RAVAR: a curated repository for rare variant-trait associations.

Rare variants contribute significantly to the genetic causes of complex traits, as they can have much larger effects than common variants and account for much of the missing heritability in genome-wide association studies. The emergence of UK Biobank scale datasets and accurate gene-level rare variant-trait association testing methods have dramatically increased the number of rare variant associations that have been detected. However, no systematic collection of these associations has been carried out to date, especially at the gene level. To address the issue, we present the Rare Variant Association Repository (RAVAR), a comprehensive collection of rare variant associations. RAVAR includes 95 047 high-quality rare variant associations (76186 gene-level and 18 861 variant-level associations) for 4429 reported traits which are manually curated from 245 publications. RAVAR is the first resource to collect and curate published rare variant associations in an interactive web interface with integrated visualization, search, and download features. Detailed gene and SNP information are provided for each association, and users can conveniently search for related studies by exploring the EFO tree structure and interactive Manhattan plots. RAVAR could vastly improve the accessibility of rare variant studies. RAVAR is freely available for all users without login requirement at http://www.ravar.bio.

Polysaccharides from sea buckthorn (Hippophae rhamnoides L.) berries ameliorate cognitive dysfunction in AD mice induced by a combination of d-gal and AlCl3 by suppressing oxidative stress and inflammation reaction.

BACKGROUND: The therapeutic properties of Hippophae rhamnoides L. were known in Ancient Greece and in Tibetan and Mongolian medicine, which commonly used it for the treatment of heart ailments, rheumatism, and brain disorders. Modern studies have indicated that Hippophae rhamnoides L. polysaccharide (HRP) can improve cognitive impairment in mice with Alzheimer's disease (AD) but the specific mechanisms of the protective effect of HRP have not been elucidated fully. RESULTS: Our results showed that Hippophae rhamnoides L. polysaccharide I (HRPI) improved pathological behaviors related to memory and cognition, and reduced 1 Beta-amyloid (Aß) peptide deposition and neuronal cell necrosis. Pretreatment with Hippophae rhamnoides L. polysaccharide I (HRPI) also decreased the level of Toll-like receptor 4 (TLR4) and Myeloid differentiation factor 88 (MyD88), and reduced the release of inflammatory factors Tumor necrosis factor alpha (TNFα) and interleukin 6 (IL-6) in the brains of mice with AD. Treatment with HRPI also suppressed the expression level of Recombinant Kelch Like ECH Associated Protein 1 (KEAP1), and increased the levels of Nuclear factor erythroid 2-Related Factor 2 (Nrf2), antioxidant enzymes Superoxide dismutase (SOD) and Glutathione peroxidase (GSH-Px) in the brains of AD mice. CONCLUSIONS: On the whole, these findings revealed that HRPI could improve the learning and memory ability and attenuate pathologic impairment in AD mice, and the underlying mechanisms may involve mediating oxidative stress and inflammation, possibly through the regulation of the Keap1/Nrf2 and TLR4/MyD88 signaling pathways. © 2023 Society of Chemical Industry.

Computational Drug Repurposing Based on a Recommendation System and Drug-Drug Functional Pathway Similarity.

Drug repurposing identifies new clinical indications for existing drugs. It can be used to overcome common problems associated with cancers, such as heterogeneity and resistance to established therapies, by rapidly adapting known drugs for new treatment. In this study, we utilized a recommendation system learning model to prioritize candidate cancer drugs. We designed a drug-drug pathway functional similarity by integrating multiple genetic and epigenetic alterations such as gene expression, copy number variation (CNV), and DNA methylation. When compared with other similarities, such as SMILES chemical structures and drug targets based on the protein-protein interaction network, our approach provided better interpretable models capturing drug response mechanisms. Furthermore, our approach can achieve comparable accuracy when evaluated with other learning models based on large public datasets (CCLE and GDSC). A case study about the Erlotinib and OSI-906 (Linsitinib) indicated that they have a synergistic effect to reduce the growth rate of tumors, which is an alternative targeted therapy option for patients. Taken together, our computational method characterized drug response from the viewpoint of a multi-omics pathway and systematically predicted candidate cancer drugs with similar therapeutic effects.

Identifying subpathway signatures for individualized anticancer drug response by integrating multi-omics data.

