Publications by authors named "Huaizhi Wang"

67 Publications

N-methyladenosine (mA) in pancreatic cancer: Regulatory mechanisms and future direction.

Int J Biol Sci 2021 4;17(9):2323-2335. Epub 2021 Jun 4.

Department of Pathophysiology, College of High Altitude, Army Medical University (Third Military Medical University), Chongqing 400038, PR China.

N-methyladenosine (mA), the most abundant RNA modification in eukaryotes, plays a pivotal role in regulating many cellular and biological processes. Aberrant mA modification has recently been involved in carcinogenesis in various cancers, including pancreatic cancer. Pancreatic cancer is one of the deadliest cancers. It is a heterogeneous malignant disease characterized by a plethora of diverse genetic and epigenetic events. Increasing evidence suggests that dysregulation of mA regulatory factors, such as methyltransferases, demethylases, and mA-binding proteins, profoundly affects the development and progression of pancreatic cancer. In addition, mA regulators and mA target transcripts may be promising early diagnostic and prognostic cancer biomarkers, as well as therapeutic targets. In this review, we highlight the biological functions and mechanisms of mA in pancreatic cancer and discuss the potential of mA modification in clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/ijbs.60115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241726PMC
June 2021

Corrigendum to "Metabolomics identified new biomarkers for the precise diagnosis of pancreatic cancer and associated tissue metastasis" [Pharmacol. Res. 156 (June 2020) 104805].

Pharmacol Res 2021 Jul 18;169:105657. Epub 2021 May 18.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China; Laboratory for Functional Metabolomics Science, Shanghai Jiao Tong University, Shanghai 200240, China. Electronic address:

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2021.105657DOI Listing
July 2021

Probiotics alleviate depressive behavior in chronic unpredictable mild stress rat models by remodeling intestinal flora.

Neuroreport 2021 May;32(8):686-693

Department of Psychiatry.

Objective: To explore the effects of probiotics on depressive behavior in a chronic unpredictable mild stress (CUMS) rat model by remodeling intestinal flora.

Methods: Twenty-four male SD rats aged 6-8 weeks were randomly divided into four groups: control group, depression group (CUMS), depression+paroxetine group (Paro) and depression+probiotics group (Pro). Sucrose preference, open field and forced swimming tests were used to assess depression-like behavior in rats. ELISA was used to detect the levels of adrenocorticotropic hormone (ACTH), and corticosterone, norepinephrine and 5-hydroxytryptamine in rat serum. Real-time PCR was used to determine the changes of Lactobacillus, Bifidobacterium, Enterococcus faecalis and Escherichia coli in rat cecum.

Results: Compared with the control group, CUMS led to significant decreases of body weight, total traveled distance, duration in central area, immobility time, norepinephrine and 5-hydroxytryptamine contents in hippocampal tissues, as well as Lactobacillus and Bifidobacterium in the cecum. It also resulted in marked increases of the contents of E. faecalis and E. coli in the cecum, ACTH and corticosterone contents in the serum of rats. Paroxetine and probiotic treatment each diminished or prevented these changes.

Conclusion: By remodeling intestinal flora, probiotics can reduce the CUMS-induced depressive behavior of rats, increase the levels of norepinephrine and 5-hydroxytryptamine, and inhibit the expression of ACTH and corticosterone. Significantly, the effect of both paroxetine and probiotic on microorganisms is similar.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/WNR.0000000000001637DOI Listing
May 2021

TMPRSS4 Promotes Cell Proliferation and Inhibits Apoptosis in Pancreatic Ductal Adenocarcinoma by Activating ERK1/2 Signaling Pathway.

Front Oncol 2021 18;11:628353. Epub 2021 Mar 18.

Department of Hepatobiliary Surgery I, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Transmembrane protease serine 4 (TMPRSS4) is upregulated in various kinds of human cancers, including pancreatic cancer. However, its biological function in pancreatic ductal adenocarcinoma (PDAC) remains unclear. In the current study, real-time qPCR, immunohistochemical staining, Western blotting, and database (Cancer Genome Atlas and Gene Expression) analysis revealed remarkable overexpression of TMPRSS4 in PDAC tissue as compared to non-tumor tissue. The TMPRSS4 overexpression was associated with poor prognosis of PDAC patients. Moreover, multivariate analysis revealed that TMPRSS4 serves as an independent risk factor in PDAC. We performed gain-and loss-of-function analysis and found that TMPRSS4 promotes cellular proliferation and inhibits apoptosis of PDAC cells both and . Furthermore, we showed that TMPRSS4 might promote cell proliferation and inhibit apoptosis through activating ERK1/2 signaling pathway in pancreatic cancer cells. These findings were validated by using ERK1/2 phosphorylation inhibitor SCH772984 both and . Taken together, this study suggests that TMPRSS4 is a proto-oncogene, which promotes initiation and progression of PDAC by controlling cell proliferation and apoptosis. Our findings indicate that TMPRSS4 could be a promising prognostic biomarker and a therapeutic target for the treatment of pancreatic cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2021.628353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8012900PMC
March 2021

CRL4A degrades DNA-PKcs to modulate NHEJ repair and induce genomic instability and subsequent malignant transformation.

Oncogene 2021 Mar 24;40(11):2096-2111. Epub 2021 Feb 24.

