MiR-155-regulated mTOR and Toll-like receptor 5 in gastric diffuse large B-cell lymphoma
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ABSTRACT:
PROVIDER: PRJNA756003 | ENA |
REPOSITORIES: ENA
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Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182359 | GEO
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182357 | GEO
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182361 | GEO
Project description:Background: Gastric diffuse large B-cell lymphoma (DLBCL) is often associated with Helicobacter pylori (H. pylori) infection. Early-stage gastric DLBCLs could be treated with H. pylori eradication therapy (HPET), and are classified into a sensitive group and a resistant group. Methods: Genome-wide miRNA and mRNA profiles were performed on gastric DLBCLs that had been treated with HPET. MicroRNAs and mRNAs preferentially associated with resistance or sensitivity to HPET were identified. Pathway enrichment and a miR-centered bioinformatic approach were also used. The candidate markers were further evaluated with a luciferase assay and Western blotting in BJAB or U2932 lymphoma cell lines of B-cell origin. These markers were verified in an independent series, and clinical and pathological correlations were established. Results: Genome-wide miRNA and mRNA profiles showed that the resistant group had higher levels of miR-155 and lower levels of DEPTOR (an inhibitor of mTOR) than the sensitive group. BJAB cells transfected with miR-155 also had lower DEPTOR and higher mTOR levels. Therefore, miR-155-mediated inhibition of DEPTOR with secondary activation of mTOR was a potential marker for resistance HPET. In contrast, pathway enrichment analysis showed that Toll-like receptor 5 (TLR5), the receptor for bacterial flagellin, was a potential marker for sensitivity to HPET. In an independent series, stronger expression of pS6K1 (a direct target of mTOR) was associated with the resistant group, and morphologic evidence of active gastritis was associated with the sensitive group. Conclusions: These findings showed that miR-155 and TLR5 were markers for resistance and sensitivity to HPET. Furthermore, histological evaluation of active gastritis might be used as a surrogate marker to predict responsiveness to HPET in gastric DLBCL. These data also suggested the possibility that mTOR inhibitors might be used in gastric DLBCLs resistant to HPET.
2022-02-09 | GSE182358 | GEO
Project description:This SuperSeries is composed of the SubSeries listed below.
2022-02-09 | GSE182362 | GEO
Project description:The mechanistic target of rapamycin, (mTOR) kinase plays a pivotal role in controlling critical cellular growth and survival pathways, and its aberrant induction is implicated in cancer pathogenesis. Therefore, suppression of active mTOR signaling has been of great interest to researchers; several mTOR inhibitors have been discovered to date. Ethanol (EtOH), similar to pharmacologic mTOR inhibitors, has been shown to suppress the mTOR signaling pathway, though in a non-catalytic manner. Despite population studies showing that the consumption of EtOH has a protective effect against hematological malignancies, the mechanisms behind EtOHM-bM-^@M-^Ys modulation of mTOR activity in cells and its downstream consequences are largely unknown. Here we evaluated the effects of EtOH on the mTOR pathway, in comparison to the active-site mTOR inhibitor INK128, and compared translatome analysis of their downstream effects in diffuse large B-cell lymphoma (DLBCL). SUDHL-2 and SUDHL-4 diffuse large B-cell lymphoma (DLBCL) cell lines (ATCC) were cultured in RPMI Medium 1640 (Gibco BRL) supplemented with 10% fetal bovine serum (FBS) at 37M-BM-0C in 5% CO2. EtOH-treated cells were cultured in sealed flasks to maintain EtOH concentrations, 20mM in the culture medium, water was added to EtOH control wells. INK128-treated cells were treated with INK128 at 40nM (Selleckchem) dissolved in dimethyl sulfoxide (DMSO) or 0.01% DMSO was added for the control wells. To create polysomal fractions, cells were lysed in cytoplasmic lysis buffer (5mM Tris, 2.5mM MgCl2, 1.5mM KCl, 1% Triton X-100, 0.5% Sodium Deoxycholate and 2 mM DTT), loaded on 10 - 50% linear sucrose gradients and fractionated. The RNA in each fraction was monitored by optical density measurement (A254) and eleven fractions were collected with a fraction collector (Brandel). The RNA from each fraction was isolated by Trizol (Invitrogen) and used for RT-qPCR analysis. RNA from high molecular weight polysomal fractions, with actively translated mRNAs (fractions 9 - 11) were pooled and used for microarray analysis. RNA was isolated using Qiagen RNeasy protocols and quality and quantity were checked with an Agilent 2100 Bio-Analyzer using RNA 6000 Nano chips. Labeling and amplification were done with the standard Illumina protocol and the biotin-labeled cRNA was hybridized to Illumina's HumanHT-12 V4.0 Expression BeadChip. The arrays were washed, blocked and the biotin-labeled cRNA was detected by staining with streptavidin-Cy3.
2015-03-03 | E-GEOD-62790 | biostudies-arrayexpress
Project description:The mechanistic target of rapamycin, (mTOR) kinase plays a pivotal role in controlling critical cellular growth and survival pathways, and its aberrant induction is implicated in cancer pathogenesis. Therefore, suppression of active mTOR signaling has been of great interest to researchers; several mTOR inhibitors have been discovered to date. Ethanol (EtOH), similar to pharmacologic mTOR inhibitors, has been shown to suppress the mTOR signaling pathway, though in a non-catalytic manner. Despite population studies showing that the consumption of EtOH has a protective effect against hematological malignancies, the mechanisms behind EtOH’s modulation of mTOR activity in cells and its downstream consequences are largely unknown. Here we evaluated the effects of EtOH on the mTOR pathway, in comparison to the active-site mTOR inhibitor INK128, and compared translatome analysis of their downstream effects in diffuse large B-cell lymphoma (DLBCL).
2015-03-03 | GSE62790 | GEO
Project description:mTOR and Toll-like receptor 5 in gastric diffuse large B-cell lymphoma as markers for resistance and sensitivity to H. pylori eradication therapy
| PRJNA756008 | ENA
Project description:miR-155 inhibits DEPTOR in gastric diffuse large B-cell lymphoma resistant to H. pylori eradication therapy
| PRJNA755999 | ENA
Project description:The negative feedback mechanism is essential to maintain effective immunity and tissue homeostasis. 1,25-dihydroxyvitamin D (1,25(OH)2D3) modulates innate immune response, but the mechanism remains poorly understood. Here we report that vitamin D receptor (VDR) signaling attenuates Toll-like receptor-mediated inflammation by enhancing the negative feedback inhibition. VDR inactivation leads to a hyperinflammatory response in mice and macrophage cultures when challenged with lipopolysaccharide (LPS) due to miR-155 overproduction that excessively suppresses SOCS1, a key regulator that enhances the negative feedback loop. Deletion of miR-155 attenuates vitamin D suppression of LPS-induced inflammation, confirming that 1,25(OH)2D3 stimulates SOCS1 by down-regulating miR-155. 1,25(OH)2D3 down-regulates bic transcription by inhibiting NF-kappaB activation, which is mediated by a kappaB cis-DNA element located within the first intron of the bic gene. Together these data identify a novel regulatory mechanism for vitamin D to control innate immunity.
2013-01-05 | GSE43300 | GEO