding protein 4 (RBBP4) is one of the core histone binding subunits and is closely related to the apoptosis process of nervous system cells. However, it is not known whether RBBP4 can regulate neuronal apoptosis in lead-exposed environments. We exposed PC12 cells to 0 µM (control group), 1 µM, and 100 µM PbAc for 24 h to obtain cell samples. The female rats ingested drinking water containing 0, 0.5 g/L, and 2.0 g/L PbAc from the first day of pregnancy to three weeks after delivery to obtain hippocampal tissue samples from mammary rats. The results of TUNEL showed that lead exposure promoted the onset of apoptosis in cells and hippocampus. The mRNA and protein levels of the apoptosis-related protein Survivin were significantly reduced in the lead-exposed group compared to the control group. In addition, we found that lead exposure reduces the mRNA and protein levels of RBBP4 in PC12 cells and hippocampus, and increases the mRNA and protein levels of NFκB p65. Moreover, inhibiting NFκB p65 can reverse the decrease in RBBP4 expression in the lead exposure model. Overexpression of RBBP4 increased Survivin expression and reduced apoptosis induced by lead exposure. This suggests that lead exposure induces apoptosis through the NFκB p65/RBBP4/Survivin signaling pathway.

Evaluation of the safety and efficacy of transarterial sevelamer embolization in a rabbit liver cancer model: A challenge on the size rule for vascular occlusion.

As the most efficient method to treat hepatocellular carcinoma in the immediate or advanced stage, transarterial chemoembolization (TACE) is coming into the era of microsphere (MP). Drug-eluting beads have shown their huge potential as an embolic agent and drug carrier for chemoembolization, but their sizes are strictly limited to be above 40 µm, which was considered to occlude vessels in a safe mode. microsphere smaller than 40 µm is easy to be washed out and transported to the normal liver lobe or other organs, causing severe adverse events and failed embolization. To determine whether sevelamer ultrafine particle (0.2-0.5 µm) is qualified as a safe and efficient embolic agent, we investigated the safety and therapeutic efficiency of transarterial sevelamer embolization (TASE) in the VX2 rabbit liver cancer model, aiming to challenge the "40 µm" rule on the selection criteria of the MP. In a four-arm study, blank bead (Callisphere, 100-300 µm), luminescent polystyrene microsphere (10, 100 µm), and sevelamer particle were transarterially administered to evaluate the threshold size of the MP size for intrahepatic or extrahepatic permeability. Another four-arm study was designed to clarify the safety and efficiency of preclinical transarterial sevelamer embolizationTASE tests over other techniques. Sham (saline), TASE, C-TACE, and D-TACE (n = 6) were compared in terms of serum chemistry, histopathology, and tumor necrosis ratio. In the first trials, the "40 µm" rule was detectable on the VX2 cancer model, but the regulation has no application to the new embolic agent as sevelamer ultrafine particles have not been found to leak out from the VX2 lesions, only found in the embolized vessels. Pathology proves that less viable tumor residue was found 2 weeks after the procedure, evidencing a better therapeutic outcome. No adverse events were found except for a short stress response. These results indicate that sevelamer is a safe and efficient embolic as an alternative to the current MP-based embolization therapy techniques.

Pi-inducedin-situaggregation of sevelamer nanoparticles for vascular embolization.

Decades have witnessed rapid progress of polymeric materials for vascular embolic or chemoembolic applications. Commercially available polymeric embolics range from gelatin foam to synthetic polymers such as poly(vinyl alcohol). Current systems under investigation include tunable, bioresorbable microspheres composed of chitosan or poly(ethylene glycol) derivatives,in situgelling liquid embolics with improved safety profiles, and radiopaque embolics that are trackablein vivo. In this paper, we proposed a concept of 'responsive embolization'. Sevelamer, clinically proved as an inorganic phosphate binder, was ground into nanoparticles. Sevelamer nanoparticle is highly mobile and capable of swelling and aggregating in the presence of endogenous inorganic phosphate, thereby effectively occluding blood flow in the vessel as it was administered as an embolic agent for interventional therapy. Moreover, citrated sevelamer nanoparticles delayed the aggregation, preferable to penetrate deeply into the capillary system. On the rabbit VX2 liver cancer model, both sevelamer particles aggregates occlude the tumor feeding artery, but backflow was found for the pristine one, thereby citrate passivation of sevelamer nanoparticles endows it have potential from 'bench to bedside' as a new type of vascular embolic.