BACKGROUND: Individualized drug response prediction is vital for achieving personalized treatment of cancer and moving precision medicine forward. Large-scale multi-omics profiles provide unprecedented opportunities for precision cancer therapy. METHODS: In this study, we propose a pipeline to identify subpathway signatures for anticancer drug response of individuals by integrating the comprehensive contributions of multiple genetic and epigenetic (gene expression, copy number variation and DNA methylation) alterations. RESULTS: Totally, 46 subpathway signatures associated with individual responses to different anticancer drugs were identified based on five cancer-drug response datasets. We have validated the reliability of subpathway signatures in two independent datasets. Furthermore, we also demonstrated these multi-omics subpathway signatures could significantly improve the performance of anticancer drug response prediction. In-depth analysis of these 46 subpathway signatures uncovered the essential roles of three omics types and the functional associations underlying different anticancer drug responses. Patient stratification based on subpathway signatures involved in anticancer drug response identified subtypes with different clinical outcomes, implying their potential roles as prognostic biomarkers. In addition, a landscape of subpathways associated with cellular responses to 191 anticancer drugs from CellMiner was provided and the mechanism similarity of drug action was accurately unclosed based on these subpathways. Finally, we constructed a user-friendly web interface-CancerDAP ( http://bio-bigdata.hrbmu.edu.cn/CancerDAP/ ) available to explore 2751 subpathways relevant with 191 anticancer drugs response. CONCLUSIONS: Taken together, our study identified and systematically characterized subpathway signatures for individualized anticancer drug response prediction, which may promote the precise treatment of cancer and the study for molecular mechanisms of drug actions.

Overexpression of ADAMTS5 can regulate the migration and invasion of non-small cell lung cancer.

Non-small cell lung cancer (NSCLC) is the major cause of cancer-related lethality among human cancer patients globally, and the poor prognosis of this cancer is mainly explained by metastasis, so it is essential to find out the molecule mechanisms and a novel therapeutic for NSCLC. A disintegrin and metalloprotease with thrombospondin motif 5 (ADAMTS5) belongs to the protease family. It has been reported to participate in tumor migration and invasion. In this study, we showed that the expression of ADAMTS5 was higher in lung cancer tissues by Western blot. The immunohistochemistry analysis was performed in 140 NSCLC cases, and the result indicated that ADAMTS5 was significantly associated with clinical pathologic variables. The Kaplan-Meier curve showed that the high expression of ADAMTS5 was related to poor prognosis of lung cancer patients. Wound healing assays and transwell migration assays revealed that the high expression of ADAMTS5 promoted the migration and invasion of NSCLC. In a word, our findings suggest that ADAMTS5 can regulate the migration and invasion of NSCLC and it may be a useful target of therapy in NSCLC.

NF45 overexpression is associated with poor prognosis and enhanced cell proliferation of pancreatic ductal adenocarcinoma.

NF45, also referred to as nuclear factor of activated T cells, has been reported to promote the progression of multiple cancer types. However, the expression and physiological significance of NF45 in pancreatic ductal adenocarcinoma (PDAC) remain largely elusive. In this study, we investigated the clinical relevance and potential role of NF45 expression in PDAC development. Western blot analysis revealed that NF45 was remarkably upregulated in PDAC tissues, compared with the adjacent non-tumorous ones. In addition, the expression of NF45 in 122 patients with PDAC was evaluated using immunohistochemistry. In this way, we found that NF45 was abundantly expressed in PDAC tissues, and the expression of NF45 was correlated with tumor size (p = 0.007), histological differentiation (p = 0.033), and TNM stage (p = 0.001). Importantly, patients with low levels of NF45 expression exhibited better postoperative prognosis as compared with those with high NF45 expression. Furthermore, using PDAC cell cultures, we found that interference of NF45 expression using siRNA oligos suppressed PDAC cell proliferation and retarded cell cycle progression. Moreover, depletion of NF45 impaired the levels of cellular cyclin E and proliferating cell nuclear antigen (PCNA). Conversely, overexpression of NF45 facilitated the cell growth and accelerated cell cycle progression. Our results establish NF45 as an important indicator of PDAC prognosis with potential utility as a therapeutic target in this lethal disease.

Measurement of carbon emissions and responsibility sharing for the industrial sector in Zhejiang, China.

