Unraveling early recurrence of risk factors in Gallbladder cancer: A systematic review and meta-analysis.

BACKGROUND: Gallbladder cancer (GBC) is the most prevalent biliary tract tumor characterized by a high incidence of recurrence, even after curative-intent surgery. The object of this systematic review and meta-analysis was to investigate the risk factors related to early recurrence (ER). METHODS: A systematic literature review was conducted in PubMed, Embase, Cochrane Library, and Web of Science to identify published articles up to February 2024. Data on risk factors associated with ER reported by two or more studies were collected. Selection of different effect models based on data heterogeneity. RESULTS: Out of 6497 initially identified articles based on our search strategies, only 5 were eligible and included in this meta-analysis and 12 ER-related factors were collected. The overall recurrence rate was reported between 32.3% and 61.0 %, and the ER rate ranged from 19.6% to 26.5 %. Concentrations of CA19-9 (OR 3.03 95 % CI 2.20-4.17) and CEA (OR 1.85 95 % CI 1.24-2.77), tumor differentiation (OR 2.79, 95 % CI 1.86-4.20), AJCC T stage (OR 7.64, 95%CI 3.40-17.18), lymphovascular invasion (OR 2.71, 95 % CI 1.83-4.03), perineural invasion (OR 2.71, 95 % CI 1.79-4.12), liver involvement (OR 5.69, 95%CI 3.78-8.56) and adjuvant therapy (OR 2.19, 95 % CI 1.06-4.55) were identified as the risk factors of ER. CONCLUSION: This study may provide valuable insights for early identification of increased ER risk and making informed decisions regarding the comprehensive diagnosis and treatment of patients with GBC. To draw more definitive conclusions, there is a need for high-quality prospective studies involving multiple centers and diverse racial populations.

The potential up-regulation risk of 3' UTR SNP (rs10787760 G > A) for the VAX1 gene is associated with NSCLP in the northwest Chinese population.

AIMS: To investigate the association between single nucleotide polymorphisms (SNPs) in 3'UTR region of VAX1, SYT14 and PAX7 genes and the risk of non-syndromic cleft palate (NSCLP) in a northwest Chinese population. MAIN METHODS: A case-control study was conducted in 406 normal controls and 399 NSCLP patients. Using iMLDRTM genotyping technology, eight SNPs of three genes ((rs10787760, rs7086344 at VAX1), (rs1010113, rs851114, and rs485874 at PAX7), and (rs61820397, rs4609425, rs12133399 at SYT14)) were genotyped to investigate the differences in alleles and genotype distribution frequencies between NSCLP patients and healthy controls. RNA Folding Form software was used to predict RNA secondary structure and expression vectors were constructed to explore the function of the relevant SNP. The effect of SNP polymorphism of gene transcription and translation was assessed using qPCR and Western blot analysis. KEY FINDINGS: Among the eight SNPs of three genes, rs10787760 of VAX1 gene was found to be associated with an increased risk of NSCLP (OR = 1.341, CI = 1.004-1.790) and the GA genotype of rs10787760 increased the risk of cleft lip and/or palate (CL/P) about 1.42 times (p < 0.05), and carrying the A allele might increase the risk of NSCL/P in male (OR = 1.356, 95 % CI = 1.010-1.823). But there was no association observed with cleft palate only (CPO). Cell function experiments revealed that the G to A mutation in rs10787760 up-regulated GFP-VAX1 transcriptional level by 2.39 and 3.13 times in two cell lines respectively, and enhance the protein expression of the VAX1 gene further. RNA secondary structure study showed that the rs10787760 (G > A) had two different secondary structures in 3'UTR region. SIGNIFICANCE: The rs10787760 variant in the 3'UTR region of VAX1 gene is associated with CL/P in northwest Chinese population. We hypothesize that the machanism of it might be caused by the RNA differenct fold in the 3'UTR region caused by the polymorphism of the gene. LEVEL OF EVIDENCE: Original Reports.

Unraveling Intracellular Protein Corona Components of Nanoplastics via Photocatalytic Protein Proximity Labeling.

