Association between type 2 diabetes, alcohol intake frequency, age at menarche, and gallbladder cancer: a two-sample Mendelian randomization study.

Background: Gallbladder cancer (GBC) is a rare malignancy of the digestive tract, characterized by a remarkably poor prognosis. Currently, there is a controversy on the relationship between type 2 diabetes (T2D) and GBC. Additionally, no definitive conclusions were established regarding the causal relationships between alcohol intake frequency (AIF), age at menarche (AAM) and GBC. The objective of this study was to elucidate the causal association between T2D, AIF, AAM, and GBC. Methods: Single-nucleotide polymorphisms (SNPs) associated with exposures and outcomes were sourced from the Integrative Epidemiology Unit (IEU) Open Genome-Wide Association Study (GWAS) database. Specifically, the data of GBC comprised 907 East Asians (pathological results of all cases were registered into Biobank Japan) and 425,707 SNPs; T2D comprised 655,666 Europeans with 5,030,727 SNPs; AIF comprised 462,346 Europeans and 9,851,867 SNPs; AAM comprised 243,944 Europeans and 9,851,867 SNPs. The measurement of exposure traits is collected uniformly from the UK Biobank (UKB) database and presented in the form of standard deviation (SD) or the logarithmic form of the odds ratio (logOR). We employed a two-sample Mendelian randomization (MR) analysis to discern the causalities between T2D, AIF, AAM, and GBC. Sensitivity analyses were conducted to identify and address potential heterogeneity, horizontal pleiotropy, and outliers. Results: Our findings indicated that T2D reduced GBC risk [odds ratio (OR) =0.044; 95% confidence interval (CI): 0.004-0.55; P=0.015, inverse variance-weighted (IVW)]. However, no causal relationship was observed between AIF (OR =0.158; 95% CI: 5.33E-05 to 466.84; P=0.65, IVW), AAM (OR =0.19; 95% CI: 0.0003-140.34; P=0.62, IVW), and GBC. Sensitivity analysis revealed no evidence of horizontal pleiotropy, heterogeneity, or outliers, suggesting the robustness and reliability of our conclusions. Conclusions: T2D emerged as a potentially protective factor against GBC, whereas neither AIF nor AAM demonstrated a causal relationship with GBC risk. Regulation of glucose metabolism may be one of the methods for preventing GBC.

Transcobalamin 2 orchestrates monocyte proliferation and TLR4-driven inflammation in systemic lupus erythematosus via folate one-carbon metabolism.

Background: SLE is a complex autoimmune disease with deleterious effects on various organs. Accumulating evidence has shown abnormal vitamin B12 and one-carbon flux contribute to immune dysfunction. Transcobalamin II (TCN2) belongs to the vitamin B12-binding protein family responsible for the cellular uptake of vitamin B12. The role of TCN2 in SLE is still unclear. Methods: We collected clinical information and blood from 51 patients with SLE and 28 healthy controls. RNA sequencing analysis, qPCR, and western blot confirmed the alteration of TCN2 in disease monocytes. The correlation between TCN2 expression and clinical features and serological abnormalities was analyzed. TCN2 heterozygous knockout THP1 cells were used to explore the effects of TCN2 dysfunction on monocytes. CCK-8 assay and EdU staining were used to detect cell proliferation. ELISA was conducted to assess vitamin B12, glutathione, and cytokines changes. UHPLC-MRM-MS/MS was used to detect changes in the intermediates of the one-carbon cycle. Flow cytometry is used to detect cell cycle, ROS, mitoROS, and CD14 changes. Results: Elevated TCN2 in monocytes was correlated positively with disease progression and specific tissue injuries. Using CD14+ monocytes and TCN2 genetically modified THP1 cell lines, we found that the TCN2 was induced by LPS in serum from SLE patients. TCN2 heterozygous knockout inhibited cellular vitamin B12 uptake and one-carbon metabolism, leading to cell proliferation arrest and decreased Toll-like receptor 4 (TLR4)-mediated CCL2 release. Methionine cycle metabolites, s-adenosylmethionine and homocysteine, rescued these effects, whereas folate treatment proved to be ineffective. Folate deficiency also failed to replicate the impact of TCN2 downregulation on THP1 inflammatory response. Conclusion: Our study elucidated the unique involvement of TCN2-driven one-carbon flux on SLE-associated monocyte behavior. Increased TCN2 may promote disease progression and tissue damage by enhancing one-carbon flux, fostering monocyte proliferation, and exacerbating TLR4 mediated inflammatory responses. The inhibition of TCN2 may be a promising therapeutic approach to ameliorate SLE.

