NR4A1 transcriptionally regulates the differentiation of stem-like CD8+ T cells in the tumor microenvironment.

CD8+ T cells are rendered exhausted in tumor and chronic infection. Among heterogeneous exhausted T cells, a subpopulation of progenitor-like (Tpex) cells have been found important for long-term tumor or pathogen control and are also the main responders in immunotherapy. Using an RFP reporter mouse for the orphan nuclear receptor NR4A1, originally characterized as critical in T cell dysfunction, we discover that the reporter is highly expressed in Tpex cells in tumor and chronic infection. Enforced expression of Nr4a1 promotes Tpex cell accumulation, whereas tumor control is improved after Nr4a1 deletion, associated with increased effector function but decreased long-term maintenance of CD8+ T cells. Integrating chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis, NR4A1 is found to bind and promote the expression of Tpex-related genes, as well as suppress terminal differentiation-associated genes. This study therefore has identified a key role of NR4A1 in Tpex regulation and provides a promising target for immunotherapy.

DRD2 TaqIA polymorphism-related functional connectivity between anterior insula and dorsolateral prefrontal cortex predicts the retention time in heroin-dependent individuals under methadone maintenance treatment.

BACKGROUND: Dopamine receptor D2 (DRD2) TaqIA polymorphism has an influence on addiction treatment response and prognosis by mediating brain dopaminergic system efficacy. Insula is crucial for conscious urges to take drugs and maintain drug use. However, it remains unclear about the contribution of DRD2 TaqIA polymorphism to the regulation of insular on addiction behavioral and its relation with the therapeutic effect of methadone maintenance treatment (MMT). METHODS: 57 male former heroin dependents receiving stable MMT and 49 matched male healthy controls (HC) were enrolled. Salivary genotyping for DRD2 TaqA1 and A2 alleles, brain resting-state functional MRI scan and a 24-month follow-up for collecting illegal-drug-use information was conducted and followed by clustering of functional connectivity (FC) patterns of HC insula, insula subregion parcellation of MMT patients, comparing the whole brain FC maps between the A1 carriers and non-carriers and analyzing the correlation between the genotype-related FC of insula sub-regions with the retention time in MMT patients by Cox regression. RESULTS: Two insula subregions were identified: the anterior insula (AI) and the posterior insula (PI) subregion. The A1 carriers had a reduced FC between the left AI and the right dorsolateral prefrontal cortex (dlPFC) relative to no carriers. And this reduced FC was a poor prognostic factor for the retention time in MMT patients. CONCLUSION: DRD2 TaqIA polymorphism affects the retention time in heroin-dependent individuals under MMT by mediating the functional connectivity strength between left AI and right dlPFC, and the two brain regions are promising therapeutic targets for individualized treatment.

BCL6 promotes a stem-like CD8+ T cell program in cancer via antagonizing BLIMP1.

Overcoming CD8+ T cell exhaustion is critical in cancer immunotherapy. Recently, an intratumor stem/progenitor-like CD8+ T cell (Tprog cell) population that mediates the persistence of antitumor responses has been defined, which can further develop into a terminally differentiated CD8+ T cell (Tterm cell) subpopulation with potent cytotoxic functions. Tprog cells are the main responders to immune checkpoint blockade therapies, yet how extrinsic signals via transcription factors control Tprog cell generation and persistence in tumors is unclear. Here, we found that BCL6 inhibits tumor-specific Tterm cell generation from Tprog cell downstream of TCF1. We show that Bcl6 deficiency reduced the persistence of Tprog cells, without affecting their generation, thus abrogating long-term tumor control. High-level BCL6 expression was observed in tumor-specific T cells in draining lymph nodes (LNs) and was associated with T cell exhaustion. This was observed in TOX+TCF1+ Tprog cells in both LNs and tumors. BCL6 expression in CD8+ T cells was up-regulated by TGF-ß-SMAD2 signaling but down-regulated by the IL-2-STAT5 pathway. Mechanistically, BCL6 transcriptionally repressed the expression of Tterm cell-associated genes and induced those of Tprog cell-related genes, in a manner antagonistic to BLIMP1. Prdm1 deficiency also promoted the Tprog cell program and greatly improved the efficacy of anti-PD-1 therapy. Thus, we identified the TGF-ß-BCL6 and IL-2-BLIMP1 antagonistic pathways in regulation of antitumor CD8+ T cells, which may benefit the development of long-lasting and effective cancer immunotherapy.

