Hepatocellular carcinoma (HCC), one of the most common tumors worldwide, has the fifth highest mortality rate, which is increasing every year. At present, many studies have revealed that immunotherapy has an important effect on many malignant tumors. The main purpose of our research was to verify and establish a new immune-related lncRNA model and to explore the potential immune mechanisms. We analysed the pathways and mechanisms of immune-related lncRNAs by bioinformatics analysis, screened key lncRNAs based on Cox regression analysis, and determined the characteristics of the immune-related lncRNAs. On this basis, a predictive model was established. Through a comparison of specificity and sensitivity, we found that the constructed model was superior to the known markers of HCC. Then, the cell types were identified by the relative subgroup (CIBERSORT) algorithm for RNA transcripts. A signature model was eventually constructed, and we proved that it was a survival factor for HCC. Moreover, five kinds of immune cells were significantly positively correlated with the signature. The results indicated that these five kinds of lncRNAs may be related to the immune infiltration of hepatocellular carcinoma. To verify these findings, we selected the top coexpressed lncRNA, AC099850.3, for further study. We found that AC099850.3 could promote the migration and proliferation of hepatocellular carcinoma cells in vitro. RT-PCR experiments found that AC099850.3 could promote the expression of the cell cycle molecules BUB1, CDK1, PLK1, and TTK, and western blotting to prove that the expression of the molecules CD155 and PD-L1 was inhibited in the interference group. In conclusion, we used five kinds of immune-related lncRNAs to construct prognostic signatures to explore the mechanism, which provides a new way to study therapies for HCC.
Background Till now, no experiment has been performed to detect programmed death ligand 1 (PD-L1)/programmed death 1 (PD-1), soluble PD-L1/soluble PD-1 simultaneously in perioperative patients of gastric carcinoma. Our experiment aims at determining the clinical significance and possible mechanism of soluble PD-L1/soluble PD-1 in gastric carcinoma. Methods Thirty patients undergone gastrectomy were selected as the experimental group. Tissue’s programmed death ligand 1 and peripheral programmed death 1 were detected using immunofluorescence and flow cytometry. Soluble PD-L1 and soluble PD-1 were detected using enzyme-linked immunosorbent assay. Results First, preoperative programmed death 1 was higher than control group and decreased to normal post-operatively. Preoperatively ,elevated levels of programmed death 1 on cluster of differentiation (CD)4 T cells indicated less lymphatic metastasis (P < 0.01) and small tumor volume (P < 0.01); elevated programmed death 1 of CD8 T cells indicated big tumor volume (P < 0.01) and well histological differentiation (P < 0.01). Second, preoperative soluble PD-L1 and soluble PD-1 are lower than in control group. Post-operatively, the soluble PD-1 rose to normal, but the soluble PD-L1 showed no change. Third, programmed death ligand 1 can be observed in carcinoma tissue. Fourth, the area under the curve of soluble PD-1 (0.675) for diagnosis was worse than that of soluble PD-L1 (0.885). Kaplan-Meier analysis showed that soluble PD-1 < 245.26 pg/ml in post-operative serum predicted a poor prognosis (overall survival percentage: 60%) at 2 years (P < 0.05). Multivariate analysis revealed that carcinoembryonic antigen (>5 ng/l) and soluble PD-1 after gastrectomy (>245.26 pg/ml) were independent prognostic factors for overall survival (hazard ratio: 20.812, 95% confidence interval: 1.217–355.916, P = 0.036; hazard ratio: 0.028, 95% confidence interval: 0.001–0.786, P = 0.036, respectively). Conclusions We propose that soluble PD-1 combined with programmed death ligand 1 are effective not only in protecting T cells from the adhesion by programmed death ligand 1 but also in preventing the occurrence and the development of tumor as well. Through multivariate analysis, we found that soluble PD-1 was an independent protective factor for post-operative prognosis of gastric carcinoma patients, which indirectly verified the vital function of soluble PD-1. Soluble PD-1 might be promising predictive biomarkers for the diagnosis and prognosis of gastric carcinoma patients.
Tumour cells change their metabolic patterns to support high proliferation rates and cope with oxidative stress. The lncRNA ELFN1-AS1 is highly expressed in a wide range of cancers and is essential to the proliferation and apoptosis of tumour cells. Nevertheless, its function in the metabolic reprogramming of tumour cells is unclear. Here we show that ELFN1-AS1 promotes glucose consumption as well as lactate and NADPH production. Database searching, bioinformatics analysis, RNA immunoprecipitation (RIP) and RNA pull-down assays show that ELFN1-AS1 enhances glucose-6-phosphate dehydrogenase ( G6PD ) expression and activates the pentose phosphate pathway (PPP) by promoting TP53 degradation. In addition, luciferase reporter assay and chromatin immunoprecipitation (ChIP) show that YY1 binds to the ELFN1-AS1 promoter to promote transcriptional activation of ELFN1-AS1 . Consistent with the in vitro experiments, knockdown of ELFN1-AS1 impedes the growth of tumours transplanted into mice by inhibiting the expression of G6PD . In conclusion, this study reveals that ELFN1-AS1 activates the PPP, and validates the regulatory role of the YY1 / ELFN1-AS1 / TP53 / G6PD axis in colorectal cancer.
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