Photoinduced Selective B-H Activation of nido-Carboranes.

The development of new synthetic methods for B-H bond activation has been an important research area in boron cluster chemistry, which may provide opportunities to broaden the application scope of boron clusters. Herein, we present a new reaction strategy for the direct site-selective B-H functionalization of nido-carboranes initiated by photoinduced cage activation via a noncovalent cage···π interaction. As a result, the nido-carborane cage radical is generated through a single electron transfer from the 3D nido-carborane cage to a 2D photocatalyst upon irradiation with green light. The resulting transient nido-carborane cage radical could be directly probed by an advanced time-resolved EPR technique. In air, the subsequent transformations of the active nido-carborane cage radical have led to efficient and selective B-N, B-S, and B-Se couplings in the presence of N-heterocycles, imines, thioethers, thioamides, and selenium ethers. This protocol also facilitates both the late-stage modification of drugs and the synthesis of nido-carborane-based drug candidates for boron neutron capture therapy (BNCT).

Efficacy and safety of 1565-nm nonablative fractional laser combined with mucopolysaccharide polysulfate cream for erythematous acne scars.

PURPOSE: To evaluate the efficacy and safety of 1565-nm nonablative fractional laser (NAFL) combined with mucopolysaccharide polysulfate (MPS) cream in the treatment of erythematous acne scars. METHODS: A total of 28 subjects with erythematous acne scars from June 2021 to April 2022 were enrolled. One side of each subject's face was randomly assigned to be treated with 1565-nm NAFL (at 2 sessions with four-week intervals) combined with MPS cream (twice daily) for 8 weeks, and the other side with 1565-nm NAFL combined with placebo cream. CBS® images and parameters, dermoscopic images and the quantitative data processed by ImageJ software, and quantitative global scarring grading system (GSS) score were obtained at baseline and after treatment. Subjects' satisfaction assessment was performed after treatment. Adverse events were recorded during treatment. RESULTS: In CBS® parameters, the red area, red area concentration, and smoothness were improved more significantly on the 1565-nm NAFL combined with MPS cream side than on the 1565-nm NAFL combined with placebo cream side after treatment (p = 0.015, p = 0.013, and p = 0.021). For dermoscopy, both scar area and scar redness achieved a significantly greater percentage of improvement on the side of 1565-nm NAFL combined with MPS cream than the side of 1565-nm NAFL combined with placebo cream after treatment (p = 0.005 and p = 0.041). The reduction of quantitative GSS score and Subjects' satisfaction assessment were similarly superior on the 1565-nm NAFL combined with MPS cream side. Temporary erythema was experienced by all subjects after each 1565-nm NAFL treatment. No subject reported intolerance or allergy to the cream during follow-up. CONCLUSIONS: The combined application of 1565-nm NAFL and MPS cream could be an effective and safe treatment for erythematous acne scars. ImageJ software enables quantitative evaluation of dermoscopic images of acne scars.

Direct B-H Functionalization of Icosahedral Carboranes via Hydrogen Atom Transfer.

The efficient and selective functionalization of icosahedral carboranes (C2B10H12) at the boron vertexes is a long-standing challenge owing to the presence of 10 inert B-H bonds in a similar chemical environment. Herein, we report a new reaction paradigm for direct B-H functionalization of icosahedral carboranes via B-H homolysis enabled by a nitrogen-centered radical-mediated hydrogen atom transfer (HAT) strategy. Both the HAT process of the carborane B-H bond and the resulting boron-centered carboranyl radical intermediate have been confirmed experimentally. The reaction occurs at the most electron-rich boron vertex with the lowest B-H bond dissociation energy (BDE). Using this strategy, diverse carborane derivatization, including thiolation, selenation, alkynylation, alkenylation, cyanation, and halogenation, have been achieved in satisfactory yields under a photoinitiated condition in a metal-free and redox-neutral fashion. Moreover, the synthetic utility of the current protocol was also demonstrated by both the scale-up reaction and the construction of carborane-based functional molecules. Therefore, this methodology opens a radical pathway to carborane functionalization, which is distinct from the B-H heterolytic mechanism in the traditional strategies.