Carbon reduction is imperative for achieving carbon peaking and neutrality. Accordingly, it is important to determine which industrial sectors have more responsibility in this matter. Based on data from Zhejiang's input-output tables, this study applies the Input-Output method to measure and compare the carbon emissions of 42 industrial sectors in Zhejiang Province from 2002 to 2017, and then assesses the carbon emission attributes of each industrial sector, and ultimately determines the responsibility for carbon emission reduction from the perspectives of the producers and consumers. The results of the study show that direct carbon emissions and whole-process carbon emissions in Zhejiang increased continuously from 2002 to 2017, with carbon emission intensity first decreasing and then increasing. However, carbon emission intensity was much lower in 2017 than in 2002. Over time, the attributes of carbon emissions by sector changed little. Particularly, high-carbon sectors covered most of the energy supply sectors, low-carbon sectors were mostly tertiary-related, and pseudo-low-carbon sectors were mainly found in the productive services sector. In terms of carbon emission reduction responsibilities, there are large differences in emission reduction responsibilities between sectors, with the electricity and heat sectors bearing the largest responsibilities based on their production, consumption and total carbon emission reductions. The conclusions of this study can provide some data support for the further development of carbon peak and carbon neutral plans.

Dichloroacetate ameliorates apoptosis, EMT and oxidative stress in diabetic cataract via inhibiting the IDO1-dependent p38 MAPK pathway.

As an oral antidiabetic agent, dichloroacetate (DCA) has been proven to improve diabetes and related complications. However, its functional role in diabetic cataract (DC) remains to be elucidated. This study was to define the role of DCA and its underlying molecular mechanism in DC in vitro and in vivo. In this study, it was shown that DCA dose-dependently ameliorated DC formation and development in DM rats. In addition, DCA significantly increased cell viability, reduced apoptosis, and inhibited EMT and oxidative stress of high glucose (HG)-treated SRA-01/04 cells in a concentration-dependent manner. Besides, it was revealed that Indoleamine 2,3-dioxygenase 1 (IDO1) expression was upregulated in lenses of DM rats and HG-treated SRA-01/04 cells, which was reversed by DCA. In addition, DCA abrogated the activation of the p38 MAPK signaling in the lenses of DM rats and HG-treated SRA-01/04 cells. Further experiments showed that IDO1 upregulation activated the p38 MAPK signaling in HG-challenged SRA-01/04 cells. Moreover, IDO1 overexpression partially reversed DCA-mediated inactivation of p38 MAPK signaling and suppression of HG-induced damage to SRA-01/04 cells. To sum up, our findings showed that DCA prevented DC-related apoptosis, EMT, and oxidative stress via inactivating IDO1-dependent p38 MAPK signaling.

Identification of Diagnostic Biomarkers in Systemic Lupus Erythematosus Based on Bioinformatics Analysis and Machine Learning.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that affects several organs and causes variable clinical symptoms. Exploring new insights on genetic factors may help reveal SLE etiology and improve the survival of SLE patients. The current study is designed to identify key genes involved in SLE and develop potential diagnostic biomarkers for SLE in clinical practice. Expression data of all genes of SLE and control samples in GSE65391 and GSE72509 datasets were downloaded from the Gene Expression Omnibus (GEO) database. A total of 11 accurate differentially expressed genes (DEGs) were identified by the "limma" and "RobustRankAggreg" R package. All these genes were functionally associated with several immune-related biological processes and a single KEGG (Kyoto Encyclopedia of Genes and Genome) pathway of necroptosis. The PPI analysis showed that IFI44, IFI44L, EIF2AK2, IFIT3, IFITM3, ZBP1, TRIM22, PRIC285, XAF1, and PARP9 could interact with each other. In addition, the expression patterns of these DEGs were found to be consistent in GSE39088. Moreover, Receiver operating characteristic (ROC) curves analysis indicated that all these DEGs could serve as potential diagnostic biomarkers according to the area under the ROC curve (AUC) values. Furthermore, we constructed the transcription factor (TF)-diagnostic biomarker-microRNA (miRNA) network composed of 278 nodes and 405 edges, and a drug-diagnostic biomarker network consisting of 218 nodes and 459 edges. To investigate the relationship between diagnostic biomarkers and the immune system, we evaluated the immune infiltration landscape of SLE and control samples from GSE6539. Finally, using a variety of machine learning methods, IFI44 was determined to be the optimal diagnostic biomarker of SLE and then verified by quantitative real-time PCR (qRT-PCR) in an independent cohort. Our findings may benefit the diagnosis of patients with SLE and guide in developing novel targeted therapy in treating SLE patients.

