Structural insights into the ubiquitylation strategy of the oligomeric CRL2FEM1B E3 ubiquitin ligase.

Cullin-RING E3 ubiquitin ligase (CRL) family members play critical roles in numerous biological processes and diseases including cancer and Alzheimer's disease. Oligomerization of CRLs has been reported to be crucial for the regulation of their activities. However, the structural basis for its regulation and mechanism of its oligomerization are not fully known. Here, we present cryo-EM structures of oligomeric CRL2FEM1B in its unneddylated state, neddylated state in complex with BEX2 as well as neddylated state in complex with FNIP1/FLCN. These structures reveal that asymmetric dimerization of N8-CRL2FEM1B is critical for the ubiquitylation of BEX2 while FNIP1/FLCN is ubiquitylated by monomeric CRL2FEM1B. Our data present an example of the asymmetric homo-dimerization of CRL. Taken together, this study sheds light on the ubiquitylation strategy of oligomeric CRL2FEM1B according to substrates with different scales.

Systematic review and meta-analysis of probiotics in the treatment of allergic rhinitis.

BACKGROUND: The purpose of this meta-analysis is to systematically evaluate the efficacy of probiotics on allergic rhinitis (AR). METHODS: Collecting randomized controlled trials (RCTs) with probiotics as intervention measures for AR, two researchers independently screened the literature, extracted the data and evaluated the methodological quality of the included studies, and used RevMan 5.3 software for meta-analysis to observe the effects of probiotics on Rhinitis Quality of Life (RQLQ) scores, Rhinitis Total Symptom Scores (RTSS), blood eosinophil count, total and antigen-specific serum immunoglobulin E (IgE) levels by using the fixed- or the random-effects model to calculate the pooled risk for significant heterogeneity. RESULTS: A total of 2708 patients were included in 30 RCTs. Meta-analysis results showed that the RQLQ global scores (mean difference [MD] = -9.43; P < 0.00001), RQLQ nasal scores (MD = -1.52; P = 0.03), and RTSS nasal scores (MD = -1.96; P = 0.02) significantly improved in the probiotic group when compared with those in the placebo group. There was no significant difference in blood eosinophil count (MD = -0.09; P=0.82), RQLQ eye scores (MD = -1.45; P = 0.07), RTSS global scores (MD = -2.24; P = 0.26), RTSS eye scores (MD = -0.39; P = 0.31), total and antigen-specific serum IgE levels (MD = -0.04; P = 0.7 and MD = -0.08; P = 0.81) between the probiotic and the placebo group. CONCLUSION: Compared with the placebo group, the quality of life and symptoms of patients with AR significantly improved in the probiotic group, thus providing a new potential method for the application of probiotics in AR. However, because of the limited evidence for the current study outcomes, the heterogeneity of research, and the differences in research results, more high-quality studies are needed to in the future.

Monocarboxylate transporter 1 promotes proliferation and invasion of renal cancer cells by mediating acetate transport.

One hallmark of renal cell carcinoma (RCC) is metabolic reprogramming, which involves elevation of glycolysis and upregulation of lipid metabolism. However, the mechanism of metabolic reprogramming is incompletely understood. Monocarboxylate transporter 1 (MCT1) promotes transport for lactate and pyruvate, which are crucial for cell metabolism. The aim of present study was to investigate the function of MCT1 on RCC development and its mechanism on metabolic reprogramming. The results showed that MCT1 messenger RNA and protein levels significantly increased in cancer tissues of ccRCC compared to normal tissue. MCT1 was further found to mainly located in the cell membrane of RCC. The knockdown of MCT1 by RNAi significantly inhibited proliferation and migration of 786-O and ACHN cells. MCT1 also induced the expressions of proliferation marker Ki-67 and invasion marker SNAI1. Moreover, we also showed that acetate treatment could upregulate the expression of MCT1, but not other MCT isoforms. On the other hand, MCT1 was involved in acetate transport and intracellular histone acetylation. In summary, this study revealed that MCT1 is abnormally high in ccRCC and promotes cancer development. The regulatory effect of MCT1 on cell proliferation and invasion maybe mediated by acetate transport.

LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC.

