Psoriasis is a chronic non-contagious autoimmune disease. Gallic acid is a natural compound with potential health benefits, including antioxidant, anticancer, antiviral and antibacterial properties. Nevertheless, the influence of gallic acid on psoriasis has not been fully determined. This investigation aimed to discover the effect of gallic acid on psoriasis. Thirty-one pairs of psoriatic skin tissues and healthy adult human skin tissues were collected. Human keratinocytes (HaCaT cells) were transfected with interleukin 17A (IL-17A) to create the psoriatic keratinocyte model. The content of bromodomain-containing protein 4 (BRD4) microRNA was assessed using qRT-PCR testing. The content of BRD4 was detected by Western blotting. Cell migration was evaluated by conducting a wound healing assay. Cell proliferation was determined using an EdU assay. Apoptosis was detected by the TUNEL assay. The contents of interferon gamma (IFN-γ), IL-6, IL-8 and IL-17 were detected by ELISA. BRD4 was up-regulated in psoriatic skin tissues and in the IL-17A group compared to the healthy adult human skin tissues and the control group. Silencing BRD4 inhibited cell migration, proliferation and inflammatory response but induced apoptosis in IL-17A-treated HaCaT cells. Conversely, BRD4 over-expression promoted cell migration, proliferation and inflammatory response but suppressed apoptosis in IL-17A-treated HaCaT cells. Gallic acid repressed cell migration, proliferation and inflammatory response but indu-ced apoptosis in HaCaT cells transfected with IL-17A by down-regulating BRD4. Gallic acid represses cell migration, proliferation and inflammatory response but induces apoptosis in IL-17A-transfected HaCaT cells by down-regulating BRD4.
- Klíčová slova
- BRD4, gallic acid, hyperproliferation, inflammation, keratinocytes, psoriasis,
- MeSH
- apoptóza * účinky léků MeSH
- buněčné linie keratinocytů HaCaT MeSH
- buněčné linie MeSH
- dospělí MeSH
- interleukin-17 metabolismus MeSH
- jaderné proteiny metabolismus genetika MeSH
- keratinocyty * účinky léků metabolismus MeSH
- kyselina gallová * farmakologie MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- pohyb buněk * účinky léků MeSH
- proliferace buněk * účinky léků MeSH
- proteiny buněčného cyklu * metabolismus genetika MeSH
- proteiny obsahující bromodoménu MeSH
- psoriáza * metabolismus patologie farmakoterapie MeSH
- regulace genové exprese účinky léků MeSH
- transkripční faktory * metabolismus MeSH
- zánět * patologie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- BRD4 protein, human MeSH Prohlížeč
- interleukin-17 MeSH
- jaderné proteiny MeSH
- kyselina gallová * MeSH
- mikro RNA MeSH
- proteiny buněčného cyklu * MeSH
- proteiny obsahující bromodoménu MeSH
- transkripční faktory * MeSH
Protein hydroxylation affects protein stability, activity, and interactome, therefore contributing to various diseases including cancers. However, the transiency of the hydroxylation reaction hinders the identification of hydroxylase substrates. By developing an enzyme-substrate trapping strategy coupled with TAP-TAG or orthogonal GST- purification followed by mass spectrometry, we identify adenylosuccinate lyase (ADSL) as an EglN2 hydroxylase substrate in triple negative breast cancer (TNBC). ADSL expression is higher in TNBC than other breast cancer subtypes or normal breast tissues. ADSL knockout impairs TNBC cell proliferation and invasiveness in vitro and in vivo. An integrated transcriptomics and metabolomics analysis reveals that ADSL activates the oncogenic cMYC pathway by regulating cMYC protein level via a mechanism requiring ADSL proline 24 hydroxylation. Hydroxylation-proficient ADSL, by affecting adenosine levels, represses the expression of the long non-coding RNA MIR22HG, thus upregulating cMYC protein level. Our findings highlight the role of ADSL hydroxylation in controlling cMYC and TNBC tumorigenesis.
- MeSH
- adenosin metabolismus MeSH
- adenylsukcinátlyasa genetika metabolismus MeSH
- karcinogeneze MeSH
- lidé MeSH
- mikro RNA genetika metabolismus MeSH
- nádorové buněčné linie MeSH
- proliferace buněk MeSH
- prolyl-4-hydroxylasy HIF genetika metabolismus MeSH
- protoonkogenní proteiny c-myc genetika metabolismus MeSH
- triple-negativní karcinom prsu enzymologie genetika patofyziologie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- adenosin MeSH
- adenylsukcinátlyasa MeSH
- EGLN2 protein, human MeSH Prohlížeč
- mikro RNA MeSH
- MIRN22 microRNA, human MeSH Prohlížeč
- MYC protein, human MeSH Prohlížeč
- prolyl-4-hydroxylasy HIF MeSH
- protoonkogenní proteiny c-myc MeSH
To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
- MeSH
- celogenomová asociační studie metody MeSH
- genetická predispozice k nemoci genetika MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus genetika MeSH
- kolorektální nádory genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- rizikové faktory MeSH
- RNA dlouhá nekódující genetika MeSH
- senioři MeSH
- signální transdukce genetika MeSH
- studie případů a kontrol MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- Názvy látek
- RNA dlouhá nekódující MeSH