Cell autonomous expression of BCL6 is required to maintain lineage identity of mouse CCR6+ ILC3s.

Innate lymphoid cells (ILC) are similar to T helper (Th) cells in expression of cytokines and transcription factors. For example, RORγt is the lineage-specific transcription factor for both ILC3 and Th17 cells. However, the ILC counterpart for BCL6-expressing T follicular helper (Tfh) cells has not been defined. Here, we report that in the ILC compartment, BCL6 is selectively co-expressed with not only CXCR5 but also RORγt and CCR6 in ILC3 from multiple tissues. BCL6-deficient ILC3 produces enhanced levels of IL-17A and IL-22. More importantly, phenotypic and single-cell ATAC-seq analysis show that absence of BCL6 in mature ILC3 increases the numbers of ILC1 and transitional cells co-expressing ILC3 and ILC1 marker genes. A lineage-tracing experiment further reveals BCL6+ ILC3 to ILC1 trans-differentiation under steady state. Finally, microbiota promote BCL6 expression in colonic CCR6+ ILC3 and thus reinforce their stability. Collectively, our data have demonstrated that CCR6+ ILC3 have both Th17 and Tfh programs and that BCL6 expression in these cells functions to maintain their lineage identity.

STAT3 regulates CD8+ T cell differentiation and functions in cancer and acute infection.

In cancer, persistent antigens drive CD8+ T cell differentiation into exhausted progenitor (Texprog) and terminally exhausted (Texterm) cells. However, how the extrinsic and intrinsic regulatory mechanisms cooperate during this process still remains not well understood. Here, we found that STAT3 signaling plays essential roles in promoting intratumor Texterm cell development by enhancing their effector functions and survival, which results in better tumor control. In tumor microenvironments, STAT3 is predominantly activated by IL-10 and IL-21, but not IL-6. Besides, STAT3 also plays critical roles in the development and function of terminally differentiated effector CD8+ T cells in acute infection. Mechanistically, STAT3 transcriptionally promotes the expression of effector function-related genes, while it suppresses those expressed by the progenitor Tex subset. Moreover, STAT3 functions in collaboration with BATF and IRF4 to mediate chromatin activation at the effector gene loci. Thus, we have elucidated the roles of STAT3 signaling in terminally differentiated CD8+ T cell development, especially in cancer, which benefits the development of more effective immunotherapies against tumors.

[Retracted] MicroRNA­760 inhibits cell proliferation and invasion of colorectal cancer by targeting the SP1­mediated PTEN/AKT signalling pathway.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that certain of the cell migration and invasion assay data shown in Figs. 2C and 5C were strikingly similar to data appearing in different form in other articles by different authors. Owing to the fact that the contentious data in the above article had already been published elsewhere, or were already under consideration for publication, prior to its submission to Molecular Medicine Reports, the Editor has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a satisfactory reply. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in Molecular Medicine Reports 16: 9692­9700, 2017; DOI: 10.3892/mmr.2017.7814].

Ultrasound Entropy Imaging for Detection and Monitoring of Thermal Lesion During Microwave Ablation of Liver.

Ultrasonic B-mode imaging offers non-invasive and real-time monitoring of thermal ablation treatment in clinical use, however it faces challenges of moderate lesion-normal contrast and detection accuracy. Quantitative ultrasound imaging techniques have been proposed as promising tools to evaluate the microstructure of ablated tissue. In this study, we introduced Shannon entropy, a non-model based statistical measurement of disorder, to quantitatively detect and monitor microwave-induced ablation in porcine livers. Performance of typical Shannon entropy (TSE), weighted Shannon entropy (WSE), and horizontally normalized Shannon entropy (hNSE) were explored and compared with conventional B-mode imaging. TSE estimated from non-normalized probability distribution histograms was found to have insufficient discernibility of different disorder of data. WSE that improves from TSE by adding signal amplitudes as weights obtained area under receiver operating characteristic (AUROC) curve of 0.895, whereas it underestimated the periphery of lesion region. hNSE provided superior ablated area prediction with the correlation coefficient of 0.90 against ground truth, AUROC of 0.868, and remarkable lesion-normal contrast with contrast-to-noise ratio of 5.86 which was significantly higher than other imaging methods. Data distributions shown in horizontally normalized probability distribution histograms indicated that the disorder of backscattered envelope signal from ablated region increased as treatment went on. These findings suggest that hNSE imaging could be a promising technique to assist ultrasound guided percutaneous thermal ablation.