Various studies demonstrate that long noncoding RNAs (lncRNAs) act as oncogenes or tumor suppressors in cancer. However, the function of lncRNAs in bladder cancer still remains largely unknown. In this study, we identified an lncRNA, gastric cancer-associated lncRNA1 (GClnc1), which was in high abundance in bladder cancer tissues and its expression was related to poor survival rates in patients with bladder cancer. In vitro and in vivo assays showed that GClnc1 significantly promoted cell proliferation, metastasis, and invasiveness in bladder cancer. Mechanistically, we first found that GClnc1 bound to LIN28B and promoted the expression of myelocytomatosis proto-oncogene (MYC) through the LIN28B/let-7a/MYC pathway. In short, GClnc1 is clinically, functionally, and mechanistically oncogenic in bladder cancer. GClnc1 may be a potential target for treating patients with bladder cancer.-Zhuang, C., Ma, Q., Zhuang, C., Ye, J., Zhang, F., Gui, Y. LncRNA GClnc1 promotes proliferation and invasion of bladder cancer through activation of MYC.

N6-methyladenosine demethylase FTO suppresses clear cell renal cell carcinoma through a novel FTO-PGC-1α signalling axis.

The abundant and reversible N6-methyladenosine (m6A) RNA modification and its modulators have important roles in regulating various gene expression and biological processes. Here, we demonstrate that fat mass and obesity associated (FTO), as an m6A demethylase, plays a critical anti-tumorigenic role in clear cell renal cell carcinoma (ccRCC). FTO is suppressed in ccRCC tissue. The low expression of FTO in human ccRCC correlates with increased tumour severity and poor patient survival. The Von Hippel-Lindau-deficient cells expressing FTO restores mitochondrial activity, induces oxidative stress and ROS production and shows impaired tumour growth, through increasing expression of PGC-1α by reducing m6A levels in its mRNA transcripts. Our work demonstrates the functional importance of the m6A methylation and its modulator, and uncovers a critical FTO-PGC-1α axis for developing effective therapeutic strategies in the treatment of ccRCC.

TBC1D20 deficiency induces Sertoli cell apoptosis by triggering irreversible endoplasmic reticulum stress in mice.

Male 'blind sterile' mice with the causative TBC1 domain family member 20 (TBC1D20) deficiency are infertile with excessive germ cell apoptosis and spermatogenesis arrest at the spermatid stage. Sertoli cells are characterised as 'nurse cells' essential for normal spermatogenesis, but the role and corresponding molecular mechanisms of TBC1D20 deficiency in Sertoli cells of mice are not clear to date. In the present study, the histopathology of the testis and Sertoli cell proliferation and apoptosis were determined, and the corresponding molecular mechanisms were investigated by western blotting. Our data showed that TBC1D20 exhibits a testis-abundant expression pattern, and its expression level is positively associated with spermatogenesis. TBC1D20 is assembled in the Golgi and endoplasmic reticulum and is widely expressed by various germ cell subtypes and Sertoli cells. TBC1D20 deficiency in Sertoli cells led to an excessive apoptosis ratio and G1/S arrest. The increased apoptosis of TBC1D20-deficient Sertoli cells resulted from caspase-12 activation. TBC1D20-deficient Sertoli cells had an abnormal Golgi-endoplasmic reticulum structure, which led to endoplasmic reticulum stress, resulting in cell cycle arrest and excessive apoptosis. It suggested that TBC1D20 deficiency triggers irreversible endoplasmic reticulum stress resulting in G1/S arrest and excessive apoptosis in TBC1D20-deficient Sertoli cells, and TBC1D20 deficiency in Sertoli cells may also contribute to the infertility phenotype in 'blind sterile' male mice.

Relationship Between SLC22A1 and SLC22A4 Gene Polymorphisms and Risk of Type 2 Diabetes in Chinese Han Population.

BACKGROUND: This study was to investigate the relationship between SLC22A1 and SLC22A4 gene polymorphisms and genetic susceptibility to type 2 diabetes in Chinese Han population. METHODS: The research group comprised 110 Chinese Han patients with type 2 diabetes, and the control group included 110 healthy volunteers. The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs2073838 and rs272893 loci were detected in the two groups. RESULTS: Statistically significant differences were identified in the genotype distributions of SLC22A1 gene rs628031 and rs2282143 loci between the two groups (p < 0.05). The A allele frequency of SLC22A1 gene rs628031 locus and the T allele frequency of rs2282143 locus were higher in the research group than in the control group (p < 0.05). The genotype distributions of rs272893 locus showed a significant difference between the two groups (p < 0.05), but not SLC22A4 gene rs2073838 locus (p > 0.05). CONCLUSIONS: The polymorphisms of SLC22A1 gene rs628031 and rs2282143 loci and SLC22A4 gene rs272893 locus of patients with type 2 diabetes indicated a significant difference between the two groups, suggesting that these genetic locus mutations increase the risk of type 2 diabetes in Chinese Han patients.

