We aimed to shed new light on the roles of microRNAs （miRNAs） in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and app...We aimed to shed new light on the roles of microRNAs （miRNAs） in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and applied to the 26 highly differentially deregulated miRNAs in hepatocellular carcinoma. This framework comprises： （1） the overlap of prediction results by four out of five target prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB （combining machine-learning, alignment, interaction energy and statistical tests in order to minimize false positives）, （2） evidence from previous microarray analysis on the expression of these targets, （3） gene ontology （GO） and pathway enrichment analysis of the miRNA targets and their pathways and （4） linking these results to oncogenesis and cancer hallmarks. This yielded new insights into the roles of miRNAs in cancer hallmarks. Here we presented several key targets and hundreds of new targets that are significantly enriched in many new cancer-related hallmarks. In addition, we also revealed some known and new oncogenic pathways for liver cancer. These included the famous MAPK, TGFβ and cell cycle pathways. New insights were also provided into Wnt signaling, prostate cancer, axon guidance and oocyte meiosis pathways. These signaling and developmental pathways crosstalk to regulate stem cell transformation and implicate a role of miRNAs in hepatic stem cell deregulation and cancer development. By analyzing their complete interactome, we proposed new categorization for some of these miRNAs as either tumor-suppressors or oncomiRs with dual roles. Therefore some of these miRNAs may be addressed as therapeutic targets or used as therapeutic agents. Such dual roles thus expand the view of miRNAs as active maintainers of cellular homeostasis.展开更多
Background: Adipose-derived stem cells (ASCs) are considered ideal candidates for both research and cellular therapydue to ease of access, large yield, feasibility, and efficacy in preclinical and clinical studies. Un...Background: Adipose-derived stem cells (ASCs) are considered ideal candidates for both research and cellular therapydue to ease of access, large yield, feasibility, and efficacy in preclinical and clinical studies. Unlike the subcutaneousabdominal fat depot, breast ASCs features are still not well recognized, limiting their possible therapeutic use. ASCswere found to exert immunomodulatory and antioxidative activities for maintaining homeostasis and functionality ofdiseased/damaged tissues. This study aims to investigate the immunomodulatory and antioxidative potentials of breastversus abdominal isolated ASCs to find out which anatomical site provides ASCs with better immunoregulatory andoxidative stress resistance capabilities.Methods: ASCs were isolated from abdominal and breast tissues. Gene expression analysis was conducted for a panelof immunomodulatory and antioxidative genes, as well as adipokines and proliferation genes. Flow cytometric analysisof a group of immunomodulatory surface proteins was also performed. Finally, the significantly expressed genes haveundergone protein-protein interaction and functional enrichment in silico analyses.Results: Our results revealed similar morphological and phenotypic characteristics for both breast and abdominalASCs. However, a significant elevation in the expression of two potent immunosuppressive genes, IL-10 and IDO aswell as the expression of the multifaceted immunomodulatory adipokine, visfatin, was detected in breast versusabdominal ASCs. Moreover, a significant overexpression of the antioxidative genes, GPX1, SIRT5, and STAT3 and theproliferation marker, Ki67, was also observed in breast ASCs relative to abdominal ones. In silico analysis showed thatboth of the differentially upregulated immunomodulatory and antioxidative mediators integratively involved inmultiple biological processes and pathways indicating their functional association.Conclusion: Breast ASCs possess superior immunomodulatory and antioxidative capabilities over abdominal ASCs. Ourfindings shed light on the possible therapeutic applications of breast ASCs in immune-related and oxidative stressassociateddiseases.展开更多
基金partial support through Science and Technology Development Fund (STDF) by Egyptian Ministry of Scientifc Research (Grant No.1169 and 1679)
文摘We aimed to shed new light on the roles of microRNAs （miRNAs） in liver cancer using an integrative in silico bioinformatics analysis. A new protocol for target prediction and functional analysis is presented and applied to the 26 highly differentially deregulated miRNAs in hepatocellular carcinoma. This framework comprises： （1） the overlap of prediction results by four out of five target prediction tools, including TargetScan, PicTar, miRanda, DIANA-microT and miRDB （combining machine-learning, alignment, interaction energy and statistical tests in order to minimize false positives）, （2） evidence from previous microarray analysis on the expression of these targets, （3） gene ontology （GO） and pathway enrichment analysis of the miRNA targets and their pathways and （4） linking these results to oncogenesis and cancer hallmarks. This yielded new insights into the roles of miRNAs in cancer hallmarks. Here we presented several key targets and hundreds of new targets that are significantly enriched in many new cancer-related hallmarks. In addition, we also revealed some known and new oncogenic pathways for liver cancer. These included the famous MAPK, TGFβ and cell cycle pathways. New insights were also provided into Wnt signaling, prostate cancer, axon guidance and oocyte meiosis pathways. These signaling and developmental pathways crosstalk to regulate stem cell transformation and implicate a role of miRNAs in hepatic stem cell deregulation and cancer development. By analyzing their complete interactome, we proposed new categorization for some of these miRNAs as either tumor-suppressors or oncomiRs with dual roles. Therefore some of these miRNAs may be addressed as therapeutic targets or used as therapeutic agents. Such dual roles thus expand the view of miRNAs as active maintainers of cellular homeostasis.
基金This work was funded by the National Research Centre,Cairo,Egypt(grant no.11010122)the Academy of Scientific Research and Technology in Egypt“Jesor initiative”(grant no.1057).
文摘Background: Adipose-derived stem cells (ASCs) are considered ideal candidates for both research and cellular therapydue to ease of access, large yield, feasibility, and efficacy in preclinical and clinical studies. Unlike the subcutaneousabdominal fat depot, breast ASCs features are still not well recognized, limiting their possible therapeutic use. ASCswere found to exert immunomodulatory and antioxidative activities for maintaining homeostasis and functionality ofdiseased/damaged tissues. This study aims to investigate the immunomodulatory and antioxidative potentials of breastversus abdominal isolated ASCs to find out which anatomical site provides ASCs with better immunoregulatory andoxidative stress resistance capabilities.Methods: ASCs were isolated from abdominal and breast tissues. Gene expression analysis was conducted for a panelof immunomodulatory and antioxidative genes, as well as adipokines and proliferation genes. Flow cytometric analysisof a group of immunomodulatory surface proteins was also performed. Finally, the significantly expressed genes haveundergone protein-protein interaction and functional enrichment in silico analyses.Results: Our results revealed similar morphological and phenotypic characteristics for both breast and abdominalASCs. However, a significant elevation in the expression of two potent immunosuppressive genes, IL-10 and IDO aswell as the expression of the multifaceted immunomodulatory adipokine, visfatin, was detected in breast versusabdominal ASCs. Moreover, a significant overexpression of the antioxidative genes, GPX1, SIRT5, and STAT3 and theproliferation marker, Ki67, was also observed in breast ASCs relative to abdominal ones. In silico analysis showed thatboth of the differentially upregulated immunomodulatory and antioxidative mediators integratively involved inmultiple biological processes and pathways indicating their functional association.Conclusion: Breast ASCs possess superior immunomodulatory and antioxidative capabilities over abdominal ASCs. Ourfindings shed light on the possible therapeutic applications of breast ASCs in immune-related and oxidative stressassociateddiseases.