Key Laboratory for Experimental Teratology of the Ministry of Education, Department of Cell Biology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Genomic instability induced by DNA damage and improper DNA damage repair is one of the main causes of malignant transformation and tumorigenesis. DNA double strand breaks (DSBs) are the most detrimental form of DNA damage, and nonhomologous end-joining (NHEJ) mechanisms play dominant and priority roles in initiating DSB repair. A well-studied oncogene, the ubiquitin ligase Cullin 4A (CUL4A), is reported to be recruited to DSB sites in genomic DNA, but whether it regulates NHEJ mechanisms of DSB repair is unclear. Here, we discovered that the CUL4A-DTL ligase complex targeted the DNA-PKcs protein in the NHEJ repair pathway for nuclear degradation. Overexpression of either CUL4A or DTL reduced NHEJ repair efficiency and subsequently increased the accumulation of DSBs. Moreover, we demonstrated that overexpression of either CUL4A or DTL in normal cells led to genomic instability and malignant proliferation. Consistent with the in vitro findings, in human precancerous lesions, CUL4A expression gradually increased with increasing malignant tendency and was negatively correlated with DNA-PKcs and positively correlated with γ-H2AX expression. Collectively, this study provided strong evidence that the CUL4A-DTL axis increases genomic instability and enhances the subsequent malignant transformation of normal cells by inhibiting NHEJ repair. These results also suggested that CUL4A may be a prognostic marker of precancerous lesions and a potential therapeutic target in cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41388-021-01690-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979543PMC
March 2021

Operando Magnetometry Probing the Charge Storage Mechanism of CoO Lithium-Ion Batteries.

Adv Mater 2021 Mar 12;33(12):e2006629. Epub 2021 Feb 12.

College of Physics, Center for Marine Observation and Communications, Qingdao University, Qingdao, 266071, China.

Cobalt oxide (CoO) is a promising electrode for high-energy-density Li-ion batteries (LIBs), where the charge storage is believed to take place solely during the electrochemical oxidation/reduction processes. However, this simple picture has been increasingly challenged by reported anomalously large storage capacities, indicating the existence of undiscovered extra charge reservoirs inside the system. Here, an advanced operando magnetometry technology is employed to monitor the magnetization variation of the CoO LIBs in real time and, in this particular system, it is clearly demonstrated that the anomalous capacity is associated with both the reversible formation of a spin capacitor and the growth of a polymeric film at low voltages. Furthermore, operando magnetometry provides direct evidence of the catalytic role of metallic Co in assisting the polymeric film formation. These critical findings help pave the way for better understanding of the charge storage mechanisms of transition-metal oxides and further utilizing them to design novel electrode materials.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/adma.202006629DOI Listing
March 2021

Alteration of tumor-associated macrophage subtypes mediated by KRT6A in pancreatic ductal adenocarcinoma.

Aging (Albany NY) 2020 11 18;12(22):23217-23232. Epub 2020 Nov 18.

Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 401120, P R China.

Pancreatic ductal adenocarcinoma (PDAC) is severely affecting the health and lives of patients. Clarifying the composition and regulatory factors of tumor immune microenvironment (TIME) is helpful for the treatment of PDAC. We analyzed the unique TIMEs and gene expression patterns between PDAC and adjacent normal tissue (ANT) using Gene Expression Omnibus (GEO) to find new immunotherapy targets. The Cancer Genome Atlas (TCGA) datasets were used to elucidate the possible mechanism of which tumor-associated macrophages (TAMs) changed in PDAC. We found that the composition of TAMs subtypes, including M0, M1, and M2, was different between PDAC and ANT, which was validated in recently published single-cell RNA-seq data. Many immune cells interacted with each other to affect the TIME. There were many DEGs enriched in some pathways that could potentially change the immune cell composition. KRT6A was found to be a DEG between PDAC and ANT that overlapped with DEGs between the M0-high group and the M0-low group in TCGA datasets, and it might alter and regulate TAMs via a collection of genes including COL5A2, COL1A2, MIR3606, SPARC, and COL6A3. TAMs, which could be a target of immunotherapy, might be influenced by genes through KRT6A and indicate an undesirable prognosis in PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.104091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746340PMC
November 2020

Characterization of Oral Microbiome and Exploration of Potential Biomarkers in Patients with Pancreatic Cancer.

Biomed Res Int 2020 31;2020:4712498. Epub 2020 Oct 31.

Shenzhen Baoan Women's and Children's Hospital, Jinan University, 518102 Shenzhen, China.

Pancreatic cancer (PC) is highly malignant and lacks an effective therapeutic schedule, hence that early diagnosis is of great importance to achieve a good prognosis. Oral bacteria have been proved to be associated with pancreatic cancer, but the specific mechanism has not been comprehensively illustrated. In our study, thirty-seven saliva samples in total were collected with ten from PC patients, seventeen from benign pancreatic disease (BPD) patients, and ten from healthy controls (HC). The oral bacterial community of HC, PC, and BPD groups was profiled by 16S rDNA high-throughput sequencing and bioinformatic methods. As shown by Simpson, Inverse Simpson, Shannon and Heip, oral microbiome diversity of HC, BPD and PC groups is in increasing order with the BPD and PC groups significantly higher than the HC group. Principal coordinate analysis (PCoA) suggested that grouping by PC, BPD and HC was statistically significant. The linear discriminant analysis effect size (LEfSe) identified high concentrations of and low concentrations of as specific risk factors for PC. Furthermore, predicted functions showed changes such as RNA processing and modification as well as the pathway of NOD-like receptor signaling occurred in both PC and HC groups. Conclusively, our findings have confirmed the destruction of oral bacterial community balance among patients with PC and BPD and indicated the potential of and as diagnostic biomarkers of PC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/4712498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652608PMC
April 2021

Upregulated GDF-15 expression facilitates pancreatic ductal adenocarcinoma progression through orphan receptor GFRAL.

Aging (Albany NY) 2020 11 17;12(22):22564-22581. Epub 2020 Nov 17.

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University (Third Military Medical University), Chongqing 400038, P. R. China.