CRIT: Identifying RNA-binding protein regulator in circRNA life cycle via non-negative matrix factorization.

Circular RNAs (circRNAs) are endogenous non-coding RNAs that regulate gene expression and participate in carcinogenesis. However, the RNA-binding proteins (RBPs) involved in circRNAs biogenesis and modulation remain largely unclear. We developed the circRNA regulator identification tool (CRIT), a non-negative matrix-factorization-based pipeline to identify regulating RBPs in cancers. CRIT uncovered 73 novel regulators across thousands of samples by effectively leveraging genomics data and functional annotations. We demonstrated that known RBPs involved in circRNA control are significantly enriched in these predictions. Analysis of circRNA-RBP interactions using two large cross-linking immunoprecipitation (CLIP) databases, we validated the consistency between CRIT prediction and the CLIP experiments. Furthermore, newly discovered RBPs are functionally connected with authentic circRNA regulators by various biological associations, such as physical interaction, similar binding motifs, common transcription factor modulation, and co-expression. When analyzing RNA sequencing (RNA-seq) datasets after short hairpin RNA (shRNA)/small interfering RNA (siRNA) knockdown, we found several novel RBPs that can affect global circRNA expression, which strengthens their role in the circRNA life cycle. The above evidence provided independent confirmation that CRIT is a useful tool to capture RBPs in circRNA processing. Finally, we show that authentic regulators are more likely the core splicing proteins and peripheral factors and usually harbor more alterations in the vast majority of cancers.

Protective effect of flavonoids extract of Hippophae rhamnoides L. on alcoholic fatty liver disease through regulating intestinal flora and inhibiting TAK1/p38MAPK/p65NF-κB pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: The therapeutic properties of Hippophae rhamnoides L. were already known in ancient Greece as well as in Tibetan and Mongolian medicine. Modern studies have indicated that Hippophae rhamnoides L. fermentation liquid protected against alcoholic fatty liver disease (AFLD). However, the underlying mechanism of Hippophae rhamnoides L. flavonoids extract (HLF) treating AFLD remains elusive. AIM OF THE STUDY: This study aimed to investigate the hepatoprotective effect of HLF in mice with AFLD and the interaction between AFLD and gut microbiota. MATERIALS AND METHODS: Chemical constituents of HLF were analyzed by Liquid Chromatography-Ion Trap-ESI-Mass Spectrometry. The Hepatoprotective effect of HLF was evaluated in mice with AFLD induced by alcohol (six groups, n = 10) daily at doses of 0.1, 0.2, and 0.4 g/kg for 30 consecutive days. At the end of experiment, mice were sacrificed and the liver, serum and feces were harvested for analysis. The liver histological changes were observed by H&E staining and oil red O staining. Moreover, the alterations of fecal microflora were detected by 16S rRNA gene sequencing. The inflammatory related genes were determined by qRT-PCR and western blotting respectively. RESULTS: The results showed that the oral administration of HLF remarkably alleviated hepatic lipid accumulation by decreasing the levels of ALT, AST, TG and TC. The levels of TNF-α, TGF-ß, and IL-6 were also reduced after treatment with HLF. Meanwhile, the protein and mRNA expression of NF-kB p65, MAPK p38 and TAK-1 in the liver of mice with AFLD were all reduced by HLF compared with model group. Furthermore, the 16S rRNA gene sequencing analysis demonstrated that HLF treatment can help restore the imbalance of intestinal microbial ecosystem and reverse the changes in Fimicutes/Bacterodietes, Clostridiales, Lachnospiraceae, S24-7, and Prevotella in mice with AFLD. CONCLUSION: HLF can effectively ameliorate liver injury in mice with AFLD, and regulate the composition of gut microbiota. Its regulatory mechanism may be related to TAK1/p38MAPK/p65NF-κB pathway. This study may provide novel insights into the mechanism of HLF on AFLD and a basis for promising clinical usage.

Seabuckthorn polysaccharide combined with astragalus polysaccharide ameliorate alcoholic fatty liver by regulating intestinal flora.