PAK5 promotes RNA helicase DDX5 sumoylation and miRNA-10b processing in a kinase-dependent manner in breast cancer.

P21-activated kinase 5 (PAK5) plays an important role in tumors. However, the functional role of PAK5 in mammary tumorigenesis in vivo remains unclear. Here, we show that PAK5 deficiency represses MMTV-PyVT-driven breast tumorigenesis. DEAD-box RNA helicase 5 (DDX5) is a substrate of PAK5, which is phosphorylated on threonine 69. PAK5-mediated DDX5 phosphorylation promotes breast cancer cell proliferation and metastasis. The increased expression levels of PAK5 and phospho-DDX5 threonine 69 are associated with metastasis and poor clinical outcomes of patients. PAK5 facilitates the phosphorylation-dependent sumoylation of DDX5 to stabilize DDX5. Both the phosphorylation and sumoylation of DDX5 enhance the formation of a DDX5/Drosha/DGCR8 complex, thus promoting microRNA-10b processing. Finally, we verify decreased expression of DDX5 phosphorylation and sumoylation and mature miR-10b in PAK5-/-/MMTV-PyVT transgenic mice. Our findings provide insights into the function of PAK5 in microRNA (miRNA) biogenesis, which might be a potential therapeutic target for breast cancer.

Effect of atrazine on accumulation of iron via the iron transport proteins in the midbrain of SD rats.

Atrazine (ATR), a widely used herbicide that belongs to the triazine class, has detrimental effects on several organ systems. It has also been shown that ATR exposure results in dopaminergic neurotoxicity. However, the mechanism of herbicides causing ferroptosis in neurons is less concerned. So, the present study aimed to investigate the effects of long-term oral exposure to ATR on ferroptosis in adult male rats. In this study, we show that there was a dose-dependent increase in the concentration of iron in the midbrain. Simultaneously, the expression of tyrosine hydroxylase (TH) and Synuclein (α-syn) were altered by the ATR. We carried out miRNA profiling brain tissue in order to identify factors that mediate ferroptosis. We also found that the mRNA and protein expression of the transferrin receptor (TFR), divalent metal transporter 1 (DMT1), hephaestin (HEPH), and ferroportin 1 (Fpn1) in the midbrain were affected by ATR. Based on the current results and previously published data, it is clear that exposure of adult male rats to high doses of ATR leads to iron loading in the midbrain. The long-term adverse effects of ATR on the midbrain have a special relevance after exposure.

PAK5-mediated AIF phosphorylation inhibits its nuclear translocation and promotes breast cancer tumorigenesis.

Although p21 activated kinase 5 (PAK5) is related to the progression of multiple cancers, its biological function in breast cancer remains unclear. Apoptosis-inducing factor (AIF) is a vital apoptosis factor in mitochondria, which can be released from mitochondria and enter the nucleus, causing caspase-independent apoptosis. In this study, we reveal that PAK5 inhibits apoptosis by preventing the nuclear translocation of AIF. PAK5 inhibits the release of AIF from mitochondria in breast cancer cells by decreasing the mitochondria membrane permeability and increasing the membrane potential. Furthermore, PAK5 phosphorylates AIF at Thr281 site to inhibit the formation of AIF/importin α3 complex, leading to decrease AIF nuclear translocation. Functionally, we demonstrate that PAK5-mediated AIF phosphorylation promotes the proliferation of breast cancer cells and accelerates the growth of breast cancer in vivo. Significantly, PAK5 and AIF expression in breast cancer are positively correlated with poor patient prognosis. PAK5 expression is negatively correlated with AIF nuclear translocation. These results suggest that PAK5-AIF signaling pathway may play an essential role in mammary tumorigenesis, providing a new therapeutic target for the treatment of breast cancer.

Nanosized drug-eluting bead for transcatheter arterial chemoembolization (ND-TACE).

