Hepatocellular carcinoma (HCC) is a major challenge for human health. Finding reliable diagnostic biomarkers and therapeutic targets for HCC is highly desired in the clinic. Currently, circulating exosomal lncRNA is a promising biomarker for the diagnosis of cancer and lncRNA is also a potential target in cancer therapy. Here, the diagnostic value of a panel based on exosomal lncRNA THEMIS2‐211 and PRKACA‐202, superior to that of AFP, was identified for diagnosing human HCC. Besides, the performance of exosomal lncRNA THEMIS2‐211 alone exceeds that of AFP in diagnosing early‐stage HCC patients (stage I). Furthermore, lncRNA THEMIS2‐211 is highly expressed in HCC tissues and correlated with the poor prognosis of HCC patients. LncRNA THEMIS2‐211 is upregulated and localized in the cytoplasm of HCC cells. LncRNA THEMIS2‐211 exerts its biological function as an oncogene that promotes the proliferation, migration, invasion, EMT of HCC cells by physically interacting with miR‐940 and therefore promoting SPOCK1 expressions. Rescue assays show the regulation of SPOCK1 by lncRNA THEMIS2‐211 dependents on miR‐940. The discovery of lncRNA THEMIS2‐211 further illuminates the molecular pathogenesis of HCC and the THEMIS2‐211/miR‐940/SPOCK1 axis may act as a potential therapeutic target for HCC.

Many type B polycyclic polyprenylated acylphloroglucinols (PPAPs) bear a lavandulyl-derived substituent, and the configurational assignment of this side chain can be difficult and sometimes leads to erroneous conclusions. In this study, 21 PPAPs, including the new xanthochymusones A–I (1–9), have been isolated from the fruits of Garcinia xanthochymus and structurally characterized. The relative configuration of the C-30 stereocenter was assigned by a combination of chemical transformations, 1H–1H coupling constants, conformational analysis, and NOE experiments. The configurational assignment of compound 7 indicates that the relative configuration at C-30 of PPAPs is not always the same. The absolute configurations of the new compounds were assigned by ECD and X-ray diffraction data, as well as by biosynthetic considerations. Analysis of NMR data enabled the configurational revision of garcicowins C and D. All the isolated PPAPs were tested for antiproliferative activity against three human hepatocellular carcinoma cell lines, including Huh-7, Hep 3B, and HepG2. Compounds 5 and 6, 7-epi-isogarcinol (16), and coccinone C (17) exhibited moderate antiproliferative activity. Compounds 6 and 16 induced apoptosis and inhibited cell migration in Huh-7 cells, probably through downregulating the STAT3 signaling pathway. This study provides effective methods for configurational assignments of type B PPAPs.

Colorectal cancer (CRC) is the second most lethal cancer and the third most common cancer in the world, and its prognosis is severely affected by high intestinal mucosal permeability and increasing tumor burden. Studies have shown that the expression of hypoxia induce factor 1α (HIF1α) is up-regulated in a variety of tumor tissues, which is related to multiple metabolic reprogramming of tumor cells. However, the role of HIF1α in CRC tumor growth, tumor polyamine metabolism and intestinal mucosal barrier damage has not been studied. Here, we constructed different types of CRC tumor-bearing mice models by inoculating HCT116 cells with different levels of HIF1α expression (knockdown, wild type, overexpression) in the armpits of mice to explore the upstream and downstream regulators of HIF1α, the effects of HIF1α on the growth of CRC, and the CRC polyamine metabolism and its effect on the intestinal mucosal barrier. We found that with the increase of HIF1 gene expression, tumor growth was promoted and intestinal mucosal permeability was increased. The expression of glycolysis-related proteins was up-regulated, the rate-limiting enzyme ODC of polyamine synthesis was decreased, and the transfer protein of polyamine was increased. HPLC showed that the polyamine content in the tumor tissue of the overexpression group HIF1α OE was higher than that of the wild group HIF1α (+/+), and higher than that of the knockdown group HIF1α (-/-), but the content of polyamines in intestinal mucosa was the opposite. After supplementation of exogenous polyamines, the content of polyamines in intestinal mucosa and tumor tissue increased, and the damage of intestinal mucosa was alleviated. In conclusion, upon activation of the MYC/HIF1 pathway, tumor glycolysis is enhanced, tumors require more energy and endogenous polyamine synthesis is reduced. Therefore, in order to meet its growth needs, tumor will rob polyamines in the intestinal mucosa, resulting in intestinal mucosal epithelial barrier dysfunction.

Background Hepatocellular carcinoma (HCC) as a common tumor has a poor prognosis. Recently, a combination of atezolizumab and bevacizumab has been recommended as the preferred regimen for advanced HCC. However, the overall response rate of this therapy is low. There is an urgent need to identify sensitive individuals for this precise therapy among HCC patients. Methods The Wilcox test was used to screen the differentially expressed immune-related genes by combining the TCGA cohort and the Immunology Database. Univariate and multivariate Cox regression analysis were used to screen the immune gene pairs concerning prognosis. A predictive model was constructed using LASSO Cox regression analysis, and correlation analysis was conducted between the signature and clinical characteristics. ICGC cohort and GSE14520 were applied for external validations of the predictive risk model. The relationship between immune cell infiltration, TMB, MSI, therapeutic sensitivity of immune checkpoint inhibitors, targeted drugs, and the risk model were assessed by bioinformatics analysis in HCC patients. Results A risk predictive model consisting of 3 immune-related gene pairs was constructed and the risk score was proved as an independent prognostic factor for HCC patients combining the TCGA cohort. This predictive model exhibited a positive correlation with tumor size (p < 0.01) and tumor stage (TNM) (p < 0.001) in the chi-square test. The predictive power was verified by external validations (ICGC and GSE14520). The risk score clearly correlated with immune cell infiltration, MSI, immune checkpoints, and markers of angiogenesis. Conclusions Our research established a risk predictive model based on 3 immune-related gene pairs and explored its relationship with immune characteristics, which might help to assess the prognosis and treatment sensitivity to immune and targeted therapy of HCC patients.

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