Growth and differentiation factor 15 (GDF-15) has been studied as an important hallmark of cancer. However, the receptor of GDF-15 in pancreatic cancer cell remains unclear. Here, we investigated its biological effects in pancreatic ductal adenocarcinoma (PDAC). We found that aberrant GDF-15 expression positively correlated with poor survival of PDAC patients. GDF-15 protein enhanced tumor cell proliferation in two pancreatic cancer lines, AsPC-1 and BxPC-3. Knockdown GDF-15 attenuated its biological function and reduced PDAC cell tumorigenesis upon xenotransplantation into nude mice. Moreover, we identified that glial-derived neurotropic factor family receptor α-like (GFRAL) was upregulated in PDAC tissues and positively correlated with GDF-15 expression. High GFRAL expression was significantly associated with poor survival in PDAC patients. Furthermore, we identified that the biological effects of GDF-15 are mediated by its receptor GFRAL which is present in PDAC cells. After overexpression GFRAL in pancreatic cancer cells, the effect of GDF-15 was significantly enhanced. Overall, our findings demonstrated that the GDF-15 secreted by PDAC cells, binds to GFRAL, itself localized in PDAC cells, to promote cancer cell growth and metastasis through the GDF-15/GFRAL signaling pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.103830DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746332PMC
November 2020

Establishing and validating a pathway prognostic signature in pancreatic cancer based on miRNA and mRNA sets using GSVA.

Aging (Albany NY) 2020 11 10;12(22):22840-22858. Epub 2020 Nov 10.

Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 401120, P R China.

Pancreatic cancer (PC) is a severe disease with the highest mortality rate among various cancers. It is urgent to find an effective and accurate way to predict the survival of PC patients. Gene set variation analysis (GSVA) was used to establish and validate a miRNA set-based pathway prognostic signature for PC (miPPSPC) and a mRNA set-based pathway prognostic signature for PC (mPPSPC) in independent datasets. An optimized miPPSPC was constructed by combining clinical parameters. The miPPSPC, optimized miPPSPC and mPPSPC were established and validated to predict the survival of PC patients and showed excellent predictive ability. Four metabolic pathways and one oxidative stress pathway were identified in the miPPSPC, whereas linoleic acid metabolism and the pentose phosphate pathway were identified in the mPPSPC. Key factors of the pentose phosphate pathway and linoleic acid metabolism, G6PD and CYP2C8/9/18/19, respectively, are related to the survival of PC patients according to our tissue microarray. Thus, the miPPSPC, optimized miPPSPC and mPPSPC can predict the survival of PC patients efficiently and precisely. The metabolic and oxidative stress pathways may participate in PC progression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18632/aging.103965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7746356PMC
November 2020

Integration of transcriptome and cistrome analysis identifies RUNX1-target genes involved in pancreatic cancer proliferation.

Genomics 2020 11 13;112(6):5343-5355. Epub 2020 Nov 13.

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, PR China; Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing, PR China. Electronic address:

The extremely high proliferation rate of tumor cells contributes to pancreatic cancer (PC) progression. Runt-related transcription factor 1(RUNX1), a key factor in hematopoiesis that was correlated with tumor progression. However, the role of RUNX1 in PC proliferation was still unclear. We found that RUNX1 was significantly upregulated in PC tissues and its expression was negatively associated with prognosis of PC patients in a multicenter analysis according to immunohistochemical (IHC). RUNX1 downregulation in PC resulted in a significantly reduced cell proliferation rate, which was consistent with in vivo subcutaneous tumor formation assay results. RNA-seq and ChIP-seq results revealed that a portion of target genes, including HAP1, GPRC5B, PTPN21, VHL and EN2, were regulated by RUNX1, a finding successfully validated by ChIP-qPCR, qRT-PCR and Western blot. Subsequently, IHC and proliferation assays showed these target genes to be dysregulated in PC, affecting tumor growth. Our data suggest that RUNX1 plays an oncogenic role in tumor proliferation and is a potential prognostic biomarker and therapeutic target for PC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ygeno.2020.11.010DOI Listing
November 2020

Methylation-mediated LINC00261 suppresses pancreatic cancer progression by epigenetically inhibiting c-Myc transcription.

Theranostics 2020 25;10(23):10634-10651. Epub 2020 Aug 25.

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P. R. China.

Due to the limitations of strategies for its early diagnosis and treatment, pancreatic cancer (PC) remains a substantial human health threat. We previously discovered a methylation-mediated lncRNA, LINC00261, which is downregulated in PC tissues. However, the underlying role of LINC00261 in PC remains largely unknown. Quantitative real-time PCR and in situ hybridization were performed to evaluate the expression levels of LINC00261 in PC, adjacent nontumor and normal pancreas tissues. The clinical significance of LINC00261 was assessed in multicenter PC samples. The functions of LINC00261 in PC were investigated by gain- and loss-of-function assays and . Potential downstream pathways and mechanisms were explored via RNA sequencing and bioinformatic analyses. RNA immunoprecipitation and chromatin immunoprecipitation assays were used to validate the underlying mechanisms. Pyrosequencing and targeted demethylation of the LINC00261 promoter were performed to explore the upstream epigenetic mechanisms and therapeutic potential. LINC00261 was significantly downregulated in PC tissues, and its expression was positively associated with the prognosis of PC patients. Phenotypic studies indicated that LINC00261 overexpression significantly suppressed PC cell proliferation, migration and metastasis and . c-Myc was identified as a downstream target of LINC00261. LINC00261 repressed c-Myc transcription by physically interacting and binding with the bromo domain of p300/CBP, preventing the recruitment of p300/CBP to the promoter region of c-Myc and decreasing the H3K27Ac level. Moreover, the methylation level of the LINC00261 promoter was high in PC tissues and was correlated with poor prognosis. Targeted demethylation of the LINC00261 promoter inhibited PC progression both and . Our findings indicate that methylation-mediated LINC00261 suppresses PC progression by epigenetically repressing c-Myc expression. These findings expand the therapeutic potential of LINC00261, possibly providing evidence to support the development of epigenetic drugs or therapeutic strategies. This research adds further insights into the etiology of PC and indicates that LINC00261 may be a prognostic and therapeutic target in PC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7150/thno.44278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7482811PMC
June 2021

The Use of Values WNR and GNR to Distinguish between and Diagnose Different Types of Pancreatitis.