Investigation of the interactions between methylene blue and intramolecular G-quadruplexes: an explicit distinction in electrochemical behavior.

G-quadruplex sequences exist in eukaryotic organisms and prokaryotes, and the investigation of the interactions between G-quadruplexes and small molecule ligands is important for gene therapy, biosensor fabrication, fluorescence imaging and so on. Here, we investigated the behaviour of methylene blue (MB), an electroactive molecule, in the presence of different intramolecular G-quadruplexes by an electrochemical method using a miniaturized electrochemical device based on its intrinsic electrochemical properties. Although the effects of MB on different intramolecular G-quadruplex structures are not obvious by circular dichroism spectroscopy, distinct differences in the binding affinities of MB with different intramolecular G-quadruplexes were quickly and easily observed by an electrochemical technique. At the same time, for the human telomerase G-rich sequence (HT), the diffusion current of MB changed sensitively under different ionic conditions due to the formation of different conformations of HT, which indicated that our electrochemical method has the potential to study the influence of metal ions on the conformations of the G-quadruplexes with simplicity, rapid response and low cost. From all these, a new stacking mechanism and rule were obtained, which were also validated by docking studies and isothermal titration calorimetry (ITC).

Curative effect of 1.88-mg and 3.75-mg gonadotrophin-releasing hormone agonist on stage III-IV endometriosis: Randomized controlled study.

AIM: To compare the therapeutic effect of 1.88-mg and 3.75-mg gonadotrophin-releasing hormone agonist (GnRHa) in the treatment of stage III-IV endometriosis after laparoscopic surgery. METHODS: Fifty patients with stage III-IV endometriosis diagnosed on laparoscopy were randomized into two groups according to GnRHa dose. Sex hormone level, symptoms of estrogen deficiency and lumbar vertebrae bone density were compared and analyzed between the two groups. RESULTS: Bone density was decreased in both groups at 20 weeks after treatment, and the degree of bone density loss in the full-dose group (5.6%) was higher than in the half-dose group (1.2%; P < 0.05). Surgery combined with the 3.75-mg GnRHa or with the 1.88-mg GnRHa relieved the degree of dysmenorrhea, although one case of light dysmenorrhea occurred in each group, but there was no significant difference (P > 0.05) after resumption of menstruation. Both groups had symptoms of perimenopause at 8 weeks after treatment (P > 0.05), but change in Kupperman score with time differed between the groups. At 16, 20 weeks after treatment, the symptoms of perimenopause in the half-dose group were improved, and Kupperman score was lower than at 8 weeks after treatment. In the full-dose group, however, Kupperman score was higher than at 8 weeks after treatment and higher than in the half-dose group (P < 0.05). After treatment, follicle-stimulating hormone and luteinizing hormone both decreased in both groups (P < 0.05), but there was no difference between the two groups (P > 0.05). Estradiol (E2) in the full-dose group was significantly lower than in the half-dose group (P < 0.05). CONCLUSION: The 1.88-mg GnRHa treatment can be used in III-IV endometriosis patients after laparoscopic surgery, to reduce perimenopausal symptoms, significantly improve bone loss, and achieve a good clinical effect.

Portable, Easy-to-Operate, and Antifouling Microcapsule Array Chips Fabricated by 3D Ice Printing for Visual Target Detection.

Herein, we proposed a portable, easy-to-operate, and antifouling microcapsule array chip for target detection. This prepackaged chip was fabricated by innovative and cost-effective 3D ice printing integrating with photopolymerization sealing which could eliminate complicated preparation of wet chemistry and effectively resist outside contaminants. Only a small volume of sample (2 µL for each microcapsule) was consumed to fulfill the assay. All the reagents required for the analysis were stored in ice form within the microcapsule before use, which guaranteed the long-term stability of microcapsule array chips. Nitrite and glucose were chosen as models for proof of concept to achieve an instant quantitative detection by naked eyes without the need of external sophisticated instruments. The simplicity, low cost, and small sample consumption endowed ice-printing microcapsule array chips with potential commercial value in the fields of on-site environmental monitoring, medical diagnostics, and rapid high-throughput point-of-care quantitative assay.

