ABSTRACT
Cervical cancer (CC) is the second most common malignancy in women worldwide. The mechanism underlying CC development remains unclear. Recently, Circular RNAs (circRNAs)have attracted attention because of its role in tumorigenesis. To investigate circRNAsin CC, RNA sequencing was employed to characterize circRNA expression profile between CC tissues and matched adjacent normal tissues. The expression of hsa_circ_0003204 was examined in CC tissues and cell lines by real-time PCR. Migration assay and invasion assay were used to verify the effect of hsa_circ_0003204 on migration and invasion ability in CC cell lines. Tumor formation assay in nude mice was used to analyze the effect of hsa_circ_0003204 on the tumorigenicity of CC cell lines in vitro. Western blotting analyzes were performed to investigate the role of hsa_circ_0003204 in the regulation of MAPK signaling activation. We found that circRNA hsa_circ_0003204 was significantly upregulated in CC tissues. The function and potential molecular mechanisms of hsa_circ_0003204 were also investigated in vitro and in vivo. Hsa_circ_0003204 knockdown reduced cell growth, migration, and invasion but promoted cells apoptosis. However, the over-expression of hsa_circ_0003204 had the opposite effect. The MAPK pathway was different in hsa_circ_0003204 over-expression or down-expression cells, compared to parental cells. In addition, over-expression of hsa_circ_0003204 significantly increased tumor volume and tumor weight in vivo.Taken together, results indicated hsa_circ_0003204 may serve as a potential therapeutic target for patients with CC.
Subject(s)
MAP Kinase Signaling System , Mitogen-Activated Protein Kinase Kinases/metabolism , RNA, Circular/genetics , RNA, Circular/metabolism , Uterine Cervical Neoplasms/metabolism , Cell Movement , Cell Proliferation , Female , Humans , Neoplasm Invasiveness , Uterine Cervical Neoplasms/genetics , Uterine Cervical Neoplasms/pathologyABSTRACT
An amendment to this paper has been published and can be accessed via the original article.
ABSTRACT
BACKGROUND: miRNA expression profiles in ectopic endometrium (EC) serving as pathophysiologic genetic fingerprints contribute to determining endometriosis progression; however, the underlying molecular mechanisms remain unknown. METHODS: miRNA microarray analysis was used to determine the expression profiling of EC fresh tissues. qRT-PCR was performed to screen miR-205-5p expression in EC tissues. The roles of miR-205-5p and its candidate target gene, angiopoietin-2 (ANGPT2), in endometriosis progression were confirmed on the basis of both in vitro and in vivo systems. miR-205-5p and ANGPT2 expression were measured by in situ hybridization and immunochemistry, and their clinical significance was statistically analysed. RESULTS: miR-205-5p was screened as a novel suppressor of endometriosis through primary ectopic endometrial stromal cell migration, invasion, and apoptosis assay in vitro, along with endometrial-like xenograft growth and apoptosis in vivo. In addition, ANGPT2 was identified as a direct target of miR-205-5p through bioinformatic target prediction and luciferase reporter assay. Re-expression and knockdown of ANGPT2 could respectively rescue and simulate the effects induced by miR-205-5p. Importantly, the miR-205-5p-ANGPT2 axis was found to activate the ERK/AKT pathway in endometriosis. Finally, miR-205-5p and ANGPT2 expression were closely correlated with the endometriosis severity. CONCLUSION: The newly identified miR-205-5p-ANGPT2-AKT/ERK axis illustrates the molecular mechanism of endometriosis progression and may represent a novel diagnostic biomarker and therapeutic target for disease treatment.
Subject(s)
Angiopoietin-2/genetics , Endometriosis/metabolism , Endometrium/cytology , Mesenchymal Stem Cells/metabolism , MicroRNAs/metabolism , Angiopoietin-2/metabolism , Animals , Apoptosis , Cells, Cultured , Endometriosis/pathology , Endometrium/pathology , Female , Humans , Mice , Mice, Nude , MicroRNAs/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Proto-Oncogene Proteins c-akt/metabolismABSTRACT
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer mortality. Chemotherapy resistance remains a major challenge for treating advanced CRC. Therefore, the identification of targets that induce drug resistance is a priority for the development of novel agents to overcome resistance. Dragon (also known as RGMb) is a member of the repulsive guidance molecule (RGM) family. We previously showed that Dragon expression increases with CRC progression in human patients. In the present study, we found that Dragon inhibited apoptosis and increased viability of CMT93 and HCT116 cells in the presence of oxaliplatin. Dragon induced resistance of xenograft tumor to oxaliplatinin treatment in mice. Mechanistically, Dragon inhibited oxaliplatin-induced JNK and p38 MAPK activation, and caspase-3 and PARP cleavages. Our results indicate that Dragon may be a novel target that induces drug resistance in CRC.
