Molecular BioSystems最新文献

{"title":"MicroRNAs regulate the main events in rice drought stress response by manipulating the water supply to shoots†","authors":"Ehsan Mohseni Fard, Behnam Bakhshi, Mohammad Farsi, Amin Mirshamsi Kakhki, Nava Nikpay, Mohammad Ali Ebrahimi, Mohsen Mardi and Ghasem Hosseini Salekdeh","doi":"10.1039/C7MB00298J","DOIUrl":"https://doi.org/10.1039/C7MB00298J","url":null,"abstract":"<p >MicroRNAs (miRNAs) are small endogenous regulatory RNAs that are involved in a variety of biological processes related to proliferation, development, and response to biotic and abiotic stresses. miRNA profiles of rice (<em>Oryza sativa</em> L. cv. IR64.) leaves in a partial root zone drying (PRD) system were analysed using a high-throughput sequencing approach to identify miRNAs associated with drought signalling. The treatments performed in this study were as follows: well-watered (“wet” roots, WW), wherein both halves of the pot were watered daily; drought (“dry” roots, DD), wherein water was withheld from both halves of the pot; and well-watered/drought (“wet” and “dry” roots, WD), wherein one half of each pot was watered daily, the same as in WW, and water was withheld from the other part, the same as in DD. High-throughput sequencing enabled us to detect novel miRNAs and study the differential expression of known miRNAs. A total of 209 novel miRNAs were detected in this study. Differential miRNA profiling of the DD, WD and WW conditions showed differential expression of 159 miRNAs, among which 83, 44 and 32 miRNAs showed differential expression under both DD and WD conditions. The detection of putative targets of the differentially expressed miRNAs and investigation of their functions showed that most of these genes encode transcription factors involved in growth and development, leaf morphology, regulation of hormonal homeostasis, and stress response. The most important differences between the DD and WD conditions involved regulation of the levels of hormones such as auxin, cytokinin, abscisic acid, and jasmonic acid and also regulation of phosphor homeostasis. Overall, differentially expressed miRNAs under WD conditions were found to differ from those under DD conditions, with such differences playing a role in adaptation and inducing the normal condition. The mechanisms involved in regulating hormonal homeostasis and involved in energy production and consumption were found to be the most important regulatory pathways distinguishing the DD and WD conditions.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 11","pages":" 2289-2302"},"PeriodicalIF":3.743,"publicationDate":"2017-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00298J","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3629040","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"mRNA–miRNA bipartite network reconstruction to predict prognostic module biomarkers in colorectal cancer stage differentiation†","authors":"Habib Motieghader, Morteza Kouhsar, Ali Najafi, Balal Sadeghi and Ali Masoudi-Nejad","doi":"10.1039/C7MB00400A","DOIUrl":"https://doi.org/10.1039/C7MB00400A","url":null,"abstract":"Biomarker detection is one of the most important and challenging problems in cancer studies. Recently, non-coding RNA based biomarkers such as miRNA expression levels have been used for early diagnosis of many cancer types. In this study, a systems biology approach was used to detect novel miRNA based biomarkers for CRC diagnosis in early stages. The mRNA expression data from three CRC stages (Low-grade Intraepithelial Neoplasia (LIN), High-grade Intraepithelial Neoplasia (HIN) and Adenocarcinoma) were used to reconstruct co-expression networks. The networks were clustered to extract co-expression modules and detected low preserved modules among CRC stages. Then, the experimentally validated mRNA-miRNA interaction data were applied to reconstruct three mRNA-miRNA bipartite networks. Twenty miRNAs with the highest degree (hub miRNAs) were selected in each bipartite network to reconstruct three bipartite subnetworks for further analysis. The analysis of these hub miRNAs in the bipartite subnetworks revealed 30 distinct important miRNAs as prognostic markers in CRC stages. There are two novel CRC related miRNAs (hsa-miR-190a-3p and hsa-miR-1277-5p) in these 30 hub miRNAs that have not been previously reported in CRC. Furthermore, a drug-gene interaction network was reconstructed to detect potential candidate drugs for CRC treatment. Our analysis shows that the hub miRNAs in the mRNA-miRNA bipartite network are very essential in CRC progression and should be investigated precisely in future studies. In addition, there are many important target genes in the results that may be critical in CRC progression and can be analyzed as therapeutic targets in future research.","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 