Mol Ther Methods Clin Dev 2020 Sep 22;18:7-14. Epub 2020 May 22.

Institute of Immunology, PLA, Army Medical University, Chongqing 400038, China.

There is no effective serologic parameter to distinguish different types of pancreatitis now. To distinguish between acute pancreatitis (AP) and acute exacerbations of chronic pancreatitis (CP) and to determine whether fibrosis occurs in CP, we evaluated the ability to produce white blood cells (WBCs), the neutrophil-to-retinol-binding protein (RBP) ratio (called the WNR), the product of the gamma-glutamyl transpeptidase (GGT) level, and the 5'-nucleotide-to-RBP ratio (called the GNR). We evaluated the newly proposed difference index RBP and analyzed the effectiveness of the WNR and GNR in 691 patients with pancreatic diseases. We performed univariate and multivariate analyses of serological indices and their correlations with RBP and performed receiver operating characteristic (ROC) curve analyses of the WNR and GNR. The serum RBP level decreased markedly in AP compared with that in the acute stage of CP (p < 0.05). The GGT, alkaline phosphatase (ALP), total protein (TP), albumin (ALB), prealbumin (PA), 5'-nucleotide, and uric acid (UC) serum levels were significantly higher for fibrotic CP than for the acute stage of CP without fibrosis (p < 0.05). With progressing to pancreatic fibrosis, the liver injury-related indicators, prothrombin time (PT), activated partial thromboplastin time (APTT), D-Dimer, aspartate aminotransferase (AST), and GGT, gradually increased (p < 0.05). ROC curve analysis suggests that both the WNR (area under the curve [AUC] = 0.821) and GNR (AUC = 0.778) can be used to differentiate pancreatitis types.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtm.2020.05.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7287189PMC
September 2020

A hierarchical data reconciliation based on multiple time-delay interval estimation for industrial processes.

ISA Trans 2020 Oct 4;105:198-209. Epub 2020 Jun 4.

School of Automation, Central South University, Changsha 410083, PR China.

With the increasing demand for energy conversation and high efficiency, data quality is of great important to the operation management and monitoring in industrial applications. Data reconciliation, as a data processing technology, provides great potential to improve quality of process data, and is widely used to reduce measurement error and estimate unmeasured parameters. However, there are reactors connected in series in the long-running industrial processes so that liquid material information is difficult to mark and trace, and the liquid material has different residence times in each reactor due to the differences in the internal structure and operation mode. The time-delay in different reactors may be various and time-varying. In this paper, to solve these problems, a multiple time-delay interval estimation based hierarchical data reconciliation method is put forward. First, the multiple time-delay interval estimation is developed according to the process mechanism analysis and modeling. Then, an improved discrete state transition solution approach is presented to solve the data time-matching with multiple time-delay interval estimation for different reactors. Finally, a hierarchical data reconciliation frame is built by data characteristics. The feasible of the proposed data reconciliation method is verified utilizing the industrial application results.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.isatra.2020.06.001DOI Listing
October 2020

The lncRNA RUNX1-IT1 regulates C-FOS transcription by interacting with RUNX1 in the process of pancreatic cancer proliferation, migration and invasion.

Cell Death Dis 2020 06 2;11(6):412. Epub 2020 Jun 2.

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, P. R. China.

Numerous long noncoding RNAs (lncRNAs) are aberrantly expressed in pancreatic cancer (PC); however, their functions and mechanisms in cancer progression are largely unknown. In this study, we identified a novel PC-associated lncRNA, RUNX1-IT1, that was significantly upregulated in PC patient samples from multiple centers and associated with poor prognosis. In vitro and in vivo, alterations in RUNX1-IT1 expression markedly affected PC proliferation, migration and invasion. RUNX1-IT1 contributed to the progression of PC by interacting with the adjacent gene RUNX1. Rescue experiments showed that RUNX1 reduced the cancer-promoting effect of RUNX1-IT1. RNA-seq analysis after silencing RUNX1-IT1 and RUNX1 highlighted alterations in the common target C-FOS. Mechanistically, we demonstrated that RUNX1-IT1 was a trans-acting factor that participated in the proliferation, migration and invasion of PC by recruiting RUNX1 to the C-FOS gene promoter. Furthermore, RUNX1-IT1 enhanced the transcription of the RUNX1 gene, indicating its potential as a cis-regulatory RNA involved in the upstream regulation of RUNX1. Overall, RUNX1-IT1 is a crucial oncogenic lncRNA that activates C-FOS expression by regulating and recruiting RUNX1 and is a potential prognostic biomarker and therapeutic target for PC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2617-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7265432PMC
June 2020

Activating miRNA-mRNA network in gemcitabine-resistant pancreatic cancer cell associates with alteration of memory CD4 T cells.

Ann Transl Med 2020 Mar;8(6):279

Institute of Hepatopancreatobiliary Surgery, Chongqing General Hospital, University of Chinese Academy of Sciences, Chongqing 400038, China.

Background: To identify key microRNAs (miRNAs) and their target mRNAs related to gemcitabine-resistant pancreatic cancer (PC) and investigate the association between gemcitabine-resistant-related miRNAs and mRNAs and immune infiltration.