Stereospecific nickel-catalyzed [4+2] heteroannulation of alkynes with aminophosphanes.

Enantioenriched phosphorus compounds play crucial roles in many fields ranging from catalyst to materials science to drug development. Despite advances in the construction of phosphacycles, incorporation of a P-chirogenic center into heterocycles remains challenging. Here, we report an effective method for the preparation of phosphacycles through nickel-catalyzed [4+2] heteroannulation of internal alkynes with aminophosphanes derived from o-haloanilines. Notably, chiral 2-λ5-phosphaquinolines can be prepared from P-stereogenic substrates via NH/PH tautomeric equilibrium without loss of stereochemical integrity. The strategy is found to exhibit a broad scope in terms of both reaction components, enabling modular construction of libraries of 2-λ5-phosphaquinolines with different steric and electronic properties for fine-tuning photophysical properties, where some of these compounds showed distinct fluorescence with high quantum yields. A series of mechanistic studies further shed light on the pathway of the heteroannulation and reasons for stereospecificity.

Research Progress of Cell Lineage Tracing and Single-Cell Sequencing Technology in Malignant Skin Tumors.

Cell lineage tracing and single-cell sequencing have been widely applied in development biology and oncology to reveal the molecular mechanisms in multiple basic biological processes and the differentiation of stem cells, as well as quantify the differences between single cells. They provide new methods for in-depth understanding of the origin of tumors, the heterogeneity of tumor cells, and the drug resistance mechanism of tumors, thus inspiring new strategies for tumor treatment. In this review, we summarized the progress of cell lineage tracing technology and single-cell sequencing technology in the research of malignant melanoma and cutaneous squamous cell carcinoma, attempting to spark new ideas for further research on skin tumors.

Single-Cell Transcriptional Analysis Deciphers the Inflammatory Response of Skin-Resident Stromal Cells.

The skin is the outermost barrier of the body. It has developed a sophisticated system against the ever-changing environment. The application of single-cell technologies has revolutionized dermatology research and unraveled the changes and interactions across skin resident cells in the healthy and inflamed skin. Single-cell technologies have revealed the critical roles of stromal cells in an inflammatory response and explained a series of plausible previous findings concerning skin immunity. Here, we summarized the functional diversity of skin stromal cells defined by single-cell analyses and how these cells orchestrated events leading to inflammatory diseases, including atopic dermatitis, psoriasis, vitiligo, and systemic lupus erythematosus.

Single-Cell RNA Sequencing Unravels Upregulation of Immune Cell Crosstalk in Relapsed Pediatric Ependymoma.

Ependymoma (EPN) is a malignant glial tumor occurring throughout central nervous system, which commonly presents in children. Although recent studies have characterized EPN samples at both the bulk and single-cell level, intratumoral heterogeneity across subclones remains a confounding factor that impedes understanding of EPN biology. In this study, we generated a high-resolution single-cell dataset of pediatric ependymoma with a particular focus on the comparison of subclone differences within tumors and showed upregulation of cilium-associated genes in more highly differentiated subclone populations. As a proxy to traditional pseudotime analysis, we applied a novel trajectory scoring method to reveal cellular compositions associated with poor survival outcomes across primary and relapsed patients. Furthermore, we identified putative cell-cell communication features between relapsed and primary samples and showed upregulation of pathways associated with immune cell crosstalk. Our results revealed both inter- and intratumoral heterogeneity in EPN and provided a framework for studying transcriptomic signatures of individual subclones at single-cell resolution.

Palladium-Catalyzed Hydroboration of Alkynes with Carboranes: Facile Construction of a Library of Boron Cluster-Based AIE-Active Luminogens.

