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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 | Altered levels of the onco-microRNA 21 and the tumor-supressor microRNAs143 and 145 in advanced rectal cancer indicate successful neoadjuvant chemoradiotherapy显示文摘 | Uta Drebber Max Lay Inga Wedemeyer Daniel Vallb?hmer Elfriede Bollschweiler Jan Brabender Stefan M?nig Arnulf H?lscher Hans Dienes Margarete Odenthal | 2011 | International Journal of Oncology2011，，： | 2 |
| 3 | Factors of transforming growt h factor beta signalling are co-regulated in human hepatocellular carcinoma显示文摘 | Longerich T Breuhahn K Odenthal M | 2004 | Virchows Arch2004，445，6： | 1 |
| 4 | The role of insulin-like growth factor Ⅱ in the malignant transformation of rat liver oval cells显示文摘 | Zhang N Siegel K Odenthal M | 1997 | Hepatol1997，25，4： | 1 |
| 5 | 2-Dimensional Transition Metal Dichalcogenides with Tunable Direct Band Gaps MoSm-x Se2x Monolayers显示文摘 | Mann J Ma Q Odenthal P M | 2014 | Advanced Materials2014，26，9： | 1 |
| 6 | Long-term follow-up of the corneal endothelium after Artisan lens implantation for unilateral traumatic and unilateral congenital cataract in children two case series显示文摘 | ODENTHAL M P SMINIA M L PRICK L J | 2006 | Cornea2006，25，10： | 1 |
| 7 | Expression and functional interaction of hepatocyte growth factor-scatter factor and its receptor c-met in mammalian brain显示文摘 | Jung W Castren E Odenthal M | 1994 | J Cell Biol1994，126，2： | 1 |
| 8 | Expression and Functional interaction of hepatocyte growth factor-scatter factor and its Receptor c-met in mammalian brain显示文摘 | JUNG W CASTREN E ODENTHAL M | 1994 | The Journal of cell biology1994，126，2： | 1 |
| 9 | Factors of transfor ming growth factor beta signalling are co-regulated in human hepatocellular carcinoma显示文摘 | Longerich T Breuhahn K Odenthal M | 2004 | Virchows Arch2004，445，6： | 1 |
| 10 | Factors of transform?ing growth factor beta signalling are co-regulated in human hepato?cellular carcinoma显示文摘 | Longerich T Breuhahn K Odenthal M | 2004 | Virchows Arch2004，445，6： | 1 |
| 11 | The gene of hepatocyte growth factor is expressed in fat -storing cells of rat liver and is downregulated during cell growth and by transforming growth factor -beta显示文摘 | Ramadori G Neubauer K Odenthal M | 1992 | Biochem Biophys Res Commun1992，183，2： | 1 |
| 12 | The ceUflux storage concept for cost reduction in parabolic troughsolar thermal power plants显示文摘 | Odenthal C Steinmann W Eck M | 2014 | Energy Procedia2014，，46： | 1 |
| 13 | β-cateninand Her-2/neu expression in rectal cancer:associationwith histomorphological response to neoadjuvant thera-py and prognosis显示文摘 | Drebber U Madeja M Odenthal M | 2011 | Int J Colorectal Dis2011，26，9： | 1 |
| 14 | MicmRNA profiling in locally advanced esophageal cancer indicates a high potential of miR-192 in prediction of muhimodality therapy re- sponse显示文摘 | Odenthal M Bollschweiler E Grimminger PP | 2013 | Int J Cancer2013，133，10： | 1 |
| 15 | Synthesis of cellular fibronectin by rat liver fat-storing (Ito) cells: regulation by cytokines显示文摘 | Ramadori G Knittel T Odenthal M | 1992 | Gastroenterol1992，103，3： | 1 |
| 16 | Alternotive Splicing products of the tenascin gene distinguish rat liver storing cells from arterial smooth muscle cells and skin fibroblasts显示文摘 | Schwogler S Odenthal M Buschenfelde KH | 1992 | Biochem Biophys Rescommun1992，185，： | 1 |
| 17 | Developmental mutant screens in the zebrafish显示文摘 | Van Eeden F J Granato M Odenthal J | 1999 | Methods Cell Biol1999，60，： | 1 |
| 18 | The role of insulin-like growth factor Ⅱ in the malignant transformation of rat liver oval cells显示文摘 | Zhang N Siegel K Odenthal M | 1997 | Hepatol1997，25，4： | 1 |
| 19 | Atorvastatin attenuates hepatic fibrosis in rats after bile duct ligation via decreased turnover of hepatic stellate cells显示文摘 | Trebicka J Hennenberg M Odenthal M | 2010 | J Hepatol2010，53，4： | 1 |
| 20 | Mi- croRNA profiling in locally advanced esophageal cancer indicates a high potential of miR-192 in prediction of mul timodality therapy response显示文摘 | Odenthal M Bollschweiler E Grimminger PP | 2013 | Int J Cancer2013，133，10： | 1 |
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