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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

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World Journal of Hepatology 2020年第12期12卷 1211-1227页

作者： Sara M Atwa heba handoussa Karim M Hosny Margarete Odenthal Hend M El Tayebi Pharmaceutical Biology Department German University in CairoCairo 11865Egypt Department of General Surgery Faculty of MedicineCairo UniversityCairo 11562Egypt Institute for Pathology University Hospital CologneCologne 50924Germany Molecular Pharmacology Research Group Department of Pharmacology and ToxicologyFaculty of Pharmacy and BiotechnologyGerman University in CairoCairo 11835Egypt

BACKGROUND Anti-programmed death therapy has thrust immunotherapy into the ***,such therapy has a modest response in hepatocellular carcinoma(HCC).Epigenetic immunomodulation is a suggestive combinatorial therapy with immune checkpoint ***-coding ribonucleic acid(ncRNA)driven regulation is a major mechanism of epigenetic *** 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/***,nutraceutical therapeutics in cancers have received increasing ***,it is interesting to study the impact of oleuropein on the respective study key *** To explore potential upstream regulatory ncRNAs for the immune checkpoint PD-1/*** Bioinformatics tools including *** 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,*** addition,Diana tool was used to predict targeting of both aforementioned miRNAs to lncRNAs XIST and *** and normal tissue samples were collected for scanning of PD-L1,XIST and MALAT-1 *** 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 *** Bioinformatics software predicted that miR-155-5p and miR-194-5p can target PDL1,MALAT-1 and ***-1 and XIST were predicted to target PD-L1 ***-L1 and XIST were significantly upregulated in 23 HCC biopsies compared to healthy controls;however,MALAT-1 was barely ***-194 induced expression elevated the expression of PD-L1,XIST and ***,overexpression of miR-155-5p induced the upregulation of PD-L1 and XIST,while it had a negative impact on MA

关键词： Hepatocellular carcinoma X-inactive specific transcript MiR-155-5p MiR-194-5p Programmed cell-death protein 1/Programmed death ligand 1 Immune checkpoint

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Uncoupling tumor necrosis factor-αand interleukin-10 at tumor immune microenvironment of breast cancer through miR-17-5p/MALAT-1/H19 circuit

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BIOCELL 2022年第3期46卷 769-783页

作者： RAGHDA A.SOLIMAN RANA A.YOUNESS TAMER M.MANIE EMAD KHALLAF MOHAMED EL-SHAZLY MONA ABDELMOHSEN heba handoussa MOHAMED Z.GAD Pharmaceutical Biology Department Faculty of Pharmacy and BiotechnologyGerman University in CairoCairo11835Egypt School of Life and Medical Sciences University of Hertfordshire Hosted by Global Academic FoundationNew Administrative Capital11578Egypt Breast Surgery Department National Cancer InstituteCairo UniversityCairoEgypt General Surgery Department Faculty of MedicineCairo UniversityCairoEgypt Department of Phytochemistry National Research CentreGiza12622Egypt Biochemistry Department Faculty of Pharmacy and BiotechnologyGerman University in CairoCairo11835Egypt

Triple Negative Breast Cancer(TNBC)immunotherapy has recently shown promising ***,some TNBC patients presented with *** of the reasons was attributed to the excessive release of cytokines at the tumor microenvironment(TME)such as Tumor necrosis factor alpha(TNF-α)and Interleukin-10(IL-10).Fine regulation of these cytokines’levels via non-coding RNAs(ncRNAs)might alleviate the immune quiescent nature of TME at TNBC ***,the extrapolation of ncRNAs as therapeutic tools is highly ***,disentanglement the nature for the isolation of natural compounds that could modulate the ncRNAs and their respective targets is an applicable translational therapeutic ***,this study aimed to targeting the chief immune suppressive cytokines at the TME(TNF-αand IL-10)via ncRNAs and to examine the effects of Rosemary aerial parts extract on the expression levels of these ncRNAs in *** revealed miR-17-5p as a dual regulator of TNF-αand ***,an intricate interaction has been shown between miR-17-5p and the oncogenic lncRNAs:MALAT1 and *** down of MALAT1 and/or H19 caused an induction in miR-17-5p and reduction in TNF-αand IL-10 expression ***-17-5p was found to be down-regulated,while TNF-α,IL-10,MALAT1 and H19 were up-regulated in BC *** expression of miR-17-5p in MDA-MB-231 cells reduced TNF-α,IL-10,MALAT1 and H19 expression levels,as well as several BC *** a translational approach,ursolic acid(UA)isolated from rosemary induced the expression of miR-17-5p,MALAT1 and decreased H19 expression *** conclusion,this study suggests miR-17-5p as a tumor suppressor and an immune-activator miRNA in BC through tuning up the immunological targets TNF-α,IL-10 at the TME and the oncological mediators MALAT1 and H19 lncRNAs.

关键词： Breast cancer Tumor microenvironment Cytokines TNF-α IL-10 miR-17-5p MALAT1 H19 lncRNAs miRNA Ursolic acid

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