Background: At present, the incidence of alcoholic fatty liver disease (AFLD) is increasing year by year, and numerous studies have confirmed that liver diseases are closely related to intestinal flora. Seabuckthorn and Astragalus membranaceus, as traditional Chinese medicine (TCM) with the homology of medicine and food, have good liver protection, and their polysaccharides can regulate the intestinal flora. Here, we studied the effects of HRP, APS and the combination of the two polysaccharides on the intestinal flora of AFLD mice, which provided scientific basis for the treatment of AFLD with the two polysaccharides. Materials and methods: Thirty Kunming (KM) mice were randomly divided into the control group (Con), the model group (Mod), the HRP treatment group (HRP), the APS treatment group (APS), and HRP+APS treatment group (HRP+APS), with six mice in each group. The AFLD model was constructed by continuous intragastric administration of 42% vol Niulanshan ethanol solution for 28 days, and the mice in each polysaccharide group were given corresponding drugs. The levels of AST, ALT, TC and TG in serum of mice were measured. 16S rRNA amplicon sequencing technique was used to determine the diversity and richness of intestinal flora, and the relative abundance of intestinal flora at phylum level and genus level of the mice in each group. Results: HRP, APS and HRP+APS could reduce the serum levels of AST, ALT, TC and TG in mice. In addition, HRP, APS and HRP + APS restored the diversity, relative abundance and community structure of intestinal mucosa bacteria in AFLD mice to a certain extent. Specifically, HRP, APS and HRP+APS remarkably decreased the ratio of Firmicutes to Bacteroidetes, and ultimately increased the abundance of beneficial bacteria and reduced the abundance of pathogenic bacteria. Conclusion: HRP, APS, and HRP+APS can improve the intestinal microecology of AFLD model mice, alleviate liver injury, and maintain normal intestinal function in different degrees.

Characterizing the tumor RBP-ncRNA circuits by integrating transcriptomics, interactomics and clinical data.

The interactions among non-coding RNA (ncRNA) and RNA binding protein (RBP) are increasingly recognized as one of basic mechanisms in gene regulation, and play a crucial role in cancer progressions. However, the current understanding of this regulation network, especially its dynamic spectrum according to the differentially expressed nodes (i.e. ncRNAs and RBP) is limited. Utilizing transcriptomics and interactomics resources, dysregulated RBP-ncRNA circuits (RNCs) are systematically dissected across 14 tumor types. We found these aberrant RNCs are robust and enriched with cancer-associated ncRNAs, RBPs and drug targets. Notably, the nodes in altered RNCs can jointly predict the clinical outcome while the individual node can't, underscoring RNCs can serve as prognostic biomarkers. We identified 30 pan-cancer RNCs dysregulated at least in six tumor types. Pan-cancer RNC analysis can reveal novel mechanism of action (MOA) and repurpose for existing drugs. Importantly, our experiments elucidated the novel role of hsa-miR-224-5p, a member of the pan-cancer RNC hsa-miR-224-5p_MAGI2-AS3_MBNL2, in EMT program. Our analysis highlights the potential utilities of RNCs in elucidating ncRNA function in cancer, associating with clinical outcomes and discovering novel drug targets or MOA.

The prognostic value of prognostic nutritional index (PNI) and neutrophil to lymphocyte ratio (NLR) for advanced non-small cell lung cancer treated with platinum-based chemotherapeutics.

BACKGROUND: The present study aimed to investigate the relationship between prognostic nutritional index (PNI) and peripheral blood neutrophil to lymphocyte ratio (NLR), and the prognosis of patients with advanced non-small cell lung cancer (NSCLC) treated with platinum-based therapeutics. METHODS: The data of 99 advanced NSCLC patients treated with platinum chemotherapeutics between January 2011 and June 2019 were retrospectively analyzed. The association between PNI and NLR and the clinicopathological characteristics of the patients was examined. The patients were randomized into high or low groups according to PNI and NLR. The predictive value of PNI and NLR for overall survival (OS) was evaluated by receiver operating characteristic (ROC) curve analysis. Univariate and multivariate Cox proportional hazards regression analyses were performed to investigate the prognostic factors of advanced NSCLC patients treated with platinum-based chemotherapeutics. The association between PNI and NLR and progression-free survival (PFS) or OS was determined using the Kaplan-Meier method and compared between groups using the log-rank test. RESULTS: The ROC curve analysis determined the optimal cut-off values of PNI and NLR for predicting OS to be 52.525 and 3.525, respectively. Univariate analysis indicated that low Karnofsky performance scale (KPS) score (P=0.005), poor tumor differentiation (P=0.022), brain metastasis (P<0.001), and low PNI (P=0.001) were independent risk factors for PFS in patients with advanced NSCLC; however, there was no significant correlation observed between NLR (P=0.082) and PFS in patients with advanced NSCLC. Low KPS score (P=0.003), poor tumor differentiation (P=0.001), brain metastasis (P<0.001), low PNI (P<0.001), and high NLR (P=0.046) were significantly associated with shorter OS. Furthermore, Cox multivariate analysis revealed that brain metastasis (P=0.005) and low PNI (P=0.008) were significant independent prognostic factors for PFS, while brain metastasis (P=0.003) and low PNI (P=0.028) were also found to be significant independent risk factors for poor OS. CONCLUSIONS: PNI is a reliable, simple, easily available, and inexpensive biomarker for predicting the prognosis of advanced NSCLC patients treated with platinum-based chemotherapeutics in routine clinical practice. Furthermore, PNI is superior to NLR in as a prognostic indicator for advanced NSCLC patients treated with platinum-based chemotherapeutics.