Subject(s)
Cell Adhesion Molecules, Neuronal/biosynthesis , Colonic Neoplasms/drug therapy , Colonic Neoplasms/metabolism , Nerve Tissue Proteins/biosynthesis , Neural Cell Adhesion Molecules/biosynthesis , Organoplatinum Compounds/pharmacology , Animals , Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm , HCT116 Cells , Humans , Mice , Mice, Inbred C57BL , Oxaliplatin , Xenograft Model Antitumor AssaysABSTRACT
Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and a major cause of cancer death. However, the molecular mechanisms underlying CRC initiation, growth and metastasis are poorly understood. Dragon (RGMb), a member of the repulsive guidance molecule (RGM) family, has been recently identified as a co-receptor for bone morphogenetic protein (BMP) signaling, but the role of Dragon in CRC development is undefined. Here, we show that Dragon expression was increased in colon cancer tissues compared to control tissues in CAC mouse model and in human patients. Dragon promoted proliferation of CT26.WT and CMT93 colon cancer cells and accelerated tumor growth in the xenograft mouse model. Dragon's action on colon cancer development was mediated via the BMP4-Smad1/5/8 and Erk1/2 pathways. Therefore, our results have revealed that Dragon is a novel gene that promotes CRC growth through the BMP pathway. Dragon may be exploited as a potential therapeutic target for CRC treatment.
Subject(s)
Cell Adhesion Molecules, Neuronal/genetics , Colorectal Neoplasms/genetics , Colorectal Neoplasms/pathology , Nerve Tissue Proteins/genetics , Animals , Cell Adhesion Molecules, Neuronal/biosynthesis , Cell Proliferation/genetics , Colorectal Neoplasms/metabolism , GPI-Linked Proteins , Gene Knockdown Techniques , Humans , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Nerve Tissue Proteins/biosynthesis , Signal Transduction , Xenograft Model Antitumor AssaysABSTRACT
Trefoil factor 1 (TFF1), a member of the trefoil peptide family, is not only associated with mucosal protection and restoration but is also correlated with tumorigenesis of the gastrointestinal tract. In an early study, we performed sequence analysis and identified one potential miR423-5p binding site within the 3'-untranslated region of TFF1 using microRNA target prediction tools. In the current study, we demonstrated that the coding DNA region within TFF1 is also a candidate for miR218-5p targeting. We used real-time PCR and in situ hybridization to analyze the correlation between miR218-5p and TFF1 expression in tumor lesions and paracancerous tissue in gastric cancer (GC) samples. Additionally, endogenous and exogenous TFF1 were suppressed by miR218-5p in gastric cancer cells and influenced the progression of GC in an Erk1/2-dependent manner. Targeting miR218-5p may provide a novel strategy for the treatment of GC.
Subject(s)
Cell Proliferation/genetics , MicroRNAs/genetics , Mitogen-Activated Protein Kinase 1/metabolism , Mitogen-Activated Protein Kinase 3/metabolism , Stomach Neoplasms/genetics , Tumor Suppressor Proteins/genetics , Animals , Base Sequence , Blotting, Western , Cell Line, Tumor , Gene Expression Regulation, Neoplastic , Humans , In Situ Hybridization , Mice, Nude , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic Acid , Stomach Neoplasms/metabolism , Stomach Neoplasms/pathology , Transplantation, Heterologous , Trefoil Factor-1 , Tumor Burden/genetics , Tumor Suppressor Proteins/metabolismABSTRACT
In this study, we developed an integrated hospital-associated urinary tract infection (HAUTI) surveillance information system (called iHAUTISIS) based on existing electronic medical records (EMR) systems for improving the work efficiency of infection control professionals (ICPs) in a 730-bed, tertiary-care teaching hospital in Taiwan. The iHAUTISIS can automatically collect data relevant to HAUTI surveillance from the different EMR systems, and provides a visualization dashboard that helps ICPs make better surveillance plans and facilitates their surveillance work. In order to measure the system performance, we also created a generic model for comparing the ICPs' work efficiency when using existing electronic culture-based surveillance information system (eCBSIS) and iHAUTISIS, respectively. This model can demonstrate a patient's state (unsuspected, suspected, and confirmed) and corresponding time spent on surveillance tasks performed by ICPs for the patient in that state. The study results showed that the iHAUTISIS performed better than the eCBSIS in terms of ICPs' time cost. It reduced the time by 73.27 s, when using iHAUTISIS (114.26 s) and eCBSIS (187.53 s), for each patient on average. With increased adoption of EMR systems, the development of the integrated HAI surveillance information systems would be more and more cost-effective. Moreover, the iHAUTISIS adopted web-based technology that enables ICPs to online access patient's surveillance information using laptops or mobile devices. Therefore, our system can further facilitate the HAI surveillance and reduce ICPs' surveillance workloads.