RORα is critical for mTORC1 activity in T cell-mediated colitis.

Inflammatory bowel disease (IBD) is multi-factorial chronic intestinal inflammation driven by pathogenic T cells, among which a large portion of patients are resistant to current anti-inflammatory regimes. The mechanisms underlying colitis pathogenicity and drug resistance are not fully understood. Here, we demonstrate that RORα is highly expressed in active UC patients, particularly in those non-responsive to anti-TNF treatment. Rorα deficiency in CD4+ T cells greatly reduced colitis development. Mechanistically, RORα regulated T cell infiltration in colon and inhibited T cell apoptosis. Meanwhile, genome-wide occupancy and transcriptome analysis revealed that RORα promoted mTORC1 activation. mTORC1 signaling, also hyperactivated in active UC patients, is necessary for T cell-mediated colitis. Our results thus demonstrate a crucial role of the RORα-mTORC1 axis in CD4+ T cells in promoting IBD, which may be targeted in human patients.

Interleukin-17D regulates group 3 innate lymphoid cell function through its receptor CD93.

The interleukin (IL)-17 family, consisting of six members, promotes host defense but can in some context promote the development of autoimmune disease. Here, we examined the role of IL-17D, a poorly understood member in the IL-17 family. IL-17D was expressed primarily by colonic epithelial cells. Il17d-/- mice were more susceptible to acute colitis, bacterial infection and experimentally induced colon cancer than their wildtype counterparts. Il17d deficiency impaired IL-22 production by group 3 innate lymphoid cells (ILC3s) and reduced expression of IL-22-dependent antimicrobial peptides, RegIIIß and RegIIIγ, in colon tissue at steady state and in colitis; this was associated with changes in microbial composition and dysbiosis. Protein purification studies revealed that IL-17D bound not canonical IL-17 receptors, but rather CD93, a glycoprotein expressed on mature ILC3s. Mice lacking Cd93 in ILC3s exhibited impaired IL-22 production and aggravated colonic inflammation in experimental colitis. Thus, an IL-17D-CD93 axis regulates ILC3 function to preserve intestinal homeostasis.

Identification of a three-long non-coding RNA signature for predicting survival of temozolomide-treated isocitrate dehydrogenase mutant low-grade gliomas.

Temozolomide (TMZ) is the major chemotherapy agent in glioma, and isocitrate dehydrogenase (IDH) is a well-known prognostic marker in glioma. O6-methylguanine-DNA methyltransferase promoter methylation (MGMTmethyl) is a predictive biomarker in overall gliomas rather than in IDH mutant gliomas. To discover effective biomarkers that could predict TMZ efficacy in IDH mutant low-grade gliomas (LGGs), we retrieved data of IDH mutant LGGs from TMZ arm of the EORTC22033-26033 trial as the training-set (n = 83), analyzed correlations between long non-coding RNAs (lncRNAs) and progression-free survival (PFS) using Lasso-Cox regression, and created a risk score (RS) to stratify patients. We identified a three-lncRNA signature in TMZ-treated IDH mutant LGGs. All of the three lncRNAs, as well as the RS derived, were significantly correlated with PFS. Patients were classified into high-risk and low-risk groups according to RS. PFS of the high-risk group was significantly worse than that of the low-risk group (P < 0.001). AUCs of the three-, four-, and five-year survival probability predicted by RS were 0.73, 0.79, and 0.76, respectively. The predictive role of the three-lncRNA signature was further validated in an independent testing-set, the TCGA-LGGs, which resulted in a significantly worse PFS (P < 0.001) in the high-risk group. Three-, four-, and five-year survival probabilities predicted by RS were 0.65, 0.69, and 0.84, respectively. Functions of these three lncRNAs involve cell proliferation and differentiation, predicted by their targeting cancer genes. Conclusively, we created a scoring model based on the expression of three lncRNAs, which can effectively predict the survival of IDH mutant LGGs treated with TMZ.

LncRNA XIST modulates HIF-1A/AXL signaling pathway by inhibiting miR-93-5p in colorectal cancer.