A smart tailor-made G-clip reporter for sensitive detection of G-triplet-containing sequences.

Taking advantage of the intrinsic characteristics of G-triplet-containing sequences, a pioneering tailor-made clip-like reporter containing three-fourths of a G-quadruplex is established. The reporter can clip the G triplet in the target sequence through a recognition process to form a complete G-quadruplex structure.

Methylene blue as a G-quadruplex binding probe for label-free homogeneous electrochemical biosensing.

Herein, G-quadruplex sequence was found to significantly decrease the diffusion current of methylene blue (MB) in homogeneous solution for the first time. Electrochemical methods combined with circular dichroism spectroscopy and UV-vis spectroscopy were utilized to systematically explore the interaction between MB and an artificial G-quadruplex sequence, EAD2. The interaction of MB and EAD2 (the binding constant, K ≈ 1.3 × 10(6) M(-1)) was stronger than that of MB and double-stranded DNA (dsDNA) (K ≈ 2.2 × 10(5) M(-1)), and the binding stoichiometry (n) of EAD2/MB complex was calculated to be 1.0 according to the electrochemical titration curve combined with Scatchard analysis. MB was proved to stabilize the G-quadruplex structure of EAD2 and showed a competitive binding to G-quadruplex in the presence of hemin. EAD2 might mainly interact with MB, a positive ligand of G-quadruplex, through the end-stacking with π-system of the guanine quartet, which was quite different from the binding mechanism of dsDNA with MB by intercalation. A novel signal read-out mode based on the strong affinity between G-quadruplex and MB coupling with aptamer/G-quadruplex hairpin structure was successfully implemented in cocaine detection with high specificity. G-quadruplex/MB complex will function as a promising electrochemical indicator for constructing homogeneous label-free electrochemical biosensors, especially in the field of simple, rapid, and noninvasive biochemical assays.

A G-quadruplex based platform for label-free monitoring of DNA reaction kinetics.

Research on the kinetic characteristics and mechanisms of DNA reactions is crucial for bioengineering and biosensing. A G-quadruplex, which can form a peroxidase-mimicking DNAzyme with hemin, was for the first time used to establish a versatile platform for kinetic investigations on DNA reactions. G-quadruplex sequence EAD2 was incorporated into the corresponding nucleic acid reaction as product. The kinetic curves can be obtained rapidly and simply via the quantification of created DNAzyme. In this paper, the kinetics of isothermal linear strand displacement amplification reactions with different DNA lengths and isothermal exponential amplification reactions were successfully elucidated via the G-quadruplex based monitoring platform. As a safe and accessible alternative to the traditional methods, this robust, label-free, time-saving and high-throughput platform shows great potential for the exploration of more novel DNA reactions or circuits in an ingenious manner.

Novel homogeneous label-free electrochemical aptasensor based on functional DNA hairpin for target detection.

We first developed a label-free and immobilization-free homogeneous electrochemical aptasensor, which combined a smart functional DNA hairpin and a designed miniaturized electrochemical device. Cocaine was chosen as a model target. The anticocaine aptamer and peroxidase-mimicking DNAzyme were integrated into one single-stranded DNA hairpin. Both aptamer and G-quadruplex were elaborately blocked by the stem region. The conformation switching induced by the affinity interaction between aptamer and cocaine released G-quadruplex part and turned on DNAzyme activity. The designed electrochemical device, constructed by a disposable micropipet tip and a reproducible carbon fiber ultramicroelectrode, was applied to the detection of homogeneous DNAzyme catalytic activity at the microliter level. The aptasensor realized the quantification of cocaine ranging from 1 to 500 µM with high specificity. The clever combination of the functional DNA hairpin and the novel device achieved an absolutely label-free electrochemical aptasensor, which showed excellent performance like low cost, easy operation, rapid detection, and high repeatability.

Identification of the VIL2 enhancer in human embryonic kidney cells.