Methods: Expression profiles of miRNAs and mRNAs were obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed miRNAs and mRNAs (referred to as "DEmiRNAs" and "DEmRNAs", respectively) were distinguished between gemcitabine-resistant PC cells and its parental cells. The DEmRNAs targeted by the DEmiRNAs were retrieved using miRDB, microT, and Targetscan. Furthermore, GO and KEGG pathway enrichment analysis and GSEA were performed. The Kaplan-Meier plotter was used to analyze the prognosis of key DEmiRNAs and DEmRNAs on PC patients. The relationship between the key DEmRNAs and tumor-infiltrating immune cells in PC was investigated using CIBERSORT method using the LM22 signature as reference. Key infiltrating immune cells were further analyzed for the associations with prognosis of TCGA PAAD patients.

Results: Four DEmiRNAs, including hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p, and hsa-miR-584-5p, were identified to target seven DEmRNAs, including MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6, individually, in gemcitabine-resistant PC cells versus parental cells. Gemcitabine-resistant PC cells were enriched in proteasome-related, immune-related, and memory CD4 T cell-related pathways, indicating a gemcitabine therapeutic effect on PC cells. All four DEmiRNAs and almost all DEmRNAs had an impact on the prognosis of PC patients. All seven DEmRNAs had remarkable effects on CD4 memory T cells, which were affected by the gemcitabine therapeutic effect. Effector memory CD4 T cells rather than central memory CD4 T cells predicted a good prognosis according to the TCGA PAAD dataset.

Conclusions: Gemcitabine resistance can alter the fraction of memory CD4 T cells via hsa-miR-3178, hsa-miR-485-3p, hsa-miR-574-5p and hsa-miR-584-5p targeted MSI2, TEAD1, GNPDA1, RND3, PRKACB, TRIM68, and YKT6 network in PC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21037/atm.2020.03.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7186712PMC
March 2020

Magnesium oxide anchored into a hollow carbon sphere realizes synergistic adsorption and activation of CO for electrochemical reduction.

Chem Commun (Camb) 2020 Jun 29;56(45):6062-6065. Epub 2020 Apr 29.

State Key Lab of Organic-Inorganic Composites, Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P. R. China.

We report the synergistic adsorption and activation of CO by using magnesium oxide anchored into a hollow carbon sphere (MgO/HCS) as an efficient catalyst for electrochemical reduction of CO (ERC). The MgO/HCS catalyst exhibits a high selectivity for CO production with a faradaic efficiency of 81.7% at -1.0 V vs. RHE and a partial current density (PCD) of 16.7 mA cm in aqueous electrolyte.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc00929fDOI Listing
June 2020

Metabolomics identified new biomarkers for the precise diagnosis of pancreatic cancer and associated tissue metastasis.

Pharmacol Res 2020 06 8;156:104805. Epub 2020 Apr 8.

Key Laboratory of Systems Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, 200240, China; Laboratory for Functional Metabolomics Science, Shanghai Jiao Tong University, Shanghai, 200240, China. Electronic address:

Pancreatic cancer (PC) is one of the most aggressive malignancies with high mortality due to a complex and latent pathogenesis leading to the severe lack of early diagnosis methods. To improve clinical diagnosis and enhance therapeutic outcome, we employed the newly developed precision-targeted metabolomics method to identify and validate metabolite biomarkers from the plasma samples of patients with pancreatic cancer that can sensitively and efficiently diagnose the onsite progression of the disease. Many differential metabolites have the capacity to markedly distinguish patients with pancreatic cancer (n = 60) from healthy controls (n = 60). To further enhance the specificity and selectivity of metabolite biomarkers, a dozen tumor tissues from PC patients and paired normal tissues were used to clinically validate the biomarker performance. We eventually verified five new metabolite biomarkers in plasma (creatine, inosine, beta-sitosterol, sphinganine and glycocholic acid), which can be used to readily diagnose pancreatic cancer in a clinical setting. Excitingly, we proposed a panel biomarker by integrating these five individual metabolites into one pattern, demonstrating much higher accuracy and specificity to precisely diagnose pancreatic cancer than conventional biomarkers (CA125, CA19-9, CA242 and CEA); moreover, this plasma panel biomarker used for PC diagnosis is also quite convenient to implement in clinical practice. Using the same metabolomics method, we characterized succinic acid and gluconic acid as having a great capability to monitor the progression and metastasis of pancreatic cancer at different stages. Taken together, this metabolomics method was used to identify and validate metabolite biomarkers that can precisely and sensitively diagnose the onsite progression and metastasis of pancreatic cancer in a clinical setting. Furthermore, such effort should leave clinicians with the correct time frame to facilitate early and efficient therapeutic interventions, which could largely improve the five-year survival rate of PC patients by significantly lowering clinical mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.phrs.2020.104805DOI Listing
June 2020

Deep-Learning-Based Probabilistic Forecasting of Electric Vehicle Charging Load With a Novel Queuing Model.

IEEE Trans Cybern 2021 Jun 18;51(6):3157-3170. Epub 2021 May 18.

With the emerging electric vehicle (EV) and fast charging technologies, EV load forecasting has become a concern for planners and operators of EV charging stations (CSs). Due to the nonstationary feature of the traffic flow (TF) and the erratic nature of the charging procedures, EV charging load is difficult to accurately forecast. In this article, TF is first predicted using a deep-learning-based convolutional neural network (CNN), and different forecast uncertainties are evaluated to formulate the TF prediction intervals (PIs). Then, the EV arrival rates are calculated according to the historical data and the proposed mixture model. Based on TF forecasting and arrival rate results, the EV charging process is studied to convert the TF to the charging load using a novel probabilistic queuing model that takes into consideration charging service limitations and driver behaviors. The proposed models are assessed using the actual TF data, and the results show that the uncertainties of the EV charging load can be learned comprehensively, indicating significant potential for practical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1109/TCYB.2020.2975134DOI Listing
June 2021

Fluorine Doped Cagelike Carbon Electrocatalyst: An Insight into the Structure-Enhanced CO Selectivity for CO Reduction at High Overpotential.