BACKGROUND: Long noncoding RNA (LncRNA) XIST is one of the genes that exists in different types of cancers. Earlier researches showed that XIST can advance the progression of colorectal cancer. Nevertheless, the potential molecular mechanism of XIST in combination with miR-93-5p has not been explored in colorectal cancer. METHODS: We performed qRT-PCR to explore the level of XIST. And a serious experiments in vitro and in vivo were performed to explore the function of XIST. The relationship between XIST/HIF-1A and miR-93-5p was confirmed by RIP and dual-luciferase assays. RESULTS: In the present research, our team demonstrated the upregulation of XIST expression, which was related to tumor progression, and the downregulation of miR-93-5p in cells and tissues of colorectal cancer. XIST is the competitive endogenous RNA of miR-93-5p to promote HIF-1A, and then the upregulated AXL level facilitates the EMT process, migration, and proliferation of colorectal cancer. At last, we proved that XIST enhanced the in vivo and in vitro activities of colorectal cancer by regulating AXL signaling. CONCLUSION: In summary, the above results indicate that XIST promotes colorectal cancer tumorigenesis by regulating miR-93-5p/HIF-1A/AXL signaling pathway, which will supply a novel perspective to diagnose and treat colorectal cancer disease.

Tumor-expressed B7-H3 mediates the inhibition of antitumor T-cell functions in ovarian cancer insensitive to PD-1 blockade therapy.

Although PD-L1/PD-1 blockade therapy has been approved to treat many types of cancers, the majority of patients with solid tumors do not respond well, but the underlying reason remains unclear. Here, we studied ovarian cancer (OvCa), a tumor type generally resistant to current immunotherapies, to investigate PD-1-independent immunosuppression. We found that PD-L1 was not highly expressed in the tumor microenvironment (TME) of human OvCa. Instead, B7-H3, another checkpoint molecule, was highly expressed by both tumor cells and tumor-infiltrating antigen-presenting cells (APCs), which correlated with T-cell exhaustion in patients. Using ID8 OvCa mouse models, we found that B7-H3 expressed on tumor cells, but not host cells, had a dominant role in suppressing antitumor immunity. Therapeutically, B7-H3 blockade, but not PD-1 blockade, prolonged the survival of ID8 tumor-bearing mice. Collectively, our results demonstrate that tumor-expressed B7-H3 inhibits the function of CD8+ T cells and suggest that B7-H3 may be a target in patients who are not responsive to PD-L1/PD-1 inhibition, particularly OvCa patients.

PTPRF as a novel tumor suppressor through deactivation of ERK1/2 signaling in gastric adenocarcinoma.

BACKGROUND: Protein tyrosine phosphatase, receptor type F (PTPRF) is an important phosphatase playing roles in regulating cell growth, differentiation and oncogenic transformation. Overexpression of PTPRF has been observed in non-small cell lung cancer, but its clinical significance in other malignancies is still unknown. METHODS: We explored the expression pattern of PTPRF in gastric adenocarcinoma by using RT-qPCR and immunohistochemistry staining. The clinical significance of PTPRF was evaluated by univariate and multivariate analyses. Furthermore, the signaling pathways downstream of PTPRF was investigated by knockdown and overexpression assays combined with cellular studies. RESULTS: We found a remarkable down-regulation of PTPRF in gastric adenocarcinomas, which was significantly associated with advanced tumor TNM stages. Survival analysis showed that lower PTPRF level indicated a poorer overall survival of gastric adenocarcinoma patients. By conducting knockdown and overexpression studies in gastric adenocarcinoma cells, we revealed the role of PTPRF on inhibiting extracellular signal-regulated kinase-1/2 (ERK1/2) phosphorylation and its downstream signaling. Consistent with clinical findings, cellular results demonstrated that overexpressing PTPRF can significantly inhibit tumor migration and invasion, while silencing PTPRF showed opposite effects. CONCLUSION: In conclusion, patients with lower PTPRF expression in gastric adenocarcinoma tissues were more predisposed to advanced tumor stage and unfavorable prognosis.

MicroRNA­760 inhibits cell proliferation and invasion of colorectal cancer by targeting the SP1­mediated PTEN/AKT signalling pathway.