Bioaccumulation of nanoplastic particles has drawn increasing attention regarding environmental sustainability and biosafety. How nanoplastic particles interact with the cellular milieu still remains elusive. Herein, we exemplify a general approach to profile the composition of a "protein corona" interacting with nanoparticles via the photocatalytic protein proximity labeling method. To enable photocatalytic proximity labeling of the proteome interacting with particles, iodine-substituted BODIPY (I-BODIPY) is selected as the photosensitizer and covalently conjugated onto amino-polystyrene nanoparticles as a model system. Next, selective proximity labeling of interacting proteins is demonstrated using I-BODIPY-labeled nanoplastic particles in both Escherichia coli lysate and live alpha mouse liver 12 cells. Mechanistic studies reveal that the covalent modifications of proteins by an aminoalkyne substrate are conducted via a reactive oxygen species photosensitization pathway. Further proteomic analysis uncovers that mitochondria-related proteins are intensively involved in the protein corona, indicating substantial interactions between nanoplastic particles and mitochondria. In addition, proteostasis network components are also identified, accompanied by consequent cellular proteome aggregation confirmed by fluorescence imaging. Together, this work exemplifies a general strategy to interrogate the composition of the protein corona of nanomaterials by endowing them with photooxidation properties to enable photocatalytic protein proximity labeling function.

A Cell-Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome.

Intracellular proteome aggregation is a ubiquitous disease hallmark with its composition associated with pathogenicity. Herein, this work reports on a cell-permeable photosensitizer (P8, Rose Bengal derivative) for selective photo induced proximity labeling and crosslinking of cellular aggregated proteome. Rose Bengal is identified out of common photosensitizer scaffolds for its unique intrinsic binding affinity to various protein aggregates driven by the hydrophobic effect. Further acetylation permeabilizes Rose Bengal to selectively image, label, and crosslink aggregated proteome in live stressed cells. A combination of photo-chemical, tandem mass spectrometry, and protein biochemistry characterizations reveals the complexity in photosensitizing pathways (both Type I & II), modification sites and labeling mechanisms. The diverse labeling sites and reaction types result in highly effective enrichment and identification of aggregated proteome. Finally, aggregated proteomics and interaction analyses thereby reveal extensive entangling of proteostasis network components mediated by HSP70 chaperone (HSPA1B) and active participation of autophagy pathway in combating proteasome inhibition. Overall, this work exemplifies the first photo induced proximity labeling and crosslinking method (namely AggID) to profile intracellular aggregated proteome and analyze its interactions.

Transcriptome analysis reveals diverse Curvularia tsudae strategies in response to cadmium stress.

Cadmium (Cd) is a highly toxic heavy metal that poses significant threats to living organisms. Curvularia tsudae has demonstrated remarkable survival capabilities in the presence of high Cd concentrations, exhibiting its exceptional Cd tolerance. Although some physiological studies have been conducted, the molecular mechanisms underlying Cd tolerance in C. tsudae is largely unknown. In this study, a comparative transcriptome analysis was performed to explore the molecular mechanisms of C. tsudae under Cd stress. Among the 10,498 identified unigenes, 2526 differentially expressed genes (DEGs) were identified between the Cd-free and Cd-treated samples. Functional annotation and enrichment analysis of these DEGs identified several key biological processes involved in coping with Cd stress. Genes related to cell wall modification and organic acid metabolism contributes to Cd binding or chelation. Fourier transform infrared spectroscopy (FTIR) analysis further highlighted the modifications in functional groups with the cell wall under Cd stress. Furthermore, the transporters tended to be modulated in response to Cd stress, and up-regulated genes involved in antioxidants likely contributes to high Cd tolerance. The processes from DNA to protein metabolism appeared to responsive to the presence of Cd stress as well. These results contribute to the advance of the current knowledge about the response of C. tsudae to Cd stress and lay the foundation for further advancements in using fungi for the remediation of Cd-polluted environments.

Phosphorus/nitrogen sensing and signaling in diverse root-fungus symbioses.

Establishing mutualistic relationships between plants and fungi is crucial for overcoming nutrient deficiencies in plants. This review highlights the intricate nutrient sensing and uptake mechanisms used by plants in response to phosphate and nitrogen starvation, as well as their interactions with plant immunity. The coordination of transport systems in both host plants and fungal partners ensures efficient nutrient uptake and assimilation, contributing to the long-term maintenance of these mutualistic associations. It is also essential to understand the distinct responses of fungal partners to external nutrient levels and forms, as they significantly impact the outcomes of symbiotic interactions. Our review also highlights the importance of evolutionarily younger and newly discovered root-fungus associations, such as endophytic associations, which offer potential benefits for improving plant nutrition. Mechanistic insights into the complex dynamics of phosphorus and nitrogen sensing within diverse root-fungus associations can facilitate the identification of molecular targets for engineering symbiotic systems and developing plant phenotypes with enhanced nutrient use efficiency. Ultimately, this knowledge can inform tailored fertilizer management practices to optimize plant nutrition.