The classical aggregation-induced emission (AIE)-active luminogens (AIEgens) usually include two-dimensional aromatic systems such as tetraphenylethenes, which are synthesized in several steps by using toxic additives. Here, we proposed a new molecular design strategy for the realization of AIE properties by combining three-dimensional aromatic boron clusters of carboranes with vinyl group(s). To obtain a library of the boron cluster-based AIEgens, a Pd-catalyzed hydroboration of alkynes with carboranes is reported. This reaction protocol proceeds in one step under mild conditions with rapid reaction rate, excellent yields and regioselectivity. Photophysical property studies demonstrate that the facile molecular motions in solution can be inhibited in the solid state for these molecules, which leads to interesting AIE properties. This work provides not only a general design principle for AIEgens but also an efficient methodology to synthesize boron cluster-based photo-functional molecules.

Site-Selective Functionalization of Carboranes at the Electron-Rich Boron Vertex: Photocatalytic B-C Coupling via a Carboranyl Cage Radical.

Functionalization of carboranes in a vertex-specific manner is a perennial challenge. Here, we report a photocatalytic B-C coupling for the selective functionalization of carboranes at the boron site which is most distal to carbon. This reaction was achieved by the photo-induced decarboxylation of carborane carboxylic acids to generate boron vertex-centered carboranyl radicals. Theoretical calculations also demonstrate that the reaction more easily occurs at the boron site bearing higher electron density owing to the lower energy barrier for a single-electron transfer to generate a carboranyl radical. By using this strategy, a number of functionalized carboranes could be accessed through alkylation, alkenylation, and heteroarylation under mild conditions. Moreover, both a highly efficient blue emitter with a solid-state luminous efficiency of 42 % and a drug candidate for boron neutron capture therapy (BNCT) containing targeting and fluorine units were obtained.

Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle.

BACKGROUND: Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis. METHODS: Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq). RESULTS: TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation. CONCLUSION: TPCN2 might be a potential protective factor against SLE.

rs12537 Is a Novel Susceptibility SNP Associated With Estrogen Receptor Positive Breast Cancer in Chinese Han Population.

Genetic testing is widely used in breast cancer and has identified a lot of susceptibility genes and single nucleotide polymorphisms (SNPs). However, for many SNPs, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are not in place. A recent genome-wide long non-coding RNA (lncRNA) association study in Chinese Han has verified a genetic association between rs12537 and breast cancer. This study is aimed at investigating the association between rs12537 and the phenotype. We collected the clinical information of 5,634 breast cancer patients and 6,308 healthy controls in the early study. And χ2 test was used for the comparison between different groups in genotype. The frequency of genotypic distribution among SNP rs12537 has no statistically significant correlation with family history (p = 0.8945), menopausal status (p = 0.3245) or HER-2 (p = 0.2987), but it is statistically and significantly correlated with ER (p = 0.004006) and PR (p = 0.01379). Most importantly, compared to the healthy control, rs12537 variant is significantly correlated with ER positive patients and the p-value has reached the level of the whole genome (p = 1.66E-08 <5.00E-08). Furthermore, we found rs12537 associated gene MTMR3 was lower expressed in breast cancer tissues but highly methylated. In conclusion, our findings indicate that rs12537 is a novel susceptibility gene in ER positive breast cancer in Chinese Han population and it may influence the methylation of MTMR3.

Photoredox B-H functionalization to selective B-N(sp3) coupling of nido-carborane with primary and secondary amines.

Access to nido-carborane site-selective B-N(sp3) coupling by photoredox catalysed B-H activation has been achieved for the first time, which leads to the synthesis of a series of nitrogen-containing nido-carboranes with moderate to good yields. This protocol is applicable to primary and secondary amines containing alkyl, or heteroaryl groups as well as sulfonamides. Furthermore, the open to air and metal-free conditions with excellent site-selectivity represent a significant improvement for B-H functionalization of nido-carboranes with organic functionalities.

Genome-wide long non-coding RNA association study on Han Chinese women identifies lncHSAT164 as a novel susceptibility gene for breast cancer.

