The rapid production and release of a large number of inflammatory cytokines can cause excessive local and systemic inflammation in severe acute pancreatitis (SAP) and multiple organ dysfunction syndrome (MODS), especially pancreatitis-associated acute lung injury (P-ALI), which is the main cause of early death in patients with SAP. The NLRP3 inflammasome plays an important role in the maturation of IL-1β and the inflammatory cascade. Here, we established a model of SAP using wild-type (NLRP3^+/+) and NLRP3 knockout (NLRP3^-/-) mice by intraperitoneal injections of caerulein (Cae) and lipopolysaccharide (LPS). Pathological injury to the pancreas and lungs, the inflammatory response, and neutrophil infiltration were significantly mitigated in NLRP3^-/- mice. Furthermore, INF-39, an NLRP3 inflammasome inhibitor, could reduce the severity of SAP and P-ALI in a dose-dependent manner. Our results suggested that SAP and P-ALI were alleviated by NLRP3 deficiency in mice, and thus, reducing NLRP3 expression may mitigate SAP-associated inflammation and P-ALI.

Purpose: Circular RNAs (circRNAs) play important roles in the development and progression of various human cancers. hsa-circ-0046600 is a circRNA of unknown function. The purpose of this study was to investigate the biological function of hsa-circ-0046600 in hepatocellular carcinoma (HCC) and elucidate the possible molecular mechanisms of this circRNA. Materials and methods: GSE97332, quantitative reverse transcription polymerase chain reaction (qRT-PCR) and fluorescence in situ hybridization (FISH) were used to detect the expression of hsa-circ-0046600 in HCC tissues and cells. A dual-luciferase reporter assay was used to confirm the interaction between hsa-circ-0046600 and miR-640, and a meta-analysis confirmed the expression of miR-640 in HCC. Bioinformatics was used for the functional analysis of miR-640 target genes. N-cadherin and HIF-1α expression was measured by Western blot analysis. Results: The expression level of hsa-circ-0046600 in HCC tissue was significantly higher than that in adjacent normal tissue (P < 0.05) and was associated with tumour size, TNM stage and pathological vascular invasion. Moreover, the downregulated expression of hsa-circ-0046600 significantly inhibited the migration of HepG2 and SK-HEP-1 cells. hsa-circ-0046600 is present mainly in the cytoplasm and promotes the expression of proteins such as HIF-1α by competitively binding to miR-640 in HCC, thereby affecting the malignant biological behaviour of liver cancer cells. Conclusion: hsa-circ-0046600 can be used as a new biomarker for HCC diagnosis and disease progression and provides a potential target for targeted therapy.

MiR-29a up-regulation in AR42J cells contributes to apoptosis via targeting TNFRSF1A gene

Background: Accumulating studies have demonstrated that the Warburg effect plays a central role in the occurrence and development of hepatocellular carcinoma (HCC), albeit the role of non-coding RNA (lncRNA) in its association remains unclear. Methods: The Zhengzhou University People’s Hospital kindly provided 80 pairs of HCC tissues and their matched paracancerous tissues for this study. Bioinformatics analysis, real-time quantitative polymerase chain reaction, Western blotting, and oncology functional assays were performed to determine the contribution of RP11-620J15.3 to the development of HCC. The mechanism of co-immunoprecipitation and a luciferase reporter gene was employed to ascertain how RP11-620J15.3 interacts with important molecular targets. Results: Our results revealed that a lncRNA termed RP11-620J15.3 was overexpressed in HCC and was substantially associated with the tumor size. A high expression of RP11-620J15.3 mRNA was found to be significantly associated with worsening prognosis in HCC patients. We discovered that RP11-620J15.3 stimulated the glycolytic pathway in HCC cells by RNA-sequencing (RNA-seq) and metabolomics analyses. Mechanistically, RP11-620J15.3 acted as a competitive endogenous RNA to regulate the GPI expression by sponging miR-326 in HCC. In addition, TBP acted as a transcription factor for RP11-620J15.3, which contributed to the high expression of RP11-620J15.3 in HCC cells. Conclusion: Based on our findings, lncRNA RP11-620J15.3 is a novel LncRNA that positively regulates tumor progression. Specifically, RP11-620J15.3/miR-326/GPI pathway promotes HCC malignant progression by regulating glycolysis, thereby providing novel targets for HCC treatment and drug development.