We previously demonstrated that the VIL2 -87/+134 region exhibited promoter activity in some human cells, and a region further upstream of this promoter might contain an enhancer. However, the properties and location of this VIL2 enhancer remain unclear. In this study, we cloned the VIL2 -1541/-706 segment and investigated its transcriptional regulatory properties via luciferase assays in transiently transfected HEK-293 cells (human embryonic kidney cells). The VIL2 -1541/-706 was found to exhibit promoter activity. Furthermore, when this segment was located upstream of the VIL2 or SV40 (simian virus 40) promoters in the forward orientation, the expression levels of luciferase were dramatically enhanced. However, this transcriptional enhancement disappeared when this segment was located upstream of the promoter in the reverse orientation or downstream of the reporter gene in the forward or reverse orientation. In deletion experiments, we found several potential regulatory regions within the VIL2 -1541/-706. When these regions were separately located upstream of the VIL2 or SV40 promoters, only the -1297/-1186 considerably enhanced the activity of these promoters. Although the other regulatory regions exhibited significant transcriptional regulation in deletion experiments, they weakly enhanced VIL2 promoter activity and/or did not regulate SV40 promoter activity. These results suggest that the DNA sequence upstream of the VIL2 promoter functions as an enhancer in a position- and orientation-dependent manner, and the VIL2 -1297/-1186, which acts as a key enhancer, probably regulates VIL2 transcription in combination with other potential regulatory regions located upstream of the VIL2 promoter.

Application of Visual Gene Clip-Based Tailored Therapy for the Eradication of Helicobacter pylori.

BACKGROUND: Helicobacter pylori eradication with therapies employing a proton pump inhibitor (PPI) and antimicrobial agents is mainly achieved via bacterial susceptibility to antimicrobial agents and the magnitude of acid secretion inhibition. However, annual eradication rates have greatly declined in Mainland China, and therefore, tailored H. pylori eradication regimens that inhibit acid secretion and employ optimal antimicrobial agents determined based on gene clip testing may improve eradication rates. This study was aimed at evaluating the efficacy of tailored H. pylori eradication therapy guided by visual gene clip testing for antibiotic resistance and PPI metabolism genotypes. METHODS: This prospective study included 244 patients (141 men and 103 women aged 20-79 years) receiving initial treatment for H. pylori infection. Visual gene clip testing using gastric mucosal specimens was performed to detect antibiotic resistance to clarithromycin conferred by the A2142G and A2143G point mutations of the H. pylori 23S rRNA gene and to levofloxacin conferred by the Asn87 and Asp91 point mutations of the H. pylori gyrA gene. Patients received a 14-day bismuth quadruple therapy regimen guided by testing for antibiotic resistance and CYP2C19 polymorphisms, and primary H. pylori eradication was assessed at least 4 weeks after therapy. RESULTS: H. pylori strains were successfully isolated from the gastric mucosa tissues of 244 patients. Antibiotic resistant isolates were identified in 63 patients, with clarithromycin resistance observed in 50 patients, levofloxacin resistance in 7 patients, and dual resistance in 6 patients. The PPI metabolic genotype of CYP2C19 was detected in 242 of 244 cases, and 97 cases were categorized as extensive metabolizers, 141 as intermediate metabolizers, and 4 as poor metabolizers. Among the 242 patients who received tailored therapy, the H. pylori eradication rate was 90.9% (95% confidence interval 87.3%~94.6%) in the intention-to-treat analysis and 96.9% (95% confidence interval 94.7%~99.2%) in the per protocol analysis. CONCLUSIONS: Tailored therapy for H. pylori infection guided by determination of antibiotic resistance and CYP2C19 polymorphism using visual gene chip technology may provide high clinical effectiveness as initial H. pylori eradication therapy.

miR-638 acts as an oncogene and predicts poor prognosis in renal cell carcinoma.