Commercially available drug-eluting embolization beads (100-500 µm) reduced the occurrence of adverse events related to an anticancer drug, but were unascertained to remarkably benefit the transcatheter arterial chemoembolization (TACE) treatment of intermediate-stage liver cancer. Dextran-coated arsenite nanoparticles with the size ranging from 400 to 600 nm were developed as a nanosized drug-eluting bead (NDEB) for chemoembolization therapy of the rabbit VX2 liver tumor. We fully characterized their relevant physicochemistry and drug release properties. Their hemolysis was investigated before vessel embolization. The introduction of the NDEB allowed continuous embolization of tumor feeding vessels and sustained release of arsenic trioxide, thereby causing severe tumor necrosis and reduced vascularity. Sonography including B mode ultrasound, color Doppler flow imaging (CDFI) and dynamic contrast-enhanced ultrasound (CEUS) were performed to evaluate the tumor vascularity and viability. Additionally, its hepatotoxicity was tolerable at a medium dose. NDEB-TACE might be an effective therapeutic strategy for interventional therapy.

PAK4 phosphorylating RUNX1 promotes ERα-positive breast cancer-induced osteolytic bone destruction.

The biological function of nuclear PAK4 in ERα-positive breast cancer osteolytic bone destruction remains unclear. Here, we find that the nuclear PAK4 promotes osteoclastogenesis and tumor-induced osteolysis via phosphorylating RUNX1. We show that nuclear PAK4 interacts with and phosphorylates RUNX1 at Thr-207, which induces its localization from the nucleus to the cytoplasm and influences direct interaction with SIN3A/HDAC1 and PRMT1. Furthermore, we reveal that RUNX1 phosphorylation by PAK4 at Thr-207 promotes osteolytic bone destruction via targeting downstream genes related to osteoclast differentiation and maturation. Importantly, we verify changes in RUNX1 subcellular localization when nuclear PAK4 is positive in breast cancer bone metastasis tissues. Functionally, we demonstrate that RUNX1 phosphorylation promotes osteolytic bone maturation and ERα-positive breast cancer-induced osteolytic bone damage in the mouse model of orthotopic breast cancer bone metastasis. Our results suggest PAK4 can be a therapeutic target for ERα-positive breast cancer osteolytic bone destruction.

Gene expression and prognosis of sirtuin family members in ovarian cancer.

Sirtuins (SIRTs), a class of nicotinamide-adenine dinucleotide (NAD)+-dependent deacetylases, involve in modulating carcinogenesis and progression of various malignancies through their regulation of the cancer metabolism. However, the expression profiles and prognostic roles of SIRTs in ovarian cancer (OC) remain unclear. We underscore the transcriptional expression and prognostic significance of SIRTs in OC patients using online databases. Gene Expression Profiling Interactive analysis (GEPIA) was applied to analyze mRNA expression, and Kaplan-Meier plotter was used to evaluate prognostic value. In patients with OC, SIRT1/2/3 were significantly down-regulated, while rest of SIRTs were not significantly changed. High SIRT2/5/6/7 expression was correlated with favorable overall survival (OS), while high SIRT1/4 expression was correlated with poor OS. Additionally, aberrant SIRTs mRNA levels were related to the prognosis of OC patients with different clinicopathological characteristics. This is the first study to integrate bioinformatics approaches intended to identify the expression profiles and prognostic value of SIRTs in OC. These results suggest that SIRTs is related to the prognosis of OC and may be the potential therapeutic interventions in OC.

Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways.

OBJECTIVE: Human oral squamous cell carcinoma (OSCC) is a major cause of mortality and morbidity worldwide. There is an urgent need to identify bioactive molecules and potential target genes that could inhibit carcinogenesis for OSCC therapy. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring flavonoid, has been previously shown to have anti-proliferative activities in OSCC; however, its molecular mechanism is unknown. METHODS: Colony formation, cell viability, Boyden chamber, wound healing, and tumor xenograft assays were used to detect the impact of fisetin on OSCC cells in vitro and in vivo. Western blot analysis was used to examine the corresponding protein expression. RESULTS: Fisetin treatment significantly inhibited proliferation and promoted apoptosis by repressing PAK4 expression. Moreover, fisetin treatment attenuated cell migration by blocking PAK4 signaling pathways. In addition, the tumor xenograft showed anti-tumor growth effects of fisetin exposure in vivo. CONCLUSION: Fisetin may represent a potential therapeutic strategy for human OSCC by targeting PAK4 signaling pathways.