Subject(s)
Cross Infection/diagnosis , Data Mining/methods , Efficiency, Organizational/statistics & numerical data , Electronic Health Records/organization & administration , Sentinel Surveillance , Urinary Tract Infections/diagnosis , Workflow , Cross Infection/epidemiology , Humans , Systems Integration , Taiwan/epidemiology , Urinary Tract Infections/epidemiology , User-Computer Interface , Workload/statistics & numerical dataABSTRACT
A novel tuberculosis (TB) gene vaccine containing mouse granulocyte macrophage-colony stimulating factor (mGM-CSF) and a TB antigen (Ag85A) was developed in this study. The genes encoding Ag85A and mGM-CSF were amplified by PCR respectively from the Ag85A-containing pBSby5 and pC-mGM-CSF. The genes were then cloned into two different polylinker sites of plasmid pIRES, forming a novel TB gene vaccine construct pI85AGM. Following transfection of pI85AGM plasmid into 7721 cell line by Lipofectamine(TM), the expression of Ag85A and GM-CSF proteins was identified by Western blotting or RT-PCR. Then Balb/c mice were inoculated with the recombinant pI85AGM, pI85A, pIGM or plasmid alone, respectively. The activities of CTL, NK cells and the Ag85A-stimulated proliferation of spleen cells were measured by MTT method. The serum antibody against Ag85A was detected by ELISA. The results showed that the Ag85A and GM-CSF proteins could be expressed in 7721 cell line and the activity of CTLs and the proliferation of spleen cells were significantly increased in the pI85AGM-immunized mice, indicating that the pI85AGM-immunized mice could generate specific immune responses to Ag85A. This study might provide possibility for developing novel anti-TB gene vaccine.
Subject(s)
Tuberculosis Vaccines/genetics , Tuberculosis Vaccines/immunology , Acyltransferases/genetics , Acyltransferases/immunology , Acyltransferases/metabolism , Animals , Antibodies, Bacterial/blood , Antibodies, Bacterial/immunology , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Antigens, Bacterial/metabolism , Blotting, Western , Cell Line, Tumor , Cell Proliferation , DNA, Complementary/genetics , Gene Expression , Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Granulocyte-Macrophage Colony-Stimulating Factor/immunology , Granulocyte-Macrophage Colony-Stimulating Factor/metabolism , Humans , Killer Cells, Natural/metabolism , Mice , Mice, Inbred BALB C , Recombinant Proteins/genetics , Recombinant Proteins/immunology , Recombinant Proteins/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Spleen/cytology , Spleen/immunology , T-Lymphocytes, Cytotoxic/immunology , T-Lymphocytes, Cytotoxic/metabolismABSTRACT
With the development of general-purpose processors (GPP) and video signal processing algorithms, it is possible to implement a software-based real-time video encoder on GPP, and its low cost and easy upgrade attract developers' interests to transfer video encoding from specialized hardware to more flexible software. In this paper, the encoding structure is set up first to support complexity scalability; then a lot of high performance algorithms are used on the key time-consuming modules in coding process; finally, at programming level, processor characteristics are considered to improve data access efficiency and processing parallelism. Other programming methods such as lookup table are adopted to reduce the computational complexity. Simulation results showed that these ideas could not only improve the global performance of video coding, but also provide great flexibility in complexity regulation.
