The Role of Long Noncoding RNAs in Gene Expression Regulation

Accumulating evidence highlights that noncoding RNAs, especially the long noncoding RNAs (lncRNAs), are critical regulators of gene expression in development, differentiation, and human diseases, such as cancers and heart diseases. The regulatory mechanisms of lncRNAs have been categorized into four major archetypes: signals, decoys, scaffolds, and guides. Increasing evidence points that lncRNAs are able to regulate almost every cellular process by their binding to proteins, mRNAs, miRNA, and/or DNAs. In this review, we present the recent research advances about the regulatory mechanisms of lncRNA in gene expression at various levels, including pretranscription, transcription regulation, and posttranscription regulation. We also introduce the interaction between lncRNA and DNA, RNA and protein, and the bioinformatics applications on lncRNA research

HSP60, a protein downregulated by IGFBP7 in colorectal carcinoma

<p>Abstract</p> <p>Background</p> <p>In our previous study, it was well defined that <it>IGFBP7 </it>was an important tumor suppressor gene in colorectal cancer (CRC). We aimed to uncover the downstream molecules responsible for <it>IGFBP7</it>'s behaviour in this study.</p> <p>Methods</p> <p>Differentially expressed protein profiles between PcDNA3.1(<it>IGFBP7</it>)-transfected RKO cells and the empty vector transfected controls were generated by two-dimensional gel electrophoresis (2-DE) and mass spectrometry (MS) identification. The selected differentially expressed protein induced by IGFBP7 was confirmed by western blot and ELISA. The biological behaviour of the protein was explored by cell growth assay and colony formation assay.</p> <p>Results</p> <p>Six unique proteins were found differentially expressed in PcDNA3.1(<it>IGFBP7</it>)-transfected RKO cells, including albumin (ALB), 60 kDa heat shock protein(HSP60), Actin cytoplasmic 1 or 2, pyruvate kinase muscle 2(PKM2), beta subunit of phenylalanyl-tRNA synthetase(FARSB) and hypothetical protein. The downregulation of HSP60 by IGFBP7 was confirmed by western blot and ELISA. Recombinant human HSP60 protein could increase the proliferation rate and the colony formation ability of PcDNA3.1(<it>IGFBP7</it>)-RKO cells.</p> <p>Conclusion</p> <p>HSP60 was an important downstream molecule of IGFBP7. The downregulation of HSP60 induced by IGFBP7 may be, at least in part, responsible for IGFBP7's tumor suppressive biological behaviour in CRC.</p

Integrated saccade latency as a measure of fatigue

INTRODUCTION: High workload, long working hours and inadequate sleep patterns can have deleterious effects on an individual’s performance. Fatigue is often linked with compromised cognitive and motor function. Our information processing system becomes overloaded and unable to monitor and suppress irrelevant information. Subsequent changes in oculomotor parameters and cortical processing times may therefore provide useful biomarkers to assess one’s state of fatigue. We propose a new non-invasive method to quantify fatigue by measuring Eye Movement And Intrinsic Latencies (EMAIL) without the use of any eye-tracking equipment. METHODS: The test is easy to perform and employs a Landolt C flanked by ring distractors. The test is presented at an eccentricity of 8°, randomly on either side of fixation point within ±5° elevation. The measurement variable is the time of presentation, δT. The subject’s task is to saccade to the peripheral target, register the orientation of the gap and respond by pressing one of four buttons. The EMAIL test measures the presentation time, δT, the subject needs to detect the peripheral target, generate an appropriate eye-movement and register the orientation of the gap. RESULTS: The EMAIL test was used to measure the stimulus presentation times needed to achieve 73% correct responses (using a one up, two down staircase). These times were subject specific and ranged from 165 to 200ms in the absence of fatigue. We investigated how, δT, is affected by exposure to other visually demanding tasks and levels of controlled fatigue. Measured integrated oculomotor responses such as latencies and visual processing times were found to increase significantly following demanding visual tasks by as much as 20ms, but only when fatigued. Preliminary findings using the EMAIL test also show that this technique can be used to investigate the effect of stimulants such as caffeine and depressants, such as alcohol. CONCLUSIONS: The EMAIL test provides a simple method to measure oculomotor parameters and to investigate how these are affected by fatigue. This method can be incorporated in the overall safety management system that is often needed in a number of work areas that involve visually-demanding and safety-critical tasks. The measured parameters provide information about an individual’s level of alertness and may also be of relevance in other industries in order to evaluate drugs developed to control fatigue