OBJECTIVE: The aim of this study was to investigate the function and prognostic value of miR-638 in renal cell carcinoma (RCC). METHODS: Expression of miR-638 in RCC tissues and corresponding noncancerous tissues were examined by reverse transcription quantitative polymerase chain reaction (RT-qPCR). To explore the effects of miR-638 on cell migration, invasion, viability, and apoptosis of RCC cells, wound scratch, transwell, MTT, CCK-8, and flow cytometry assays were performed. Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between miR-638 expression and prognosis of RCC patients. Potential target genes of miR-638 were predicted and validated via multiple bioinformatics analyses. RESULTS: miR-638 was upregulated in RCC tissues when compared with corresponding noncancerous tissues (P < 0.05). Upregulation of miR-638 expression by transfection with a synthetic miR-638 mimic promoted cell migration, invasion, and viability and suppressed cell apoptosis. Moreover, Kaplan-Meier analysis revealed that upregulation of miR-638 associated with shorter overall survival (OS; P = 0.001). Cox univariate and multivariate regression analysis suggested that miR-638 expression is an independent predictive factor for the prognosis of RCC patients (P = 0.004). KCNQ1, DNAJC6, and PNP were identified as potential target genes of miR-638. CONCLUSIONS: The results of this study demonstrated that miR-638 functions as an oncogene in RCC and has the potential to be a prognostic biomarker for RCC.

Acetate promotes SNAI1 expression by ACSS2-mediated histone acetylation under glucose limitation in renal cell carcinoma cell.

Metastasis is the main cause of cancer-associated deaths, yet this complex process is still not well understood. Many studies have shown that acetate is involved in cancer metastasis, but the molecular mechanisms remain to be elucidated. In the present study, we first measured the effect of acetate on zinc finger transcriptional repressor SNAI1 and acetyl-CoA synthetase 2 (ACSS2) under glucose limitation in renal cell carcinoma cell lines, 786-O and ACHN. Then, RNA interference and overexpression of ACSS2 were used to detect the role of acetate on SNAI1 expression and cell migration. Finally, chromatin immunoprecipitation assay (ChIP) was used to investigate the regulatory mechanism of acetate on SNAI1 expression. The results showed that acetate increased the expressions of SNAI1 and ACSS2 under glucose limitation. ACSS2 knockdown significantly decreased acetate-induced SNAI1 expression and cell migration, whereas overexpression of ACSS2 increased SNAI1 level and histone H3K27 acetylation (H3K27ac). ChIP results revealed that acetate increased H3K27ac levels in regulatory region of SNAI1, but did not increase ACSS2-binding ability. Our study identified a novel inducer, acetate, which can promote SNAI1 expression by ACSS2-mediated histone acetylation in partly. This finding has important implication in treatment of metastatic cancers.

LncRNA NRON promotes the proliferation, metastasis and EMT process in bladder cancer.

Background: Bladder cancer (BC) is one of the most common malignancies world-wide with high morbidity and mortality. Long noncoding RNAs (lncRNAs) are thought to play a critical role in cancer development. LncRNA NRON, a repressor of activated T-cell nuclear factor (NFAT), has been shown to be dysregulated in many cancer types. However, the clinical significance and molecular mechanism of NRON in bladder cancer is still unknown. Methods: The expression levels of NRON in BC tissues and cell lines were tested by RT-qPCR. Survival analysis was performed to detect the correlation between NRON expression and clinical outcomes in patients with BC. The biological role of NRON in BC cells proliferation and metastasis was examined in vitro and in vivo. Results: The expression of NRON was significantly upregulated in BC specimens and cell lines compared with paired adjacent normal tissues and normal cell lines. The upregulation of NRON in bladder cancer patients was significantly associated with the depth of bladder tumor invasion and poor prognosis. Knockdown of NRON inhibited BC cells proliferation, migration, invasion and tumorigenicity. Furthermore, NRON promoted epithelial-mesenchymal transition (EMT) progression, and NRON-induced EZH2 expression contributed to this process. Conclusion: In conclusion, our results suggested that NRON acted as an oncogene and tumor biomarker for BC.

PCAT-1: A Novel Oncogenic Long Non-Coding RNA in Human Cancers.

Long non-coding RNAs (lncRNAs) are transcripts longer than 200 nucleotides (nts) without obvious protein coding potential. lncRNAs act as multiple roles in biological processes of diseases, especially carcinomas. Prostate cancer associated transcript-1 (PCAT-1) is an oncogenic lncRNA that identified by RNA-Sequence in prostate cancer. High expression of PCAT-1 is observed in different types of cancers, including prostate cancer, colorectal cancer, hepatocellular cancer and gastric cancer. High expressed PCAT-1 is correlated with poor overall survival. Furthermore, PCAT-1 regulates cancer cell proliferation, apoptosis, migration and invasion. Additionally, PCAT-1 is involved in EMT and Wnt/ß-catenin-signaling pathway. In this review, we focus on the implication of PCAT-1 in human cancers.