ACS Nano 2020 Feb 14;14(2):2014-2023. Epub 2020 Feb 14.

State Key Lab of Organic-Inorganic Composites, Beijing Advanced Innovation Center for Soft Matter Science and Engineering , Beijing University of Chemical Technology , Beijing , 100029 , People's Republic of China.

The critical bottleneck of electrocatalytic CO reduction reaction (CORR) lies in its low efficiency at high overpotential caused by competitive hydrogen evolution. It is challenging to develop an efficient catalyst achieving both high current density and high Faradaic efficiency (FE) for CORR. Herein, we synthesized fluorine-doped cagelike porous carbon (F-CPC) by purposely tailoring its structural properties. The optimized F-CPC possesses large surface area with moderate mesopore and abundant micropores as well as high electrical conductivity. When used as catalyst for CORR, F-CPC exhibits FE of 88.3% for CO at -1.0 V RHE with a current density of 37.5 mA·cm . Experimental results and finite element simulations demonstrate that the excellent CORR performance of F-CPC at high overpotential should be attributed to its structure-enhanced electrocatalytic process stemming from its cagelike morphology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acsnano.9b08528DOI Listing
February 2020

MiR-24-3p Inhibits the Progression of Pancreatic Ductal Adenocarcinoma Through LAMB3 Downregulation.

Front Oncol 2019 21;9:1499. Epub 2020 Jan 21.

Department of First Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, China.

Pancreatic ductal adenocarcinoma (PDAC) is associated with several genetic syndromes. However, the molecular mechanism underlying PDAC progression is still unknown. In this study, we showed that Laminin Subunit Beta 3 (LAMB3) was aberrantly overexpressed in PDAC and was closely associated with the overall survival rate of patients with PDAC. Functional studies demonstrated that LAMB3 played important roles in cell proliferation, the cell cycle, and invasion capacity. Using bioinformatics analysis, we determined that miR-24-3p was an upstream miRNA of LAMB3, and further experiments verified that miR-24-3p regulated LAMB3 expression in PDAC cells. A dual-luciferase reporter system demonstrated that miR-24-3p directly targeted the LAMB3 3'UTR, and FISH assay confirmed that miR-24-3p and LAMB3 mRNA mostly resided in cytoplasm, accounting for their post-translational regulation. Rescue assay demonstrated that miR-24-3p exerted its anti-cancer role by suppressing LAMB3 expression. Finally, by using a subcutaneous xenotransplanted tumor model, we demonstrated that miR-24-3p overexpression inhibited the proliferation of PDAC by suppressing LAMB3 expression . Collectively, our results provide evidence that the miR-24-3p/LAMB3 axis plays a vital role in the progression of PDAC and indicate that the miR-24-3p/LAMB3 axis may represent a novel therapeutic target for PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fonc.2019.01499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6985431PMC
January 2020

Functional Significance and Therapeutic Potential of miR-15a Mimic in Pancreatic Ductal Adenocarcinoma.

Mol Ther Nucleic Acids 2020 Mar 20;19:228-239. Epub 2019 Nov 20.

Department of Pathology, Renaissance School of Medicine, Stony Brook University, Stony Brook, NY 11794, USA. Electronic address:

Treatment of pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. There is an urgent need to develop novel strategies to enhance survival and improve patient prognosis. MicroRNAs (miRNAs) play critical roles as oncogenes or tumor suppressors in the regulation of cancer development and progression. In this study, we demonstrate that low expression of miR-15a is associated with poor prognosis of PDAC patients. miR-15a expression is reduced in PDAC while closely related miR-16 expression remains relatively unchanged. miR-15a suppresses several important targets such as Wee1, Chk1, Yap-1, and BMI-1, causing cell cycle arrest and inhibiting cell proliferation. Ectopic expression of miR-15a sensitizes PDAC cells to gemcitabine reducing the half maximal inhibitory concentration (IC) more than 6.5-fold. To investigate the therapeutic potential of miR-15a, we used a modified miR-15a (5-FU-miR-15a) with uracil (U) residues in the guide strand replaced with 5-fluorouracil (5-FU). We demonstrated enhanced inhibition of PDAC cell proliferation by 5-FU-miR-15a compared to native miR-15a. In vivo we showed the therapeutic power of 5-FU-miR-15a alone or in combination with gemcitabine with near complete elimination of PDAC lung metastatic tumor growth. These results support the future development of 5-FU-miR-15a as a novel therapeutic agent as well as a prognostic biomarker in the clinical management of PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.omtn.2019.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921186PMC
March 2020

Prediction of hydrological responses to land use change.

Sci Total Environ 2020 Mar 16;708:134998. Epub 2019 Nov 16.

Shanghai Municipal Engineering Design Institute Design Institute 6 Co., Ltd., Anhui Province, China.

The change of land use and land coverage (LULC) has a direct impact on the underlying surface of the drainage basin, hence alters the rainfall-runoff processes. This study described the procedure to use the CA-Markov model to predict the future distributed land use in the Qinhuai River basin in 2028 based on the historical evolution. The hydrological model HEC-HMS was then utilized to examine the impact of land use change on the hydrological responses of the drainage basin. The major findings were as follows: (1) from 2001 to 2010, major changes detected in land use were substantial conversion of paddy fields, forest land and dryland into urban land (increased by 56.81%), following the trend recognized by CA-Markov model, urban land and dry land were predicted to increase by 17.47% and 14.05% by 2028. (2) the projected land use in 2028 resulted in various degrees of increase in flood peak and volume according to the severity of the floods characterized by flood volumes, the smaller floods were predicted to result in more significant increase with 3.5% increase in flood peak and 2.9% increase in flood volume while these values decreased to 0.4% and 1.1% for a big scale flood; (3) greater increase in urbanization leads to greater change of the flood peak and volume change. For small scale floods, when the proportion of urban land use increases by 30% to 60% hypothetically, the relative increment in flood peaks increase from 4.7% to 8.1% with 4% to 6.6% increase in the flood volume; (4) on the sub-basin scale, the trend of change in urban land use and the flood peak and volume were consistent. The methods and conclusions may shed light on urban land development and management and design of flood control measures in a large river basin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2019.134998DOI Listing
March 2020

Inhibition of PTP1B blocks pancreatic cancer progression by targeting the PKM2/AMPK/mTOC1 pathway.