MAGE-A11 Expression Predicts Patient Prognosis in Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) are the sixth most common cancer worldwide. Growing evidence showed that Melanoma-associated antigen-A11 (MAGE-A11) was abnormally expressed in various malignancies, but MAGE-A11 expression and its biological roles in HNSCC had not been reported in detail. The aim of the study was to investigate the association between MAGE-A11 signatures and clinicopathological features of HNSCC patients and uncover its potential mechanisms in HNSCC patients. METHODS: In the present study, we analyzed the expression of MAGE-A11 gene and evaluated the impact of MAGE-A11 genes expression on clinical outcome from the Cancer Genome Atlas (TCGA) database. MAGE-A11 expression was assessed in a well-characterized series of HNSCC (N = 75) with long-term follow-up and 10 cases of adjacent non-cancerous tissues, which were diagnosed between 2013 and 2014, by using immunohistochemistry. The correlation between MAGE-A11 expression and clinicopathological factors was analyzed. Kaplan-Meier and Cox regression analyses were used to assess the prognostic significance of MAGE-A11 expression among HNSCC patients. RESULTS: The results showed that MAGE-A11 mRNA expression was increased in HNSCC tissues compared to "normal" tissues (P < 10-12). MAGE-A11 protein expression was not correlated with lymph node status, relapse, age, gender, histological grade, differentiation, clinical stage, tumor size, radiotherapy or chemotherapy. The patients with high MAGE-A11 expression had lower 5-year overall survival (OS) rates than those with low MAGE-A11 expression as determined using the Kaplan-Meier method. The univariate and multivariate analyses confirmed that elevated MAGE-A11 was an independent prognostic factor for the OS of HNSCC patients. CONCLUSION: These findings indicate that MAGE-A11 may be a valuable diagnostic or prognostic marker as well as a potential molecular therapy target for HNSCC patients.

Will Arsenic Trioxide Benefit Treatment of Solid Tumor by Nano- Encapsulation?

Arsenic trioxide (ATO) has remarkably enhanced therapeutic efficacy in treating both newly diagnosed and relapsed patients suffering from Acute Promyelocytic Leukemia (APL). Unfortunately, whether as a single agent, component of combined chemotherapy, or as a chemosensitizer or radiosensitizer combined with interventional therapy/radiotherapy, it did not benefit treatment of solid tumor (liver cancer, bladder cancer, glioma, breast cancer, cervical cancer, colorectal cancer, lung cancer, and melanoma) as seen from the clinical trials reported from the published journals or FDA-approved trials in the past decades. The clinical outcome failed to live up to our expectations, which was attributed to severe systemic toxicity and inappropriate pharmacokinetic such as low delivery efficiency and rapid renal elimination. Nanomedicine is designed to fuel up pharmaceuticals and polish off adverse effects by the moderation of their absorption, distribution, metabolism, and excretion. Nevertheless, quite a few nanodrugs (such as Doxil, Abraxane) were approved to be used clinically, and "from bench to bedside" it seems to be no easy way for most of them, such as nano-ATO. Encapsulating ATO into several types of nano-vehicles (liposome, polymer micelle, porous silicon, etc.), nano-TO can improve pharmacokinetic and become a prominent candidate to penetrate into tumor tissue, but so far no nano- ATO clinical trials have been approved around the world. On summarizing the clinical trials of ATO on solid tumor and preclinical study of nano-ATO, it is believed there is still a chance for ATO to play a critical co-helper in a comprehensive therapy to fight with solid tumor.

A PAK5-DNPEP-USP4 axis dictates breast cancer growth and metastasis.

Although clinically associated with the progression of multiple cancers, the biological function of p21-activated kinase 5 (PAK5) in breast cancer remains largely unknown. Here, we reveal that the PAK5-aspartyl aminopeptidase (DNPEP)-ubiquitin-specific protease 4 (USP4) axis is involved in breast cancer progression. We show that PAK5 interacts with and phosphorylates DNPEP at serine 119. Functionally, we demonstrate that DNPEP overexpression suppresses breast cancer cell proliferation and invasion and restricts breast cancer growth and metastasis in mice. Furthermore, we identify USP4 as a downstream target of the PAK5-DNPEP pathway; DNPEP mediates USP4 downregulation. Importantly, we verify that DNPEP expression is frequently downregulated in breast cancer tissues and is negatively correlated with PAK5 and USP4 expression. PAK5 decreases DNPEP abundance via the ubiquitin-proteasome pathway. Consistently, analyses of clinical breast cancer specimens revealed significantly increased PAK5 and USP4 levels and an association between higher PAK5 and USP4 expression and worse breast cancer patient survival. These findings suggest a pivotal role for PAK5-elicited signaling in breast cancer progression.