2168-2180"},"PeriodicalIF":3.743,"publicationDate":"2017-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00400A","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3791194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A systems biology approach to identify microRNAs contributing to cisplatin resistance in human ovarian cancer cells†","authors":"Weisha Liu, Shuyuan Wang, Shunheng Zhou, Feng Yang, Wei Jiang, Qingyuan Zhang and Lihong Wang","doi":"10.1039/C7MB00362E","DOIUrl":"https://doi.org/10.1039/C7MB00362E","url":null,"abstract":"<p >Cisplatin (CDDP)-based chemotherapy is a standard first-line therapy for ovarian cancer. However, drug resistance remains a major obstacle to its efficacy. Recently, increasing evidence suggested that the aberrant expression of microRNAs (miRNAs) may contribute to drug resistance. Here, we proposed a systems biology analysis strategy to identify the novel miRNAs potentially involved in CDDP resistance in human ovarian cancer cells. Firstly, we identified the candidate miRNAs associated with CDDP resistance using NCI-60 data. Next, the differentially expressed genes (DEGs) in the CDDP-resistant ovarian cancer cell line OVCAR-8R were obtained. After mapping the DEGs to a human protein–protein interaction network, a CDDP resistance-related sub-network for ovarian cancer was constructed, and subsequently the functional gene modules were identified. Then, based on the experimentally validated miRNA regulations to target genes, 4 candidate miRNAs (miR-24-3p, miR-192-5p, miR-139-5p and miR-155-5p) were identified to potentially contribute to ovarian cancer cell chemoresistance to CDDP through mediating OVCAR-8R cell CDDP resistance-related gene modules, which participated in functions that were closely related to “apoptosis”, “cell cycle” and “adhesion”. In addition, we predicted the therapeutic drugs that might reduce or reverse CDDP resistance by targeting these 4 identified miRNAs. This study revealed the underlying mechanism of CDDP resistance, and provided novel potential drug targets and therapeutics for CDDP-resistant ovarian cancer patients.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 11","pages":" 2268-2276"},"PeriodicalIF":3.743,"publicationDate":"2017-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00362E","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3629038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovering potential driver genes through an integrated model of somatic mutation profiles and gene functional information†","authors":"Jianing Xi, Minghui Wang and Ao Li","doi":"10.1039/C7MB00303J","DOIUrl":"https://doi.org/10.1039/C7MB00303J","url":null,"abstract":"<p >The accumulating availability of next-generation sequencing data offers an opportunity to pinpoint driver genes that are causally implicated in oncogenesis through computational models. Despite previous efforts made regarding this challenging problem, there is still room for improvement in the driver gene identification accuracy. In this paper, we propose a novel integrated approach called IntDriver for prioritizing driver genes. Based on a matrix factorization framework, IntDriver can effectively incorporate functional information from both the interaction network and Gene Ontology similarity, and detect driver genes mutated in different sets of patients at the same time. When evaluated through known benchmarking driver genes, the top ranked genes of our result show highly significant enrichment for the known genes. Meanwhile, IntDriver also detects some known driver genes that are not found by the other competing approaches. When measured by precision, recall and F1 score, the performances of our approach are comparable or increased in comparison to the competing approaches.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 2135-2144"},"PeriodicalIF":3.743,"publicationDate":"2017-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00303J","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3791189","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An immunoinformatics approach to promiscuous peptide design for the Plasmodium falciparum erythrocyte membrane protein-1†","authors":"Nazam Khan, Rajender Kumar, Shakti Chauhan and Umar Farooq","doi":"10.1039/C7MB00332C","DOIUrl":"https://doi.org/10.1039/C7MB00332C","url":null,"abstract":"<p > <em>Plasmodium falciparum</em> erythrocyte membrane protein-1 (<em>Pfemp-1</em>), a variant adhesion molecule, can act as a key component of immunity against malaria. In the current selection of malaria vaccines, no efficient vaccines are available that can be employed for its proper treatment. Unfortunately, resistance to post-infection treatments is increasing and therefore there is a pressing need to develop an efficient vaccine. Peptide-based vaccines can be effective tools against malaria but HLA restriction is a major hindrance which can be conquered by using promiscuous peptides. In this work, we employed a combined <em>in silico</em> and experimental