Circular RNAs (circRNAs) represent a class of non-coding RNAs that are widely expressed in mammals. However, it is largely unknown about the function of human circRNAs and the roles of circRNAs in human oral squamous cell carcinomas (OSCC). Here we performed a comprehensive study of circRNAs in human OSCC using circRNA and mRNA microarrays, and identified many circRNAs that are differentially expressed between OSCC tissue and paired non-cancerous matched tissue. We further found a circRNA termed circRNA_100290 that served as a critical regulator in OSCC development. We discovered that circRNA_100290 was upregulated and co-expressed with CDK6 in OSCC tissue. Knockdown of circRNA_100290 decreased expression of CDK6 and inhibited proliferation of OSCC cell lines in vitro and in vivo. Via luciferase reporter assays, circRNA_100290 was observed to directly bind to miR-29 family members. Further EGFP/RFP reporter assays showed that CDK6 was the direct target of miR-29b. Taken together, we conclude that circRNA_100290 may function as a competing endogenous RNA to regulate CDK6 expression through sponging up miR-29b family members. Taken together, it indicates that circRNAs may exert regulatory functions in OSCC and may be a potential target for OSCC therapy.

Material

Interferon regulatory factor 3 (IRF3) regulates early type I IFNs and other genes involved in innate immunity. We have previously shown that cells undergoing an endoplasmic reticulum (ER) stress response called the “Unfolded Protein Response” (UPR) produce synergistically augmented IFN-β when stimulated with pattern recognition receptor agonists such as LPS Concomitant ER stress and LPS stimulation resulted in greater recruitment of the IRF3 transcription factor to ifnb1 gene regulatory elements. In this study, we utilized murine cells to demonstrate that both oxygen-glucose deprivation and pharmacologic UPR inducers trigger phosphorylation and nuclear translocation of IRF3, even in the absence of exogenous LPS. Different ER stressors utilized distinct mechanisms to activate IRF3: IRF3 phosphorylation due to calcium-mobilizing ER stress (thapsigargin treatment, oxygen-glucose deprivation) critically depended upon Stimulator of interferon gene (STING), an ER-resident nucleic acid-responsive molecule. However, calcium mobilization alone by ionomycin was insufficient for IRF3 phosphorylation. In contrast, other forms of ER stress (e.g., tunicamycin treatment) promote IRF3 phosphorylation independently of STING and Tank binding kinase 1 (TBK1). Rather, IRF3 activation by tunicamycin and 2-deoxyglucose was inhibited by AEBSF, a serine protease inhibitor that blocks ATF6 processing. Interfering with ER stress-induced IRF3 activation abrogated IFN-β synergy. Together, these data suggest ER stress primes cells to respond to innate immune stimuli by activating the IRF3 transcription factor. Our results also suggest certain types of ER stress accomplish IRF3 phosphorylation by co-opting existing innate immune pathogen response pathways. These data have implications for diseases involving ER stress and type I IFN.

OBJECTIVE Previous work from the HLA-B27 transgenic rat model of ankylosing spondylitis (AS) suggests that macrophages develop an intracellular stress response called the Unfolded Protein Response (UPR) and as a result secrete increased cytokines in response to Toll like receptor agonists such as lipopolysaccharide (LPS). Our objective was to determine if macrophages from AS patients also undergo an UPR and secrete increased cytokines/chemokines in response to LPS. METHODS Peripheral blood monocytes isolated from 10 AS patients and healthy controls were differentiated in vitro with M-CSF. Select samples were treated with IFN-γ to up-regulate MHC class I (HLA-B) expression prior to stimulation with LPS for 3h (for RNA collection), or 8–24h (for supernatant collection). UPR induction was assessed by expression of ERdj4, BiP and CHOP mRNA. RESULTS Although IFN-γ treatment up-regulated HLA-B expression 2-fold(p=0.0094), neither IFN-γ nor LPS enhanced BiP or CHOP expression substantially (<1.3 fold). ERdj4 expression increased weakly but insignificantly in IFN-γ+LPS AS samples (2.2 fold, p=0.31). In response to LPS, AS macrophages secreted more CXCL9, IL-10, IL-12p70, IL-23, and TNF-α than controls(p ≤ 0.025)The most striking difference was observed for IL-23 (median AS patient 265 pg/mL vs. control 9 pg/mL, p=0.0007). We did not detect significant differences in IL-6, IL-8, or IFN-β production. CONCLUSIONS Greater IL-23 production by AS patient macrophages in response to LPS provides further support for the development of Th17/IL23-directed therapy. Since significant UPR induction was not detected in AS patient macrophages, the relationship between UPR and inflammatory cytokine production remains unclear.

Background/Aims: Prostate cancer (PCa) is one of the main cancers that damage males’ health severely with high morbidity and mortality, but there is still no ideal molecular marker for the diagnosis and prognosis of prostate cancer. Methods: To determine whether the differentially expressed circRNAs in prostate cancer can serve as novel biomarkers for prostate cancer diagnosis, we screened differentially expressed circRNAs using SBC-ceRNA array in 4 pairs of prostate tumor and paracancerous tissues. A circRNA-miRNA-mRNA regulatory network for the differential circRNAs and their host genes was constructed by Cytoscape3.5.1 software. Quantitative real-time polymerase chain reaction analysis (qRT-PCR) was performed to confirm the microarray data. Results: We found 1021 differentially expressed circRNAs in PCa tumor using SBC-ceRNA array and confirmed the expression of circ_0057558, circ_0062019 and SLC19A1 in PCa cell lines and tumor tissues through qRT-PCR analysis. We demonstrated that combination of PSA level and two differentially expressed circRNAs showed significantly increased AUC, sensitivity and specificity (0.938, 84.5% and 90.9%, respectively) than PSA alone (AUC of serum PSA was 0.854). Moreover, circ_0057558 was correlated positively with total cholesterol. The functional network of circRNA-miRNA-mRNA analysis showed that circ_0057558 and circ_0034467 regulated miR-6884, and circ_0062019 and circ_0060325 regulated miR-5008. Conclusion: Our results demonstrated that differentially expressed circRNAs (circ_0062019 and circ_0057558) and host gene SLC19A1 of circ_0062019 could be used as potential novel biomarkers for prostate cancer.

No abstract

No abstract

1000, 1100 and 1150°C isothermal sections of the Ti-Al-Nb system were studied using x-ray diffraction, scanning electron microscopy and electron probe microanalysis. A small island-like region of single b 0 is present at 1000, but absent at 1100 and 1150°C. c 1 is not a stable phase at 1000 and 1150°C. Three three-phase fields (a 2 ? b 0 ? r, b 0 ? r ? c and a 2 ? b 0 ? c) are identified in the 1000°C isothermal section (30-60 at.% Ti content). The 1100°C isothermal section is firstly studied completely. It includes six three-phase and thirteen two-phase fields. Two three-phase fields b ? a 2 ? c and b ? r ? c are identified in the isothermal section (30-60 at.% Ti content) at 1150°C. These data are helpful to the fabrication of the TiAl and Ti 2 AlNb intermetallics. Keywords intermetallics Á microstructure Á phase diagram Á TiAl alloy Dedicate to the celebration of Prof. Zhanpeng Jin's 80th birthday. This invited article is part of a special issue of the Journal of Phase Equilibria and Diffusion in honor of Prof. Zhanpeng Jin's 80th birthday. The special issue was organized by Prof. Ji-Cheng (JC) Zhao,