Colorectal cancer (CRC), one of the most commonly diagnosed types of cancer worldwide, is the third most prevalent and fourth most frequent cause of cancer­related mortality. Dysregulated microRNAs (miRNAs) have potential regulatory roles in the development and progression of various cancer types. Therefore, the investigation of the miRNAs involved in CRC formation and progression may lead to the development of highly effective therapeutic strategies for CRC. In the present study, miRNA­760 (miR­760) was frequently downregulated in CRC tissues and cell lines. The low levels of miR­760 expression were significantly correlated with the tumor size, lymph node metastasis and TNM stage of CRC. Functional assays revealed that restoring miR­760 expression inhibited CRC cell proliferation and invasion in vitro. The results of bioinformatics analysis, luciferase reporter assay, reverse transcription­quantitative polymerase chain reaction and western blot analysis suggested that specificity protein 1 (SP1) is a direct target of miR­760 in CRC. The high expression of SP1 in CRC tissues was inversely correlated with the expression of miR­760. Rescue experiments demonstrated that enforced SP1 expression rescued the tumor­suppressing effects of miR­760 on CRC cell proliferation and invasion. In addition, miR­760 overexpression is involved in the regulation of the PTEN/AKT signalling pathway. Collectively, the present data demonstrated that miR­760 directly targets SP1 to inactivate the PTEN/AKT signalling pathway, thus implicating miR­760 in the regulation of CRC cell proliferation and invasion. Therefore, miR­760 may be a novel biomarker and therapeutic target for CRC.

Expression of Fibroblast Growth Factor 10 Is Correlated with Poor Prognosis in Gastric Adenocarcinoma.

Fibroblast growth factor receptor 2 (FGFR2) has been proved to be a significant prognostic factor and a potential therapeutic target in several types of cancer, including gastric cancer. FGFR2 consists two isoforms: FGFR2-IIIb and FGFR2-IIIc, which can be stimulated by different ligands and trigger different downstream signaling pathways. As a specific ligand to FGFR2-IIIb, fibroblast growth factor 10 (FGF10) is expressed in the gastric mesenchyme cell and is involved in stomach development and morphogenesis, but its expression and clinical significance is not well elucidated in gastric cancer. We analyzed FGF10 expression by immunohistochemistry in 178 samples of gastric adenocarcinoma (134 male and 44 female patients, with the average age of 63.2 years old and the average follow-up of 21.6 months). Using the arbitrarily scoring method based on positive cell percentage and staining intensity, we sub-divided the patients into FGF10 high-expression group (58 patients) and low-expression group (120 patients). We thus found that FGF10 expression is significantly associated with lymph node invasion (P = 0.004) and distant metastasis (P = 0.032). Importantly, FGF10 expression is an independent unfavorable prognostic factor (P = 0.042). Moreover, FGF10 knockdown significantly decreased the migration of cultured gastric adenocarcinoma cells, suggesting that FGF10 could promote the invasion of gastric adenocarcinoma. In conclusion, FGF10 expression was identified as a poor prognostic biomarker in gastric adenocarcinoma, and FGF10 could promote the invasion of gastric cancer cells. We suggest that FGF10 could be a potential and promising drug target in gastric adenocarcinoma.

Intraoperative sentinel lymph node mapping guides laparoscopic-assisted distal gastrectomy for distal gastric cancer.

AIMS: The aim of this retrospective study is to explore the effects of sentinel lymph node (SLN) mapping guided laparoscopic-assisted distal gastrectomy (LADG) for distal gastric cancer. METHODS: Two hundred patients were enrolled in this study. One hundred and one patients undergoing SLN guided LADG were designated as the SLN group. Ninety-nine patients having conventional LADG with D1 or D2 lymph node dissection were designated as the control group. Intraoperative and postoperative indicators such as the number of lymph nodes dissected, intraoperative and postoperative conditions, flow cytometry analysis of T lymphocyte subsets and natural killer (NK) cells, survival rates, recurrence rates and postoperative complications were investigated between these two groups. RESULTS: The number of lymph nodes dissected in the SLN group was significantly lesser than that in the control group. Furthermore, in the SLN group, the patients achieved better immunization status, improved intraoperative and postoperative conditions and decreased postoperative complications. There were no significant differences were found in the positive lymph nodes detected, the distance between proximal and distal cutting edge, postoperative survival or recurrence rates. CONCLUSIONS: SLN guided LADG for gastric cancer is a safe and effective method and could achieve an equal clinical effect as traditional laparoscopic D1 or D2 radical operation with less operation trauma and better recovery.