approach to identify promiscuous peptides for the treatment of malaria. At first, using the immunoinformatics approach, promiscuous peptides were predicted from two conserved domains, CIDR-1 and DBL-3γ, of the <em>Pfemp-1</em> antigen. These peptides were selected on the basis of their predicted binding affinity with different HLA class-I &amp; class-II alleles. A total of 13 peptides were selected based on their predicted IFN-γ and IL-4 induction ability as well as their hydrophobicity. Out of these 13, the peptide C6 was synthesised and experimentally evaluated for further rationalization, HLA–peptide complex modelling and binding interaction analysis. Interestingly, the peptide C6 (SFIHIYLYRNIRIQL) showed an encouraging immunological response and T-cell proliferation in the immunological assay. This valuable content can aid the better design of more potent and selective vaccine candidates against infectious diseases.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 2160-2167"},"PeriodicalIF":3.743,"publicationDate":"2017-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00332C","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3791193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of phenylalanines outside the dimer interface on phosphotriesterase stability and function†","authors":"Andrew J. Olsen, Leif A. Halvorsen, Ching-Yao Yang, Roni Barak Ventura, Liming Yin, P. Douglas Renfrew, Richard Bonneau and Jin Kim Montclare","doi":"10.1039/C7MB00196G","DOIUrl":"https://doi.org/10.1039/C7MB00196G","url":null,"abstract":"<p >We explore the significance of phenylalanine outside of the phosphotriesterase (PTE) dimer interface through mutagenesis studies and computational modeling. Previous studies have demonstrated that the residue-specific incorporation of <em>para</em>-fluorophenylalanine (<em>p</em>FF) into PTE improves stability, suggesting the importance of phenylalanines in stabilization of the dimer. However, this comes at a cost of decreased solubility due to <em>p</em>FF incorporation into other parts of the protein. Motivated by this, eight single solvent-exposed phenylalanine mutants are evaluated <em>via</em><small>ROSETTA</small> and good correspondence between experiments and these predictions is observed. Three residues, F304, F327, and F335, appear to be important for PTE activity and stability, even though they do not reside in the dimer interface region or active site. While the remaining mutants do not significantly affect structure or activity, one variant, F306L, reveals improved activity at ambient and elevated temperatures. These studies provide further insight into role of these residues on PTE function and stability.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 2092-2106"},"PeriodicalIF":3.743,"publicationDate":"2017-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00196G","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3791345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CXCR7 attenuates the TGF-β-induced endothelial-to-mesenchymal transition and pulmonary fibrosis†","authors":"Shuhong Guan and Jun Zhou","doi":"10.1039/C7MB00247E","DOIUrl":"https://doi.org/10.1039/C7MB00247E","url":null,"abstract":"<p >Lung fibrosis is a progressive and often fatal lung disease characterized by fibroblast proliferation and excessive deposition of extracellular matrix in the lungs. The chemokine receptor CXCR7 has been shown to control cell adhesion, migration and proliferation by regulating the epithelial-to-mesenchymal transition (EMT), but the role of CXCR7 in regulating the endothelial-to-mesenchymal transition (EndMT) and lung fibrosis remains largely unclear. In this study, we investigated the interrelation of CXCR7 and TGF-β, a crucial player in lung fibrogenesis. We report herein that CXCR7 expression is significantly increased in animal models of TGF-β1-induced pulmonary fibrosis and in TGF-β1-treated endothelial cells. TGF-β1 up-regulates CXCR7 expression in a Smad2/3-dependent manner in endothelial cells. The overexpression of CXCR7 effectively attenuates TGF-β1-induced EndMT in lung endothelial cells, whereas CXCR7 knockdown in endothelial cells further promotes TGF-β1-induced EndMT. Mechanically, CXCR7 attenuates EndMT by inhibiting the Jag1–Notch pathway. CXCR7 overexpression in mice also results in a significant enhancement in endothelial markers and a decrease in mesenchymal markers, indicating a decreased susceptibility to TGF-β1-induced lung fibrosis and deposition of extracellular matrix and collagen. These data suggest that CXCR7 upregulation induced by TGF-β is a feedback mechanism to regulate TGF-β-induced EndMT and pulmonary fibrosis.