Cell Death Dis 2019 11 19;10(12):874. Epub 2019 Nov 19.

State Key Laboratory of Microbial Technology, Shandong University, Jinan, 250100, Shandong, China.

Pancreatic cancer is a highly malignant cancer and lacks effective therapeutic targets. Protein-tyrosine phosphatase 1B (PTP1B), a validated therapeutic target for diabetes and obesity, also plays a critical positive or negative role in tumorigenesis. However, the role of PTP1B in pancreatic cancer remains elusive. Here, we initially demonstrated that PTP1B was highly expressed in pancreatic tumors, and was positively correlated with distant metastasis and tumor staging, and indicated poor survival. Then, inhibition of PTP1B either by shRNA or by a specific small-molecule inhibitor significantly suppressed pancreatic cancer cell growth, migration and colony formation with cell cycle arrest in vitro and inhibited pancreatic cancer progression in vivo. Mechanism studies revealed that PTP1B targeted the PKM2/AMPK/mTOC1 signaling pathway to regulate cell growth. PTP1B inhibition directly increased PKM2 Tyr-105 phosphorylation to further result in significant activation of AMPK, which decreased mTOC1 activity and led to inhibition of p70S6K. Meanwhile, the decreased phosphorylation of PRAS40 caused by decreased PKM2 activity also helped to inhibit mTOC1. Collectively, these findings support the notion of PTP1B as an oncogene and a promising therapeutic target for PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-019-2073-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6864061PMC
November 2019

Silencing ubiquitin-conjugating enzyme 2C inhibits proliferation and epithelial-mesenchymal transition in pancreatic ductal adenocarcinoma.

FEBS J 2019 12 29;286(24):4889-4909. Epub 2019 Nov 29.

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.

Ubiquitin-conjugating enzyme 2C (UBE2C) is a core ubiquitin-conjugating enzyme in the ubiquitin-proteasome system that promotes cell cycle progression. Previous studies have indicated that UBE2C mediates tumorigenesis and progression in various cancers, but its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. This study elucidated the function of UBE2C in PDAC tumorigenesis and progression by determining UBE2C expression via real-time qPCR, western blotting and immunohistochemistry. The associations between UBE2C expression and clinicopathological characteristics and survival were assessed using a tissue microarray based on a multicentre PDAC cohort. We found that UBE2C was strongly expressed in PDAC patient tissues and was negatively associated with clinical stage, lymph node metastasis, perineural invasion and survival (all P < 0.05). Multivariate analysis revealed that high UBE2C expression is an independent risk factor for PDAC (P = 0.001). In the PDAC cell lines CFPAC-1 and Panc-1, silencing UBE2C suppressed cell proliferation by inducing G1/S arrest mediated by downregulation of cyclin D1. Furthermore, UBE2C knockdown decreased the migration of PDAC cells in vitro by downregulating epithelial-mesenchymal transition (EMT). RNA-seq analysis showed that upon silencing UBE2C in CFPAC-1 cells, cyclin D1 and vimentin were downregulated by approximately 3.5-fold and 2.6-fold, respectively, and the major enriched pathways were related to cell cycle progression. Experiments on tumour-bearing mice injected with CFPAC-1 cells indicated that UBE2C depletion significantly inhibits tumour growth in vivo. These results suggest that UBE2C is involved in the development and progression of PDAC by regulating cell proliferation and EMT. UBE2C is a novel potential therapeutic target for pancreatic cancer. DATABASE: Data are available in the GEO database under accession number GSE137172.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/febs.15134DOI Listing
December 2019

Association of radiomic imaging features and gene expression profile as prognostic factors in pancreatic ductal adenocarcinoma.

Am J Transl Res 2019 15;11(7):4491-4499. Epub 2019 Jul 15.

Department of Radiology, Southwest Hospital, Third Military Medical University Chongqing, China.

In this study, we investigated whether radiomic features of CT image data can accurately predict HMGA2 and C-MYC gene expression status and identify the patient survival time using a machine learning approach in pancreatic ductal adenocarcinoma (PDAC). A cohort of 111 patients with PDAC was enrolled in our study. Radiomic features were extracted using conventional (shape and texture analysis) and deep learning approaches following to segmentation of preoperative CT data. To predict patient survival time, significant radiomic features were identified using a log-rank test. After surgical resection, level of HMGA2 and C-MYC gene expressions of PDAC tumor regions were classified using a support vector machines method. The model was evaluated in terms of accuracy, sensitivity, specificity, and area under the curve (AUC). Besides, inter-reader reliability analysis was used to demonstrate the robustness of the proposed features. The identified features consistently achieved good performance in survival prediction and classification of gene expression status, on images segmented by different radiologists. Using CT data from 111 patients, six features in the segmented region of images were highly correlated with survival time. Using extracted deep features of excised lesions from 47 patients, we observed an average AUC score of 0.90 with an accuracy of 95% in C-MYC prediction (sensitivity: 92% and specificity: 98%). In HGMA2 group, using shape features, the average AUC score was measured as 0.91 with an accuracy of 88% (sensitivity: 89% and specificity: 88%). In conclusion, the radiomic features of CT image can accurately predict the expression status of HMGA2 and C-MYC genes and identify the survival time of PDAC patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6684898PMC
July 2019

miR-23a-5p inhibits cell proliferation and invasion in pancreatic ductal adenocarcinoma by suppressing ECM1 expression.