A novel cuproptosis pattern and tumor immune microenvironment characterization in urothelial carcinoma of the bladder.

Background: Urothelial carcinoma of the bladder (UCB) is the most prevalent malignant tumor of the urinary system worldwide, which has a significant recurrence rate despite multiple treatment options available. As a unique and novel copper-dependent programmed cell death mechanism, the comprehensive impact of cuproptosis on the tumor immune microenvironment, clinicopathological characteristics and the prognosis of patients remains largely unclear. Methods: A total of 568 UCB samples were thoroughly examined for cuproptosis patterns using data downloaded from TCGA and GEO, based on 10 cuproptosis-related genes reported previously. Then, the univariate COX regression analysis was performed on the genes that differed across the various patterns. To measure individual cuproptosis pattern, a cuproptosis score system was constructed using a principal component analysis algorithm. To validate the scoring system, immunohistochemical staining was performed on tumor tissues with different pathological grades, and experiments in vitro were conducted about the differentially expressed genes related to prognosis. Finally, the capacity of scoring system to predict the response to immunotherapy was verified by using data from IMvigor 210 cohort. Results: Four unique cuproptosis clusters and two gene clusters were finally found by the investigation. The clinical features and prognosis of patients, as well as the mRNA transcriptome, pathway enrichment, and immune cell infiltration in TME, varied dramatically between various cuproptosis clusters and gene clusters. To identify individual cuproptosis patterns in UCB patients, we also established a cuproptosis scoring system. After validation with multiple methods, it was indicated that the score system could predict the prognosis of UCB patients and was significantly connected to clinical features such TNM category, tumor grade, molecular type and ultimate survival status. The clinical outcomes of UCB patients were predicted effectively according to the tumor mutation burden in conjunction with the scoring system. Furthermore, we found that the cuproptosis score had a significant correlation with the response to immunotherapy and the sensitivity to chemotherapy. Conclusion: This study revealed the potential impact of cuproptosis on the UCB tumor immune microenvironment and clinical pathological characteristics. The cuproptosis score system could effectively predict the prognosis of patients and the response to chemotherapy and immunotherapy.

The expression and distribution of TACAN in human and rat bladders.

OBJECTIVES: A lot of ion channels participate in the regulation of bladder function. TACAN, a new mechanosensitive ion channel, was first discovered in 2020. TACAN has been found to be expressed in many tissues, such as the dorsal root ganglia (DRG) and adipose tissue. However, it is unclear whether or not TACAN is expressed in the bladder. In this work, we decided to study the expression and distribution of TACAN in human and rat bladders. Meanwhile, the expression of TACAN in the rat model of interstitial cystitis/bladder pain syndrome (IC/BPS) was studied. METHODS: Human bladder tissues were obtained from female patients. Cyclophosphamide (CYP) was used to build the rat model of IC/BPS. Real-time polymerase chain reaction, agarose gel electrophoresis, and western blotting were used to assess the expression of TACAN in human and rat bladders. Immunohistochemistry and immunofluorescence were used to observe the distribution of TACAN in human and rat bladders. Hematoxylin-eosin stain, withdrawal threshold, and micturition interval were used to evaluate animal models. RESULTS: The results of agarose gel electrophoresis and western blotting suggested that TACAN was expressed in human and rat bladders. Immunohistochemical results suggested that TACAN showed positive immunoreaction in the urothelial and detrusor layers. The immunofluorescence results indicated that TACAN was co-stained with UPKIII, α-SMA, and PGP9.5. The IC/BPS model was successfully established with CYP. The mRNA and protein expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. CONCLUSIONS: TACAN was found in human and rat bladders. TACAN was mainly distributed in the urothelial and detrusor layers and bladder nerves. The expression of TACAN was upregulated in the CYP-induced rat model of IC/BPS. This new discovery will provide a theoretical basis for future research on the function of TACAN in the bladder and a potential therapeutic target for IC/BPS.