High VRK1 expression contributes to cell proliferation and survival in hepatocellular carcinoma.

VRK1 is a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases, which is known to play multiple roles in cellular proliferation, cell cycle regulation and carcinogenesis. However, the expression and physiological significance of VRK1 in hepatocellular carcinoma (HCC) remain unclear. In this study, we aimed to investigate the potential role of VRK1 in the development and progression of HCC. Western blot and immunohistochemical analysis revealed that VRK1 was highly expressed in HCC tissues and cell lines, compared with adjacent nontumorous tissues and LO2 normal hepatocytes. Meanwhile, clinicopathological analysis showed that VRK1 was significantly associated with AJCC stage, Ki-67 and a poor prognosis in HCC specimens. Univariate and multivariate analysis showed that VRK1 could serve as an independent prognostic indicator of HCC patients' survival. Furthermore, we found that VRK1 was lowly expressed in serum-starved Huh7 cells, and was progressively increased after serum-refeeding. Finally, flow cytometry, CCK-8 and colony formation assay indicated that the depletion of VRK1 could retard cell cycle progression and reduce cells proliferation in HCC cells. On the basis of these findings, we conclude that VRK1 may be a candidate prognostic biomarker as well as a potential therapeutical target of HCC.

Overexpression of HOXC8 is Associated With Poor Prognosis in Epithelial Ovarian Cancer.

Homeobox C8 (HOXC8) is a transcription factor that has been reported as a potential driver oncogene in several tumors and involved in the regulation of many cancer-related proteins. In this study, we investigated the expression and role of HOXC8 in ovarian cancer. Western blot and immunohistochemistry analyses were performed to detect the expression of HOXC8. Kaplan-Meier curve showed that high expression of HOXC8 was related to poor prognosis of patients with epithelial ovarian cancer (EOC). Starvation and refeeding assay were used to assess cell cycle, suggesting that HOXC8 played a critical role in EOC cell proliferation. HOXC8 depletion by small interfering RNA inhibited cell proliferation, migration, and induced apoptosis in EOC cells. Moreover, HOXC8 knockdown increased the expression of ZAC1. Owing to the overexpression of HOXC8, our findings implied that HOXC8 is involved in the progression of EOC and could be a potential therapeutical approach of EOC.

PFTK1 Promotes Gastric Cancer Progression by Regulating Proliferation, Migration and Invasion.

PFTK1, also known as PFTAIRE1, CDK14, is a novel member of Cdc2-related serine/threonine protein kinases. Recent studies show that PFTK1 is highly expressed in several malignant tumors such as hepatocellular carcinoma, esophageal cancer, breast cancer, and involved in regulation of cell cycle, tumors proliferation, migration, and invasion that further influence the prognosis of tumors. However, the expression and physiological significance of PFTK1 in gastric cancer remain unclear. In this study, we analyzed the expression and clinical significance of PFTK1 by Western blot in 8 paired fresh gastric cancer tissues, nontumorous gastric mucosal tissues and immunohistochemistry on 161 paraffinembedded slices. High PFTK1 expression was correlated with the tumor grade, lymph node invasion as well as Ki-67. Through Cell Counting Kit (CCK)-8 assay, flow cytometry, colony formation, wound healing and transwell assays, the vitro studies demonstrated that PFTK1 overexpression promoted proliferation, migration and invasion of gastric cancer cells, while PFTK1 knockdown led to the opposite results. Our findings for the first time supported that PFTK1 might play an important role in the regulation of gastric cancer proliferation, migration and would provide a novel promising therapeutic strategy against human gastric cancer.