BACKGROUND: Single-nucleotide polymorphisms (SNPs)-associated genes and long non-coding RNAs (lncRNAs) can contribute to human disease. To comprehensively investigate the contribution of lncRNAs to breast cancer, we performed the first genome-wide lncRNA association study on Han Chinese women. METHODS: We designed an lncRNA array containing >800,000 SNPs, which was incorporated into a 96-array plate by Affymetrix (CapitalBio Technology, China). Subsequently, we performed a two-stage genome-wide lncRNA association study on Han Chinese women covering 11,942 individuals (5634 breast cancer patients and 6308 healthy controls). Additionally, in vitro gain or loss of function strategies were performed to clarify the function of a novel SNP-associated gene. RESULTS: We identified a novel breast cancer-associated susceptibility SNP, rs11066150 (Pmeta = 2.34 × 10-8), and a previously reported SNP, rs9397435 (Pmeta = 4.32 × 10-38), in Han Chinese women. rs11066150 is located in NONHSAT164009.1 (lncHSAT164), which is highly expressed in breast cancer tissues and cell lines. lncHSAT164 overexpression promoted colony formation, whereas lncHSAT164 knockdown promoted cell apoptosis and reduced colony formation by regulating the cell cycle. CONCLUSIONS: Based on our lncRNA array, we identified a novel breast cancer-associated lncRNA and found that lncHSAT164 may contribute to breast cancer by regulating the cell cycle. These findings suggest a potential therapeutic target in breast cancer.

Hypothalamic Rax+ tanycytes contribute to tissue repair and tumorigenesis upon oncogene activation in mice.

Hypothalamic tanycytes in median eminence (ME) are emerging as a crucial cell population that regulates endocrine output, energy balance and the diffusion of blood-born molecules. Tanycytes have recently been considered as potential somatic stem cells in the adult mammalian brain, but their regenerative and tumorigenic capacities are largely unknown. Here we found that Rax+ tanycytes in ME of mice are largely quiescent but quickly enter the cell cycle upon neural injury for self-renewal and regeneration. Mechanistically, Igf1r signaling in tanycytes is required for tissue repair under injury conditions. Furthermore, Braf oncogenic activation is sufficient to transform Rax+ tanycytes into actively dividing tumor cells that eventually develop into a papillary craniopharyngioma-like tumor. Together, these findings uncover the regenerative and tumorigenic potential of tanycytes. Our study offers insights into the properties of tanycytes, which may help to manipulate tanycyte biology for regulating hypothalamic function and investigate the pathogenesis of clinically relevant tumors.

Electrooxidative B-H Functionalization of nido-Carboranes.

An atom-economical method for the direct B-H functionalization of nido-carboranes (7,8-nido-C2 B9 H12 - ) has been developed under electrochemical reaction conditions. In this reaction system, anodic oxidation serves as a green alternative for traditional chemical oxidants in the oxidation of nido-carboranes. No transition-metal catalyst is required and different heteroatoms bearing a lone pair are reactive in this transformation. Coupling nido-carboranes with thioethers, selenides, tellurides, N-heterocycles, phosphates, phosphines, arsenides and antimonides demonstrates high site-selectivity and efficiency. Importantly, nido-carboranes can be easily incorporated into drug motifs through this reaction protocol.

Knockdown of NAA25 Suppresses Breast Cancer Progression by Regulating Apoptosis and Cell Cycle.

NAA25 gene variants were reported as risk factors for type 1 diabetes, rheumatoid arthritis and acute arterial stroke. But it's unknown whether it could contribute to breast cancer. We identified rs11066150 in lncHSAT164, which contributes to breast cancer, in our earlier genome-wide long non-coding RNA association study on Han Chinese women. However, rs11066150 A/G variant is also located in NAA25 intron. Based on the public database, such as TCGA and Curtis dataset, NAA25 gene is highly expressed in breast cancer tissues and this result has also been proved in our samples and cell lines through RT-qPCR and western blot analysis. To better understand the function of NAA25 in breast cancer, we knocked down the expression of NAA25 in breast cancer cell lines, FACS was used to detect cell apoptosis and cell cycle and colony formation assay was used to detect cell proliferation. We found that NAA25-deficient cells could increase cell apoptosis, delay G2/M phase cell and decrease cell clone formation. RNA sequencing was then applied to analyze the molecular profiles of NAA25-deficient cells, and compared to the control group, NAA25 knockdown could activate apoptosis-related pathways, reduce the activation of tumor-associated signaling pathways and decrease immune response-associated pathways. Additionally, RT-qPCR was employed to validate these results. Taken together, our results revealed that NAA25 was highly expressed in breast cancer, and NAA25 knockdown might serve as a therapeutic target in breast cancer.