Effect of the imatinib treatment regimen on the postoperative prognosis of patients with high-risk gastrointestinal stromal tumors.

Background: Surgical resection is the standard treatment for localized and potentially resectable gastrointestinal stromal tumors (GISTs), If the postoperative pathology diagnosis indicates that patients are at high risk of recurrence, they should be treated with imatinib. Even though the introduction of imatinib substantially improved the outcome of GIST patients, it is unclear whether different imatinib treatment regimens affect patients' survival. Methods: This retrospective study included 120 patients who underwent tumor resection for high-risk GISTs between January 2009 and October 2018. The patients were divided into three groups: one group of patients received postoperative imatinib adjuvant therapy regularly (regular treatment group); the second group was not treated with imatinib until they were found to have disease progression (observation group); the third group was treated with postoperative imatinib adjuvant therapy irregularly (irregularly treatment group). The progression-free survival (PFS) and overall survival (OS) were compared between the three groups, and the prognostic risk factors were analysed by the Cox regression model. Results: The median PFS was 45 months (range: 25-59). The 3- and 5-year PFS values were 71.3% and 49.9%, respectively. The PFS in the regular group was longer than in the observation group and irregular group (P<0.001). The median OS was 59 months (range:47-78). The 3- and 5-year OS values were 91.6% and 84.2%, respectively. There were no differences in OS among the three groups (P=0.150). The extent of radical resection (P<0.001) and intraoperative tumor rupture (P=0.005) were independent prognostic factors influencing OS. Conclusions: Irregular administration of imatinib was associated with a worse PFS, but it did not affect the OS of patients with high-risk GISTs. Avoiding intraoperative tumor rupture and R0 resection were associated with better survival.

A novel PAK4-CEBPB-CLDN4 axis involving in breast cancer cell migration and invasion.

Claudin-4 (CLDN4), a crucial member of tight junction proteins, is aberrantly expressed in breast cancer cells and contributes to cell migration and invasion. However, the mechanisms controlling CLDN4 expression in breast cancer are poorly understood. Here, we reported that CLDN4 expression correlated positively with p21-activated kinase 4 (PAK4) expression in human breast cancer tissues. Knockdown of PAK4 in MDA-MB-231 and ZR-75-30 cells suppressed CLDN4 expression and significantly inhibited cell migration and invasion. Conversely, restoration of CLDN4 expression in PAK4-knockdown cells reversed the inhibition of migration and invasion. We identified CCAAT/enhancer-binding protein ß (CEBPB) as a novel transcriptional regulator of CLDN4 and confirmed that CEBPB bound to the -1093 to -991 bp region of the CLDN4 promoter. Importantly, we found that PAK4 enhanced CEBPB phosphorylation on Thr-235. In summary, we showed that PAK4-mediated CEBPB activation upregulated CLDN4 expression to promote breast cancer cell migration and invasion. Our results might contribute to understanding the mechanisms of CLDN4 regulation and suggest PAK4-CEBPB-CLDN4 axis as a potential therapeutic target for breast cancer.

Pb exposure reduces the expression of SNX6 and Homer1 in offspring rats and PC12 cells.

Lead (Pb) is a widespread environmental heavy metal toxicant and chronic Pb exposure can have irreversible effects on memory and cognitive function, which is closely related to dendritic spines. Studies have shown that SNX6 and Homer1 can regulate the growth of dendritic spines. We aimed to investigate the effect of Pb exposure on the dendritic spines in hippocampus, the expression of SNX6 and Homer1 in rats and PC12 cells. The animals were randomly divided to three groups: control group, low lead group and high lead group. PC12 cells were divided into 3 groups: 0 µM, 1 µM and 100 µM Pb acetate. The results showed that the Pb levels in blood and hippocampus of all exposure groups were significantly higher than that of the control group. The morphology of dendritic spines in hippocampus after Pb treatment was changed and the density of dendritic spines was reduced. The expression of SNX6 and Homer1 was decreased in Pb exposed groups compared with the control group. Furthermore, up-regulation of SNX6 expression could reverse the down-regulation of Pb exposure on Homer1. These results indicate that Pb exposure can reduce the expression of SNX6 and lead to a decrease in Homer1 expression, which affects the changes in dendritic spines causing learning and memory impairment.