Fluorene-based tau fibrillation sensor and inhibitor with fluorogenic and photo-crosslinking properties.

Tau protein aggregation into neurofibrillary tangles often causes tauopathies. Herein, we report fluorene based sensors with fluorogenicity upon binding to tau proteins. Intriguingly, these sensors possess triplet state properties to inhibit tau fibrillation upon photo-induced crosslinking.

Chemoselective cycloisomerization of O-alkenylbenzamides via concomitant 1,2-aryl migration/elimination mediated by hypervalent iodine reagents.

As an ambident nucleophile, controlling the reaction selectivities of nitrogen and oxygen atoms in amide moiety is a challenging issue in organic synthesis. Herein, we present a chemodivergent cycloisomerization approach to construct isoquinolinone and iminoisocoumarin skeletons from o-alkenylbenzamide derivatives. The chemo-controllable strategy employed an exclusive 1,2-aryl migration/elimination cascade, enabled by different hypervalent iodine species generated in situ from the reaction of iodosobenzene (PhIO) with MeOH or 2,4,6-tris-isopropylbenzene sulfonic acid. DFT studies revealed that the nitrogen and oxygen atoms of the intermediates in the two reaction systems have different nucleophilicities and thus produce the selectivity of N or O-attack modes.

High precision structured H∞ control of a piezoelectric nanopositioning platform.

The inherent weakly damped resonant modes of the piezoelectric nanopositioning platform and the presence of model uncertainty seriously affect the performance of the system. A structured H∞ design is used in this paper to solve the accuracy and robustness problems respectively using a two-loop control structure. The multiple performance requirements of the system are constituted into an H∞ optimization matrix containing multi-dimensional performance diagonal decoupling outputs, and an inner damping controller d is set according to the damping of the resonant modes; the second-order robust feedback controller is preset in the inner loop to improve the robustness of the system; the tracking controller is connected in series in the outer loop to achieve high accuracy scanning; finally, the structured H∞ controller is designed to meet the multiple performance requirements. To verify the effectiveness of the proposed structured H∞ control, simulation comparison experiments are done with the integral resonant control (IRC) and H∞ controller. The results demonstrate that the designed structured H∞ controller achieves higher tracking accuracy compared to the IRC and H∞ controllers under grating input signals of 5, 10, and 20 Hz. Moreover, it has good robustness under 600g and 1000g loads and high frequency disturbances close to the resonant frequency of the system, meeting multiple performance requirements. Compared with the traditional H∞ control, yet with lower complexity and transparency, which is more suitable for engineering practice applications.

Agronomic Investigation of Spray Dispersion of Metal-Based Nanoparticles on Sunflowers in Real-World Environments.

In environmental and agronomic settings, even minor imbalances can trigger a range of unpredicted responses. Despite the widespread use of metal-based nanoparticles (NPs) and new bio-nanofertilizers, their impact on crop production is absent in the literature. Therefore, our research is focused on the agronomic effect of spray application of gold nanoparticles anchored to SiO2 mesoporous silica (AuSi-NPs), zinc oxide nanoparticles (ZnO-NPs), and iron oxide nanoparticles (Fe3O4-NPs) on sunflowers under real-world environments. Our findings revealed that the biosynthetically prepared AuSi-NPs and ZnO-NPs were highly effective in enhancing sunflower seasonal physiology, e.g., the value of the NDVI index increased from 0.012 to 0.025 after AuSi-NPs application. The distribution of leaf trichomes improved and the grain yield increased from 2.47 t ha-1 to 3.29 t ha-1 after ZnO-NPs application. AuSi-NPs treatment resulted in a higher content of essential linoleic acid (54.37%) when compared to the NPs-free control (51.57%), which had a higher determined oleic acid. No NPs or residual translocated metals were detected in the fully ripe sunflower seeds, except for slightly higher silica content after the AuSi-NPs treatment. Additionally, AuSi-NPs and NPs-free control showed wide insect biodiversity while ZnO-NPs treatment had the lowest value of phosphorus as anti-nutrient. Contradictory but insignificant effect on physiology, yield, and insect biodiversity was observed in Fe3O4-NPs treatment. Therefore, further studies are needed to fully understand the long-term environmental and agricultural sustainability of NPs applications.