Am J Transl Res 2019 15;11(5):2983-2994. Epub 2019 May 15.

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Army Medical University Chongqing 400038, China.

Pancreatic ductal adenocarcinoma (PDAC) is a genetic disease and a leading cause of cancer-related mortality. However, the molecular mechanism underlying PDAC progression remains unclear. In this study, we first confirmed that ECM1 is significantly upregulated in PDAC tissues and that its high levels of expression are closely associated with an advanced histologic grade and a poor prognosis using The Cancer Genome Atlas (TCGA) dataset and the Gene Expression Omnibus (GEO) database. We then found that miR-23a-5p binds directly to the ECM1 3'-untranslated region (3'-UTR), thereby inhibiting ECM1 expression. Functional studies revealed that the induced expression of ECM1 promoted oncogenic abilities and reversed the suppressive effects induced by miR-23a-5p. Collectively, our findings indicate that ECM1 is a proto-oncogene and show that targeting the miR-23a-5p/ECM1 axis may represent a promising therapeutic strategy for PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556669PMC
May 2019

Prognostic Values of CD38CD101PD1CD8 T Cells in Pancreatic Cancer.

Immunol Invest 2019 Jul 28;48(5):466-479. Epub 2019 Jan 28.

a Department of Pathophysiology , Third Military Medical University , Chongqing , PR China.

Programmed death-1 (PD-1), a key immune checkpoint molecule, has been developed as an oncotherapy target for various carcinomas. However, treatment with anti-PD-1 elicited only a minimal effect in pancreatic ductal adenocarcinoma (PDAC). Subsequent studies revealed the existence of a subset of PD-1 T cells coexpressing CD38 and CD101, representing a fixed dysfunctional subpopulation that are not able to be rescued by anti-PD-1 immunotherapy. However, whether this subpopulation of PD-1 expressing CD8 T cells could be useful in predicting PDAC stage or prognosing survival is unknown. In this study, we used flow cytometry and immunofluorescence assay to analyze the expression of CD38 and CD101 in 183 clinical PDAC samples, including 84 of peripheral blood and 99 of surgical tissues. High coexpression of CD38/CD101 on peripheral PD-1CD8 T cells or tumor-infiltrating lymphocytes (TILs) was found to be most significantly correlated with Tumor/Node/Metastasis (T/N/M) classification and clinical stage, in contrast PD-1CD8 T cells could not correlate with T classification. CD38/CD101 co-repression on TILs also correlated with the poor survival in these PDAC patient samples. Our data suggest that CD38/CD101 might represent a more helpful biomarker than PD-1 alone for diagnosis and prognosis of PDAC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/08820139.2019.1566356DOI Listing
July 2019

Doublecortin-Like Kinase 1 (DCLK1) Regulates B Cell-Specific Moloney Murine Leukemia Virus Insertion Site 1 (Bmi-1) and is Associated with Metastasis and Prognosis in Pancreatic Cancer.

Cell Physiol Biochem 2018 19;51(1):262-277. Epub 2018 Nov 19.

Institute of Hepatopancreatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing,

Background/aims: Cancer stem cells (CSCs) are largely responsible for tumor relapse and metastatic behavior. Doublecortin-like kinase 1 (DCLK1) was recently reported to be a biomarker for gastrointestinal CSCs and involved in the epithelial-mesenchymal transition (EMT) and tumor progression. B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is a crucial regulator of CSC self-renewal, malignant transformation and EMT, and a previous study from our group showed that Bmi-1 is upregulated in pancreatic cancer progression and participates in EMT. However, it remains unclear whether DCLK1 is involved in pancreatic cancer or whether DCLK1 is associated with the altered level of Bmi-1 expression.

Methods: The correlation of DCLK1 expression and clinical features of pancreatic cancer was analyzed in 210 paraffin-embedded archived pancreatic cancer specimens by immunohistochemical analysis. The biological effects of DCLK1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays, cell migration by wound healing assay and cell invasion by Transwell invasion assay. We further investigated the effect of therapeutic siRNA targeting DCLK1 on pancreatic cancer cell growth in vivo. Moreover, the molecular mechanism by which DCLK1 upregulates Bmi-1 expression was explored using real-time PCR, western blotting and Co-immunoprecipitation assay.

Results: DCLK1 is overexpressed in pancreatic cancer and is related to metastasis and prognosis. Knockdown of DCLK1 markedly suppressed cell growth in vitro and in vivo and also inhibited the migration and invasion of pancreatic cancer cells. Furthermore, we found that DCLK1 silencing could inhibit EMT in cancer cells via downregulation of Bmi-1 and the mesenchymal markers Snail and Vimentin and upregulation of the epithelial marker E-cadherin. Moreover, high DCLK1 expression in human pancreatic cancer samples was associated with a mesenchymal phenotype and increased cell proliferation. Further co-immunoprecipitation indicated that DCLK1 did not interact with Bmi-1 directly.

Conclusion: Our data suggest that upregulation of DCLK1 may contribute to pancreatic cancer metastasis and poor prognosis by increasing Bmi-1 expression indirectly. The findings indicate that inhibiting DCLK1 expression might be a novel strategy for pancreatic cancer therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000495228DOI Listing
December 2018

Retraction notice to "Silencing circular RNA hsa_circ_0000977 suppresses pancreatic ductal adenocarcinoma progression by stimulating miR-874-3p and inhibiting PLK1 expression" [Cancer Letters 422C (2018) 70-80].

Cancer Lett 2018 12;438:232

Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Southern Medical University, Industrial Road No.253, Guangzhou, Guangdong510280, China.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.canlet.2018.09.027DOI Listing
December 2018
-->