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| 1 | Pivotal role of long non-coding ribonucleic acid-X-inactive specific transcript in regulating immune checkpoint programmed death ligand 1 through a shared pathway between miR-194-5p and miR-155-5p in hepatocellular carcinoma显示文摘BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the spotlight.However,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint blockade.Non-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic modulation.Given the wide range of ncRNAs that co-opt in programmed cell-death protein 1(PD-1)/programmed death ligand 1(PD-L1)regulation,and based on the literature,we hypothesized that miR-155-5p,miR-194-5p and long non-coding RNAs(lncRNAs)X-inactive specific transcript(XIST)and MALAT-1 are involved in a regulatory upstream pathway for PD-1/PD-L1.Recently,nutraceutical therapeutics in cancers have received increasing attention.Thus,it is interesting to study the impact of oleuropein on the respective study key players.AIM To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/PD-L1.METHODS Bioinformatics tools including microrna.org and lnCeDB software were adopted to detect targeting of miR-155-5p,miR-194-5p and lncRNAs XIST and MALAT-1 to PD-L1 mRNA,respectively.In addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and MALAT-1.HCC and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 expression.To study the interaction among miR-155-5p,miR-194-5p,lncRNAs XIST and MALAT-1,as well as PD-L1 mRNA,a series of transfections of the Huh-7 cell line was carried out.RESULTS Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and XIST.MALAT-1 and XIST were predicted to target PD-L1 mRNA.PD-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely detected.MiR-194 induced expression elevated the expression of PD-L1,XIST and MALAT-1.However,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MALAT-1 expression.Knockdown of XIST did have an impact on PD-L1 expression;however,following knockdown of the negative regulator of X-inactive specific transcript(TSIX),PD-L1 expression was elevated,and abolished MALAT-1 activity.Upon co-transfection of miR-194-5p with siMALAT-1,PD-L1 expression was elevated.Co-transfection of miR-194-5p with siXIST did not have an impact on PD-L1 expression.Upon co-transfection of miR-194 with siTSIX,PD-L1 expression was upregulated.Interestingly,the same PD-L1 expression pattern was observed following miR-155-5p cotransfections.Oleuropein treatment of Huh-7 cells reduced the expression profile of PD-L1,XIST,and miR-155-5p,upregulated the expression of miR-194-5p and had no significant impact on the MALAT-1 expression profile.CONCLUSION This study reported a novel finding revealing that opposing acting miRNAs in HCC,have the same impact on PD-1/PD-L1 immune checkpoint by sharing a common signaling pathway. | Sara M Atwa Heba Handoussa Karim M Hosny Margarete Odenthal Hend M El Tayebi | 2020 | World Journal of Hepatology2020，12，12： | 9 |
| 2 | Reliability evaluation for distribution system with renewable distributed generation during islanded mode of operation显示文摘 | Atwa Yasser M | 2009 | IEEE Trans on Power Systems2009，24，2： | 1 |
| 3 | Reliability Evaluation for Distribution System with Renewable Distributed Generation during Islanded Mode of Operation显示文摘 | Atwa Y M El-Saadany E F | 2009 | IEEE Transactions on Power Systems2009，24，2： | 1 |
| 4 | Supply adequacy assessment of distribution system including wind-based DG during different modes of operation显示文摘 | ATWA Y M EI-SAADANY E F GUISE A C | 2010 | IEEE Transactions on Power Systems2010，25，1： | 1 |
| 5 | Optimal renewable resources mix for distribution system energy loss minimization显示文摘 | Y M Atwa E F El-Saadany M M A Salama | 2010 | Power Systems IEEE Transactions on2010，25，1： | 1 |
| 6 | DG alloca- tion for benefit maximization in distribution net- works 显示文摘 | M F Shaaban Y M Atwa E F EkSaadany | 2013 | Power Systems IEEE Transactions on2013，28，2： | 1 |
| 7 | Optical ,structural and optoelec- tronic properties of pulsed laser deposition PbS thin film 显示文摘 | Atwa D M M Azzouz I M Badr Y | 2011 | Applied Physics B2011，103，1： | 1 |
| 8 | Immunoglobulins from Graves′disease patients stimulate phospholipase A2 and C systems in FRTL-5 and human thyroid cells显示文摘 | Atwa M A Smallridge R C Burch H B | | 0，，： | 1 |
| 9 | Optimal allocation of ESS indistribution systems with a high penetration of wind energy显示文摘 | Atwa Y M El-Saadany E F | 2010 | IEEE Transactions on Power Systems2010，25，4： | 1 |
| 10 | Reliability evaluation for distribution system with renewable distributed generation during islanded mode of operation显示文摘 | ATWA Y M EL-SAADANY E F | 2009 | IEEE Trans on Power Systems2009，24，2： | 1 |
| 11 | Opti- mal renewable resources mix for distribution system energy loss minimization 显示文摘 | ATWA Y M EL-SAADANY E F SALAMA M M A | 2010 | 1EEE Transactions on Power Systems2010，25，1： | 1 |
| 12 | Adequacy evaluation of distribution system including wind/solar DG during different modes of operation显示文摘 | ATWA Y M SAADANY E F SALAMA M M A | | 0，，04： | 1 |
| 13 | Optimal renewable resources mix for distribution system energy loss minimization显示文摘 | Atwa Y M E1-Saadany E F Salama M M A | 2010 | IEEE Transactions on Power Systems2010，25，1： | 1 |
| 14 | Probabilistic approach for optimal allocation of wind-based distributed generation in distribution systems显示文摘 | ATWA Y M EL-SAADANY E F | 2011 | IET Renewable Power Generation2011，5，1： | 1 |
| 15 | Adequacy Evaluation of Distribution System Including Wind/ Solar DG During Different Modes of Operation 显示文摘 | ATWA Y M EL-SAADANY E F SALAMA M M A | 2011 | IEEE Transactions on Power Systems2011，26，4： | 1 |
| 16 | Reliability evaluation for distribution system with renewable distributed generation during islanded mode of operation显示文摘 | ATWA Y M EI-SAADANY E F | 2009 | IEEE Trans on Power Systems2009，24，2： | 1 |
| 17 | PEVs modeling and impacts mitigation in distribution networks显示文摘 | Shaaban M F Atwa Y M El-Saadany E F | 2013 | IEEE Transactions on Power Systems2013，28，2： | 1 |
| 18 | Optimal renewable resources mix for distribu- tion system energy loss minimization 显示文摘 | ATWA Y M | 2010 | IEEE Transac- lions on Power Systems2010，25，1： | 1 |
| 19 | Optical, structural and optoelectronic properties of pulsed laser deposition PbSthin film 显示文摘 | Atwa D M M Azzouz I M Badr Y | 2011 | Appl Phys B2011，103，1： | 1 |
| 20 | Opti-mal renewable resources mix for distribution system ener-gy loss minimization显示文摘 | Atwa Y M El-Saadany E F Salama M M A | 2010 | Power Systems IEEE Transac-tions on2010，25，1： | 1 |
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