Association of the Polymorphism rs13259960 in SLEAR With Predisposition to Systemic Lupus Erythematosus.

OBJECTIVE: Genome-wide association studies have identified many susceptibility loci for systemic lupus erythematosus (SLE). However, most of these loci are located in noncoding regions of the genome. Long noncoding RNAs (lncRNAs) are pervasively expressed and have been reported to be involved in various diseases. This study aimed to explore the genetic significance of lncRNAs in SLE. METHODS: A genome-wide survey of SLE risk variants in lncRNA gene loci was performed in Han Chinese subjects (4,556 with SLE and 9,451 healthy controls). The functional relevance of an SLE risk variant in one of the lncRNA genes was explored using biochemical and molecular cell biology analyses. In vitro loss-of-function and gain-of-function strategies were used to clarify the functional and phenotypic relevance of this SLE susceptibility lncRNA. Moreover, correlation of this lncRNA with the degree of apoptosis in the peripheral blood of SLE patients was evaluated. RESULTS: A novel SLE susceptibility locus in a lncRNA gene, designated SLEAR (for SLE-associated RNA), was identified at the single-nucleotide polymorphism rs13259960 (odds ratio 1.35, Pcombined = 1.03 × 10-11 ). The A>G variation at rs13259960, located in an intronic enhancer, was found to impair STAT1 recruitment to the enhancer that loops to the SLEAR promoter, resulting in decreased SLEAR production in peripheral blood mononuclear cells from patients with SLE (3 with the G/G genotype, 22 with A/G, and 103 with A/A at rs13259960; P = 0.0241). Moreover, SLEAR interacted with the RNA binding proteins interleukin enhancer binding factor 2, heterogeneous nuclear RNP F, and TATA-binding protein-associated factor 15, to form a complex for transcriptional activation of the downstream antiapoptotic genes. In addition, SLEAR regulated apoptosis of Jurkat cells in vitro, and its expression level was correlated with the degree of cell death in the peripheral blood of patients with SLE (r = 0.824, P = 2.15 × 10-8 ; n = 30). CONCLUSION: These findings suggest a mechanism by which the risk variant at rs13259960 modulates SLEAR expression and confers a predisposition to SLE. Taken together, these results may give insights into the etiology of SLE.

Molecular profiling of TOX-deficient neoplastic cells in cutaneous T cell lymphoma.

Cutaneous T cell lymphoma (CTCL) is a rare but potentially devastating primary cutaneous lymphoma. CTCL is characterized by localization of neoplastic T lymphocytes to the skin, with mycosis fungoides (MF) and its leukemic form, Sézary syndrome (SS) being the most common variants. Thymocyte selection-associated high-mobility group box (TOX) gene has been found to be highly expressed in MF and SS. It is reported that higher expression levels of TOX in patients will increase risks of disease progression and poor prognosis. However, the molecular events leading to these abnormalities have not been well understood. To better understand the molecular mechanism underlying TOX-mediated differentially expressed genes (DEGs) in CTCL, and to identify DEGs pathways triggered after knockdown of TOX gene in the CTCL cell line Hut78, we employed two shRNA-mediated lentiviruses to knock down TOX gene in the skin lymphoma cell line HuT78. RNA sequencing (RNAseq) analysis was applied to analyze DEGs, DEGs GO and their corresponding pathways. Knockdown of TOX can induce upregulation of 547 genes and downregulation of 649 genes, respectively. HOXC9 was the most significant downregulated gene. Most DEGs are enriched in malignancies and relate to the Wnt and mTOR signaling pathways, and therefore they can regulate cellular processes and induce different biological regulation. Transcriptome analysis of DEGs after knockdown of TOX in our study provides insights into the mechanism of TOX in CTCL and suggests candidate targets for therapy of CTCL.