Evaluation of sediment dredging in remediating toxic metal contamination - a systematic review.

Toxic metal pollution is a leading environmental concern for aquatic systems globally, and remedial dredging has been widely employed to mitigate its harmful impacts. In terms of the short-term impacts of remedial dredging, mixed results are reported in several studies. Despite its immediate negative impacts including saturation of water with toxic metals, increased turbidity, and sediment resuspension, positive impacts can be recorded over a stabilization period of 6-24 months after dredging. Nevertheless, the sustainability of these recorded positive effects cannot be ascertained as some studies have reported long-term regression in remediated sites' conditions. Evaluation of success determinants, site-measure compatibility, and determination of supplementary measures are keys to achieving and sustaining the projected benefits of remedial dredging and justifying its overall cost. This multicomponent study reviewed published literatures that documented the outcomes of short- and long-term dredging projects in toxic metal-polluted systems globally with a broad goal of examining how sediment removal impacts toxic metal dynamics in the aquatic system and understanding why the sustenance of positive impacts is controversial. In the meantime, this study also explored the preventative and remedial management strategies for attaining and sustaining positive dredging outcomes. The purpose of this study is to provide key recommendations for decision-making and policy development in aquatic toxic metal remediation.

Circular RNA EPHA3 suppresses progression and metastasis in prostate cancer through the miR-513a-3p/BMP2 axis.

BACKGROUND: Circular RNAs (circRNAs) may regulate the onset and progression of human malignancies by competitively binding to microRNA (miRNA) sponges, thus regulating the downstream genes. However, aberrant circRNA expression patterns and their biological functions in prostate cancer (PCa) warrant further studies. Our research sought to shed further light on the possible role and molecular mechanism of circEPHA3 action in controlling the growth and metastasis of PCa cells. MATERIALS AND METHODS: circEPHA3 (has_circ_0066596) was initially screened from a previous circRNA microarray and identified following Actinomycin D and RNase R assays. Fluorescence in situ hybridization, biotin-coupled probe RNA pulldown, and dual-luciferase reporter gene assays were performed to examine the relationship between circEPHA3 and miR-513a-3p. The biological role of circEPHA3 in PCa was assessed by CCK8, wound healing, Transwell assays, and animal experiments. RESULTS: We identified a novel circular RNA, circEPHA3 (has_circ_0066596), which was down-regulated in high-grade PCa tissues and cell lines. The outcomes of CCK8, wound healing, Transwell assays, and animal experiments revealed that circEPHA3 prohibited the progression and metastasis of PCa in vivo and in vitro. Mechanistically, circEPHA3 was directly bound to miR-513a-3p and regulated the downstream gene, BMP2, thereby serving as a tumor suppressor in PCa. CONCLUSIONS: As a tumor suppressor, circEPHA3 inhibited the proliferation and metastasis of PCa cells through the miR-513a-3p/BMP2 axis, suggesting that circEPHA3 might be a potential therapeutic target for PCa.

Stereospecific Dehydroxytrifluoromethylthiolation of Alcohols Promoted by a Combination of Hypervalent Trifluoromethylthio-iodine(III) Reagent and N-Heterocyclic Carbene.

Direct dehydroxytrifluoromethylthiolation of alcohols is an attractive strategy for accessing CF3S-containing compounds. Herein, we report a method for dehydroxytrifluoromethylthiolation of alcohols by using the combination of hypervalent iodine(III) reagent TFTI and N-heterocyclic carbenes. This method shows excellent stereospecificity and chemoselectivity to give a product with clean inversion of the configuration of hydroxyl groups as well as can be used for late-stage modification of structurally complex alcohols. The reaction mechanism is proposed with experimental and computational evidence.

A patent review of EZH2 inhibitors from 2017 and beyond.

