Genome-wide RNA-sequencing dataset reveals AC096751.1 sever as a novel prognostic long non-coding RNA and its potential molecular mechanisms in patients with colon adenocarcinoma.

Objective: Through data analysis, we observed that AC096751.1 is markedly imbalance between colon adenocarcinoma (COAD) cancer and paracancerous tissues. However, the prognostic value and potential molecular mechanism of AC096751.1 in COAD are still unclear. Methods: Whole genome RNA-sequencing datasets of The Cancer Genome Atlas (TCGA) COAD cohort were collected into current study, comprehensive survival analysis and bioinformatics function enrichment analysis approaches were apply to explore the clinical outcome and molecular mechanisms of AC096751.1 in COAD. Results: In current study, we found that AC096751.1 is markedly down-regulated in COAD cancer tissues (log2 fold change =2.303, P<0.0001, false discovery rate <0.0001), and can be serve as a biomarker to distinguish COAD cancer and paracancerous tissues [area under curve=0.9518, 95% confidence interval (CI)=0.9261-0.9776]. Survival analysis suggests that low expression of AC096751.1 is connected with poor clinical outcome of COAD, and can serve as a novel prognostic indicator (log-rank P=0.016, adjusted P=0.005, hazard ratio=0.548, 95% CI=0.360-0.836). Bioinformatics function enrichment analysis suggests that the molecular mechanism of AC096751.1 in COAD may include participation in cell adhesion, cell proliferation, mitogen-activated protein kinase kinase (MAPKK), MAPK, janus-activated kinase-singal transducers and activators of transcriprion cascade, Erk1 and Erk 2 cascade, and nuclear factor-kappa B pathway. Tumor microenvironment and immune infiltration analysis indicates that COAD patients with different AC096751.1 expression have significant variation in tumor immune background. Conclusion: The present study found that AC096751.1 is significantly differentially expressed in COAD and can be serve as a novel prognostic biomarker.

Aberrant LYZ expression in tumor cells serves as the potential biomarker and target for HCC and promotes tumor progression via csGRP78.

Hepatocellular carcinoma (HCC) takes the predominant malignancy of hepatocytes with bleak outcomes owing to high heterogeneity among patients. Personalized treatments based on molecular profiles will better improve patients' prognosis. Lysozyme (LYZ), a secretory protein with antibacterial function generally expressed in monocytes/macrophages, has been observed for the prognostic implications in different types of tumors. However, studies about the explicit applicative scenarios and mechanisms for tumor progression are still quite limited, especially for HCC. Here, based on the proteomic molecular classification data of early-stage HCC, we revealed that the LYZ level was elevated significantly in the most malignant HCC subtype and could serve as an independent prognostic predictor for HCC patients. Molecular profiles of LYZ-high HCCs were typical of those for the most malignant HCC subtype, with impaired metabolism, along with promoted proliferation and metastasis characteristics. Further studies demonstrated that LYZ tended to be aberrantly expressed in poorly differentiated HCC cells, which was regulated by STAT3 activation. LYZ promoted HCC proliferation and migration in both autocrine and paracrine manners independent of the muramidase activity through the activation of downstream protumoral signaling pathways via cell surface GRP78. Subcutaneous and orthotopic xenograft tumor models indicated that targeting LYZ inhibited HCC growth markedly in NOD/SCID mice. These results propose LYZ as a prognostic biomarker and therapeutic target for the subclass of HCC with an aggressive phenotype.

Correlation Between Serum High-Sensitivity C-Reactive Protein, Tumor Necrosis Factor-Alpha, Serum Interleukin-6 and White Matter Integrity Before and After the Treatment of Drug-Naïve Patients With Major Depressive Disorder.

Background: Previous studies have noticed that systemic inflammation may alter the integrity of white matter. However, how the levels of serum cytokine affect the integrity of white matter in major depressive disorder (MDD) patients are unclear. Our study aimed to investigate the association between the inflammatory cytokine levels and white matter microstructure in drug-naïve patients with MDD pre- and post-treatment. Method: In total, 29 MDD patients and 25 healthy controls (HC) were included in this study. Diffusion tensor imaging (DTI) was conducted in all subjects at baseline, and the MDD patients were reassessed after venlafaxine treatment, using a tract-based spatial statistics (TBSS) analysis. Morning serum interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) concentrations in MDD patients were also measured pre- and post-treatment. Results: Significantly reduced fractional anisotropy (FA) values were found in the bilateral superior fronto-occipital fasciculus (SFO), posterior limb of the internal capsule (IC-PL), and fornix compared with the HC, and FA values in these regions in MDD patients have risen to normal levels except the bilateral SFO after treatment. The FA value of the left IC-PL was inversely correlated with the peripheral hs-CRP levels in both pre- and post-treatment MDD patients. Conclusion: Our results suggested that the white matter integrity in the left IC-PL was significantly inversely correlated with the peripheral hs-CRP levels in both pre- and post-treatment MDD patients.

USP19 suppresses cellular type I interferon signaling by targeting TRAF3 for deubiquitination.

AIM: To investigate host factors that mediate the immune escape of enterovirus 71 (EV71) in the context of deubiquitinating enzymes. MATERIALS & METHODS: Utilize PCR array to screen candidate genes that may be involved in EV71-induced cellular antiviral immune responses, and utilize protein mass spectrometry analysis to identify the functional targets of the candidate regulator. RESULTS: EV71 infection induces the upregulation of ubiquitin-specific protease 19 (USP19) gene expression, which negatively regulates cellular antiviral type I interferon signaling. Additionally, we identify that USP19 suppresses cellular type I interferon signaling by targeting tumor necrosis factor receptor-associated factor 3 (TRAF3) molecule and decreasing TRAF3 ubiquitination of K63-linkage. CONCLUSION: This work suggests that USP19 is a previously unrecognized regulator employed by EV71 to evade host antiviral defenses.

Resveratrol inhibits enterovirus 71 replication and pro-inflammatory cytokine secretion in rhabdosarcoma cells through blocking IKKs/NF-κB signaling pathway.

Polydatin and resveratrol, as major active components in Polygonum cuspidatum, have anti-inflammatory, antioxidant and antitumor functions. However, the effect and mechanism of polydatin and resveratrol on enterovirus 71 (EV71) have not been reported. In this study, resveratrol revealed strong antiviral activity on EV71, while polydatin had weak effect. Neither polydatin nor resveratrol exhibited influence on viral attachment. Resveratrol could effectively inhibit the synthesis of EV71/VP1 and the phosphorylation of IKKα, IKKß, IKKγ, IKBα, NF-κB p50 and NF-κB p65, respectively. Meanwhile, the remarkably increased secretion of IL-6 and TNF-α in EV71-infected rhabdosarcoma (RD) cells could be blocked by resveratrol. These results demonstrated that resveratrol inhibited EV71 replication and cytokine secretion in EV71-infected RD cells through blocking IKKs/NF-κB signaling pathway. Thus, resveratrol may have potent antiviral effect on EV71 infection.