Three Circulating Long Non-Coding RNAs Act as Biomarkers for Predicting NSCLC

Background/Aims: Circulating long non coding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and as potential therapeutic targets. We explored circulating lncRNA as a predictor for the tumorigenesis of non-small-cell lung cancer (NSCLC). Methods: In this study, we applied a lncRNA microarray to screen for a potential biomarker for NSCLC, utilizing RT-PCR (ABI 7900HT). A multi-stage validation and risk score formula detection analysis was used. Results: We discovered that three lncRNAs (RP11-397D12.4, AC007403.1, and ERICH1-AS1) were up regulated in NSCLC, compared with cancer-free controls, with the merged area under the curve in the training and validation sets of 0.986 and 0.861. Furthermore, the positive predictive value and negative predictive value of the three merged factors were 0.72 and 0.87. We confirmed stable detection of the three lncRNAs by three cycles of freezing and thawing. Conclusions: RP11-397D12.4, AC007403.1, and ERICH1-AS1 may be potential biomarkers for predicting the tumorigenesis of NSCLC in the future

Dachengqi Decoction Attenuates Inflammatory Response via Inhibiting HMGB1 Mediated NF-κB and P38 MAPK Signaling Pathways in Severe Acute Pancreatitis

Background/Aims: Severe acute pancreatitis (SAP) is a sudden inflammation of the pancreas. The traditional Chinese medicine formula Dachengqi decoction (DCQD) is proven to be beneficial in the comprehensive treatment for pancreatitis patients in clinical practice. However, the molecular mechanism of DCQD on SAP remains unclear. High mobility group box 1(HMGB1) that functions as a damage-associated molecular pattern molecule (DAMP) has attracted much interest. Methods: In this study, we used lipopolysaccharide (LPS) and cerulein to induce severe acute pancreatitis in C57BL/6 mice with subsequent administration with low, medium and high dose (2.3 g/kg, 7 g/kg and 21 g/kg, respectively) of DCQD. Results: DCQD treatment improved the pathological score and decreased serum amylase and lipase in a dose-dependent manner. In addition, it suppressed the immune cell-induced secretion of HMGB1 and its translocation from the nucleus to the cytoplasm, thus repressing the expression of IL-6 and TNF-α. Further, pretreatment with DCQD decreased responses of TLRs, and suppressed the activation of NF-kB and p38 MAPK pathway. Conclusion: Decreasing the secretion of HMGB1 could reduce pro-inflammatory cytokines, which may help cutting down the risks of development from localized pathological changes to a systemic inflammatory response syndrome and even lead to multiple organ failure

circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity

Circular RNAs (circRNA) is a class of non-coding RNAs that can regulate gene translation and function. Here the authors show that a circRNA, circNDUFB2, is downregulated in non-small cell lung cancer tissues, and likely contributes to anti-tumor immunity by regulating both degradation of oncoproteins and induction of innate immunity

Loss of hepatic FTCD promotes lipid accumulation and hepatocarcinogenesis by upregulating PPARγ and SREBP2

Background & Aims: Exploiting key regulators responsible for hepatocarcinogenesis is of great importance for the prevention and treatment of hepatocellular carcinoma (HCC). However, the key players contributing to hepatocarcinogenesis remain poorly understood. We explored the molecular mechanisms underlying the carcinogenesis and progression of HCC for the development of potential new therapeutic targets. Methods: The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) and Genotype-Tissue Expression (GTEx) databases were used to identify genes with enhanced expression in the liver associated with HCC progression. A murine liver-specific Ftcd knockout (Ftcd-LKO) model was generated to investigate the role of formimidoyltransferase cyclodeaminase (FTCD) in HCC. Multi-omics analysis of transcriptomics, metabolomics, and proteomics data were applied to further analyse the molecular effects of FTCD expression on hepatocarcinogenesis. Functional and biochemical studies were performed to determine the significance of loss of FTCD expression and the therapeutic potential of Akt inhibitors in FTCD-deficient cancer cells. Results: FTCD is highly expressed in the liver but significantly downregulated in HCC. Patients with HCC and low levels of FTCD exhibited worse prognosis, and patients with liver cirrhosis and low FTCD levels exhibited a notable higher probability of developing HCC. Hepatocyte-specific knockout of FTCD promoted both chronic diethylnitrosamine-induced and spontaneous hepatocarcinogenesis in mice. Multi-omics analysis showed that loss of FTCD affected fatty acid and cholesterol metabolism in hepatocarcinogenesis. Mechanistically, loss of FTCD upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element–binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis. Conclusions: Taken together, we identified a FTCD-regulated lipid metabolic mechanism involving PPARγ and SREBP2 signaling in hepatocarcinogenesis and provide a rationale for therapeutically targeting of HCC driven by downregulation of FTCD. Impact and implications: Exploiting key molecules responsible for hepatocarcinogenesis is significant for the prevention and treatment of HCC. Herein, we identified formimidoyltransferase cyclodeaminase (FTCD) as the top enhanced gene, which could serve as a predictive and prognostic marker for patients with HCC. We generated and characterised the first Ftcd liver-specific knockout murine model. We found loss of FTCD expression upregulated peroxisome proliferator-activated receptor (PPAR)γ and sterol regulatory element–binding protein 2 (SREBP2) by regulating the PTEN/Akt/mTOR signalling axis, leading to lipid accumulation and hepatocarcinogenesis, and provided a rationale for therapeutic targeting of HCC driven by downregulation of FTCD