INTRODUCTION: EZH2 is an important epigenetic regulator that forms the PRC2 complex with SUZ12, EED and RbAp46/48. As the key catalytic subunit of PRC2, EZH2 regulates the trimethylation of histone H3K27, which in turn promotes chromatin condensation and represses the transcription of relevant target genes. EZH2 overexpression and mutations are strictly related to tumor proliferation, invasion and metastasis. Currently, a large number of highly specific EZH2 inhibitors have been developed and some have already been in clinical trials. AREAS COVERED: The aim of the present review is to provide an overview of the molecular mechanisms of EZH2 inhibitors and to highlight the research advances in the patent literature published from 2017 to date. A search of the literature and patents for EZH2 inhibitors and degraders was performed using the Web of Science, SCIFinder, WIPO, USPTO, EPO and CNIPA databases. EXPERT OPINION: In recent years, a great number of structurally diverse EZH2 inhibitors have been identified, including EZH2 reversible inhibitors, EZH2 irreversible inhibitors, EZH2-based dual inhibitors and EZH2 degraders. Despite the multiple challenges, EZH2 inhibitors offer promising potential for the treatment of various diseases, such as cancers.

Estimation of nutrient (N and P) fluxes into Newark Bay, USA.

This study was conducted in northern New Jersey, USA, to estimate the nutrient fluxes from the Passaic River, the Hackensack River and other sources into Newark Bay and the nutrient residence time in Newark Bay. Bi-weekly total inorganic nitrogen (TIN) and orthophosphate concentration data in the Passaic River, the Hackensack River, and Newark Bay for over 15 years (2004-2019) were collected along with daily river discharge data from the public database. The annual TIN and orthophosphate (ortho-P) loading from the Passaic River ranged from 915 × 103 kg y-1 to 251 × 104 kg y-1 and 94 × 103 kg y-1to 372 × 103 kg y-1, respectively. The annual TIN and ortho-P loading from the Hackensack River ranged from 3.13 × 103 kg y-1 to 234 × 103 kg y-1 and 0.28 × 103 kg y-1 to 6.97 × 103 kg y-1, respectively. Seasonal variation results indicated that hurricane events highly increased TIN and ortho-P loading from riverine input and reduced residence time in Newark Bay.

Erectile dysfunction and exosome therapy.

Erectile dysfunction (ED), as a common male disease, can seriously reduce the life quality of men and their partners. With the improvement of human living standards, ED is considered to be an important health issue that plagues men. However, it is difficult for existing therapeutic approaches to meet the needs of all patients, so it is necessary to develop novel treatment strategies. Exosomes, as a class of vesicles secreted by cells with bilayer membrane structure, are involved in various physiological and pathological processes in human body and considered to have great therapeutic potentials. This review summarizes the recent advances on exosome therapy with animal models of ED, and proposes the prospect of future research in order to provide a basis for clinical trials and clinical translation.

Downregulation of CAMK2N1 due to DNA Hypermethylation Mediated by DNMT1 that Promotes the Progression of Prostate Cancer.

Calcium/calmodulin-dependentprotein kinase II inhibitor I (CAMK2N1) as one of the tumor suppressor genes is significantly downregulated in prostate cancer (PCa). Reduced expression of CAMK2N1 is positively correlated with PCa progression. However, the mechanisms of CAMK2N1 downregulation in PCa are still unclear. The promoter region of CAMK2N1 contains a large number of CG loci, providing the possibility for DNA methylation. Consequently, we hypothesized that DNA methylation can result in the reduced expression of CAMK2N1 in PCa. In the presented study, the DNA methylation level of CAMK2N1 in prostate cells and clinical specimens was determined by bisulfite sequencing (BS), pyrosequencing, and in silico analysis. Results showed that CAMK2N1 was highly methylated in PCa cells and tissues compared to normal prostate epithelial cells and nonmalignant prostate tissues, which was associated with the clinicopathological characteristics in PCa patients. Afterwards, we explored the expression of CAMK2N1 and its DNA methylation level by qRT-PCR, western blot, BS, and methylation-specific PCR in PCa cells after 5-Aza-CdR treatment or DNMT1 genetic modification, which demonstrated that the reduced expression of CAMK2N1 can be restored by 5-Aza-CdR treatment via demethylation. Moreover, DNMT1 formed a positive feedback loop with CAMK2N1 in PCa cells. The expression of CAMK2N1 was downregulated by DNMT1-mediated DNA methylation, which reversely induced DNMT1 expression through activating AKT or ERK signaling pathway. Finally, functional assays including wound healing, invasion, and migration assay, as well as the xenograft model in nude mice indicated that CAMK2N1 inhibited the invasion, migration, and proliferation of PCa cells and these effects were reversed by DNMT1 overexpression. In conclusion, DNMT1-mediated hypermethylation of CAMK2N1 not only downregulates the gene expression but also promotes the progression of PCa.