Expression of matrix metalloproteinase-9, cyclooxygenase-2 and vascular endothelial growth factor are increased in gastrointestinal stromal tumors.

This study is to investigate the expression of matrix metalloproteinase-9 (MMP-9), cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) in gastrointestinal stromal tumor (GIST). Immunohistochemistry was performed to detect the expression of MMP-9, COX-2 and VEGF. The expression of MMP-9, COX-2 and VEGF was compared among different clinicopathological features of GIST. Spearman rank correlation analysis was conducted to analyze the correlation among MMP-9, COX-2 and VEGF. The positive expression rates of MMP-9, COX-2 and VEGF were 76.9%, 84.6% and 82.7%. The expression levels of MMP-9, COX-2 and VEGF were significantly different among the clinicopathological features of growth pattern, tumor diameter, metastasis, mitotic count and central necrosis (P < 0.05). Their expression levels were higher in GIST tissues with higher levels of malignancy, tumor size, metastasis, mitotic count and central necrosis. However, their expression levels were not significantly different among age, gender, primary tumor site or CD117 expression. Additionally, there were positive correlations between COX-2 and VEGF (r = 0.612, P < 0.01), between COX-2 and MMP-9 (r = 0.592, P < 0.05), and between MMP-9 and VEGF (r = 0.690, P < 0.01). MMP-9, COX-2 and VEGF expression levels are increased in GIST tissues and related with clinicopathological features of GIST.

Expression and clinical significance of fibroblast growth factor 1 in gastric adenocarcinoma.

BACKGROUND: The clinical significance of fibroblast growth factor 1 (FGF1) has been revealed in several cancers, including ovarian cancer, breast cancer, and bladder cancer. However, the clinical significance of FGF1 in gastric adenocarcinoma has not been explored. PATIENTS AND METHODS: In our experiments, we systematically evaluated FGF1 expression in 178 cases of gastric adenocarcinoma with immunohistochemistry, and subsequently analyzed the correlation between FGF1 expression and clinicopathologic features. Moreover, FGF1 expression in tumor tissue and corresponding adjacent tissue was detected and compared by real-time polymerase chain reaction. The Kaplan-Meier method and the Cox-regression model were used with univariate and multivariate analysis, respectively, to evaluate the prognostic value of FGF1 in gastric adenocarcinoma. RESULTS: Higher FGF1 expression rate is 56.7% (101/178) in gastric adenocarcinoma. FGF1 expression in gastric adenocarcinoma was significantly higher than adjacent tissue (P<0.0001). Expression of FGF1 is significantly associated with lymph node invasion (P<0.001), distant metastasis (P=0.013), and differentiation (P=0.015). Moreover, FGF1 overexpression was closely related to unfavorable overall survival rate (P=0.021), and can be identified to be an independent unfavorable prognostic factor (P=0.004). CONCLUSION: FGF1 is an independent prognostic factor, indicating that FGF1 could be a potential molecular drug target in gastric adenocarcinoma.

Background eliminated signal-on electrochemical aptasensing platform for highly sensitive detection of protein.

Using platelet-derived growth factor B chain dimer (PDGF-BB) as the model target, a background current eliminated electrochemical aptameric sensing platform for highly sensitive and signal-on detection of protein is proposed in this paper. Successful fabrication of the biosensor depends on ingenious design of aptamer probe, which contains the aptamer sequence for PDGF-BB and the recognition sequence for EcoRI endonuclease. In the absence of PDGF-BB, the ferrocene labeled aptamer probe folds into a hairpin structure and forms a recognition site for EcoRI. By treatment with endonuclease, the specific and cleavable double-stranded region is cut off and redox-active ferrocene molecule is removed from the electrode surface, and almost no peak current is observed. When binding with target protein, the designed aptamer probe changes its conformation and dissociates the recognition double strand. The integrated aptamer probe is maintained when exposing to EcoRI endonuclease, resulting in obvious peak current. Therefore, a signal-on and sensitive sensing strategy for PDGF-BB detection is fabricated with eliminated background current. Under the optimized experimental conditions, a wide linear response range of 4 orders of magnitude from 20pgmL(-1) to 200ngmL(-1) is achieved with a detection limit of 10pgmL(-1). Moreover, the present aptameric platform is universal for the analysis of a broad range of target molecules of interest by changing and designing the sequence of aptamer probe.