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 2116-2124"},"PeriodicalIF":3.743,"publicationDate":"2017-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00247E","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3791187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of GARP in the activation of latent TGF-β1","authors":"Julie Stockis, Olivier Dedobbeleer and Sophie Lucas","doi":"10.1039/C7MB00251C","DOIUrl":"https://doi.org/10.1039/C7MB00251C","url":null,"abstract":"<p >TGF-β1, 2 and 3 cytokines are involved in many cellular processes including cell proliferation, differentiation, migration and survival. Whereas TGF-β2 and 3 play important roles in embryonic development, TGF-β1 is mostly implicated in controlling immune responses after birth. The production of TGF-β1 is a tightly regulated process, occurring mostly at a post-translational level. Virtually all cells produce the latent, inactive form of TGF-β1. In latent TGF-β1, the mature TGF-β1 dimer is non-covalently associated to the Latency Associated Peptide, or LAP, which prevents binding to the TGF-β1 receptor. Activation of the cytokine implies release of mature TGF-β1 from LAP. Only a few cell types activate latent TGF-β1, <em>via</em> mechanisms that are cell type specific. Proteins such as integrins, proteases and thrombospondin-1 activate TGF-β1 in epithelial cells, fibroblasts and dendritic cells. More recently, the protein GARP was shown to be involved in TGF-β1 activation by regulatory T cells (Treg), a subset of CD4<small>⁺</small> T lymphocytes specialized in suppression of immune responses. GARP is a transmembrane protein that binds latent-TGF-β1 and tethers it on the Treg surface. The role of GARP was studied mostly in Tregs, and this was recently reviewed in L. Sun, H. Jin and H. Li, <em>Oncotarget</em>, 2016, <strong>7</strong>, 42826–42836. However, GARP is also expressed in non-immune cells. This review focuses on the roles of GARP in latent TGF-β1 activation by immune and non-immune cells.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 1925-1935"},"PeriodicalIF":3.743,"publicationDate":"2017-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00251C","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3762225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"RNA-sequencing dissects the transcriptome of polyploid cancer cells that are resistant to combined treatments of cisplatin with paclitaxel and docetaxel†","authors":"Qianqian Wang, Fei Lu and Rongfeng Lan","doi":"10.1039/C7MB00334J","DOIUrl":"https://doi.org/10.1039/C7MB00334J","url":null,"abstract":"<p >Overcoming chemoresistance will prevent cancer relapse and contribute to clinical chemotherapy. In order to explore the underlying mechanism of chemoresistance, we firstly incubated cancer cells with a combination of cisplatin + paclitaxel (C + P) or cisplatin + paclitaxel + docetaxel (C + P + D) to mimic the treatment of cancer therapy in the laboratory. We found that polyploidy is a recurring strategy that cells adopt in response to cisplatin-based treatments. RNA-sequencing was performed to identify differentially expressed genes (DEGs) that may contribute to drug resistance. 4830 and 5518 DEGs were discovered in C + P and C + P + D resistant cells, respectively, and 4384 (73.40%) genes were shared. Possible drug resistance genes like Atg14, Abcb1b, Tbx2, Slc2a9, Slc10a3 and Slc22a18 were up-regulated while Foxm1, Bcl2, Brca1, Chek1, Hiatl1 and Abcb9 were down regulated. Genes involved in the pathways of p53 signaling, lysosomes and apoptosis were up-regulated, and in contrast, genes in the cell cycle, DNA replication, and mismatch repair pathways were down-regulated. Moreover, representative proteins relative to DEGs were examined to validate the results of RNA-seq and RT-PCR. Taken together, these results will contribute to revealing the mechanism of chemoresistance and discovering potential prognostic factors for cancer medication.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 2125-2134"},"PeriodicalIF":3.743,"publicationDate":"2017-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00334J","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3791188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proximity aptasensor for protein detection based on an enzyme-free amplification strategy†","authors":"Dawei Yang, Yuguo Tang, Zhenzhen Guo, Xifeng Chen and Peng Miao","doi":"10.1039/C7MB00458C","DOIUrl":"https://doi.org/10.1039/C7MB00458C","url":null,"abstract":"<p >A novel electrochemical aptasensor for the detection of trace protein is proposed based on proximity binding-induced strand displacement and hybridization chain reaction. This method is proven to be highly selective and has potential practical utility, and offers new opportunities for the convenient detection of proteins with an enzyme-free amplification process.</p>","PeriodicalId":90,"journal":{"name":"Molecular BioSystems","volume":" 10","pages":" 1936-1939"},"PeriodicalIF":3.743,"publicationDate":"2017-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1039/C7MB00458C","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3762227","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}