Gland Instance Segmentation by Deep Multichannel Side Supervision

Abstract. In this paper, we propose a new image instance segmentation method that segments individual glands (instances) in colon histology images. This is a task called instance segmentation that has recently become increasingly important. The problem is challenging since not only do the glands need to be segmented from the complex background, they are also required to be individually identified. Here we leverage the idea of image-to-image prediction in recent deep learning by building a framework that automatically exploits and fuses complex multichannel information, regional and boundary patterns, with side supervision (deep supervision on side responses) in gland histology images. Our proposed system, deep multichannel side supervision (DMCS), alleviates heavy feature design due to the use of convolutional neural networks guided by side supervision. Compared to methods reported in the 2015 MICCAI Gland Segmentation Challenge, we observe state-of-the-art results based on a number of evaluation metrics

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指導教員: 西郷, 和

IGFBP-rP1, a potential molecule associated with colon cancer differentiation

<p>Abstract</p> <p>Background</p> <p>In our previous studies, we have demonstrated that insulin-like growth factor binding protein-related protein1 (IGFBP-rP1) played its potential tumor suppressor role in colon cancer cells through apoptosis and senescence induction. In this study, we will further uncover the role of IGFBP-rP1 in colon cancer differentiation and a possible mechanism by revealing responsible genes.</p> <p>Results</p> <p>In normal colon epithelium, immunohistochemistry staining detected a gradient IGFBP-rP1 expression along the axis of the crypt. IGFBP-rP1 strongly expressed in the differentiated cells at the surface of the colon epithelium, while weakly expressed at the crypt base. In colon cancer tissues, the expression of IGFBP-rP1 correlated positively with the differentiation status. IGFBP-rP1 strongly expressed in low grade colorectal carcinoma and weakly expressed in high grade colorectal carcinoma. In vitro, transfection of PcDNA3.1(IGFBP-rP1) into RKO, SW620 and CW2 cells induced a more pronounced anterior-posterior polarity morphology, accompanied by upregulation with alkaline phosphatase (AKP) activity. Upregulation of carcino-embryonic antigen (CEA) was also observed in SW620 and CW2 transfectants. The addition of IGFBP-rP1 protein into the medium could mimic most but not all effects of IGFBP-rP1 cDNA transfection. Seventy-eight reproducibly differentially expressed genes were detected in PcDNA3.1(IGFBP-rP1)-RKO transfectants, using Affymetrix 133 plus 2.0 expression chip platform. Directed Acyclic Graph (DAG) of the enriched GO categories demonstrated that differential expression of the enzyme regulator activity genes together with cytoskeleton and actin binding genes were significant. IGFBP-rP1 could upreguate Transgelin (TAGLN), downregulate SRY (sex determining region Y)-box 9(campomelic dysplasia, autosomal sex-reversal) (SOX9), insulin receptor substrate 1(IRS1), cyclin-dependent kinase inhibitor 2B (p15, inhibits CDK4) (CDKN2B), amphiregulin(schwannoma-derived growth factor) (AREG) and immediate early response 5-like(IER5L) in RKO, SW620 and CW2 colon cancer cells, verified by Real time Reverse Transcription Polymerase Chain Reaction (rtRT-PCR). During sodium butyrate-induced Caco2 cell differentiation, IGFBP-rP1 was upregulated and the expression showed significant correlation with the AKP activity. The downregulation of IRS1 and SOX9 were also induced by sodium butyrate.</p> <p>Conclusion</p> <p>IGFBP-rP1 was a potential key molecule associated with colon cancer differentiation. Downregulation of IRS1 and SOX9 may the possible key downstream genes involved in the process.</p