A novel algorithm for lung adenocarcinoma based on N6 methyladenosine-related immune long noncoding RNAs as a reliable biomarker for predicting survival outcomes and selecting sensitive anti-tumor therapies.

BACKGROUND: Lung cancer is a highly heterogeneous malignant tumor with high incidence and mortality. Recently, increasing evidence has demonstrated that N6-methyladenosine (m6A) methylation and the tumor microenvironment (TME) play important roles in the occurrence and development of lung adenocarcinoma (LUAD). METHODS: In this study, we constructed a novel and reliable algorithm based on m6A-related immune lncRNAs (mrilncRNAs), consisting of molecular subtypes and a prognostic signature. RESULTS: According to the analyses of molecular subtypes, patients in cluster 1 were in a more advanced stage, showed poor prognosis, were sensitive to immunotherapy (anti-programmed cell death 1 Ligand 1 (PD-L1) and anti-lymphocyte activating 3 (LAG-3)), and had a highest tumor mutational burden (TMB), while anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapy seemed to be a good choice for patients in cluster 3. Subsequently, the results of the risk assessment model indicated that the low-risk patients exhibited a survival advantage, had an earlier stage, and showed a higher response to common anti-cancer drugs, including chemotherapy (Docetaxel, Paclitaxel), molecular targeted therapy (Erlotinib), and immunotherapy (anti-CTLA-4 therapy), while Gefitinib could be a good choice for patients with high-risk scores. CONCLUSION: In conclusion, the constructed algorithm exhibits promising practical prospects, and allows the selection of suitable and sensitive anti-cancer drugs, which could provide theoretical support to predict the survival outcomes of patients with LUAD.

The diagnostic value of has_circ_0006423 in non-small cell lung cancer and its role as a tumor suppressor gene that sponges miR-492.

The diagnosis and treatment of non-small cell lung cancer (NSCLC) are not ideal. We identified NSCLC-related has_circ_0006423 in database. qRT-PCR was used to measure expression levels of hsa_circ_0006423 and miR-492 in the plasma and tissue samples, and 3 NSCLC cell lines, respectively. We analyzed the relationship between expression levels of hsa_circ_0006423 and clinicopathological factors and miR-492 expression in plasma and tissue samples. Assess the diagnostic value of hsa_circ_0006423 and miR-492 in NSCLC. Cell function vitro experiment to explore the effect of has_circ_0006423 on NSCLC. We found has_circ_0006423 is lower expressed in NSCLC and miR-492 is opposite, has_circ_0006423 and miR-492 has diagnostic value in NSCLC. In A549 and NCI-H1299 cells, hsa_circ_0006423 inhibited the proliferation, migration, and invasion of NSCLC cells by sponging miR-492 and accelerating NSCLC cell apoptosis. This effect may be due to the combination of has_circ_0006423 and miR-492 affecting the progression of NSCLC.

Upregulation of hsa_circ_0000977 participates in esophageal squamous cancer progression by sponging miR-874-3p.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is one of the most common clinical malignancies of the digestive system, characterized by high mortality but not evident early symptoms. Molecular markers for diagnostic and outcome prediction are urgently needed. Circular RNAs might play essential roles in the progression of ESCC. METHODS: Hsa_circ_0000977 was identified using circRNA microarrays and qRT-PCR. The diagnostic value of hsa_circ_0000977 was calculated. We also examined in vitro cell functions in ECA109 and TE12 ESCC cells to determine the effect of hsa_circ_0000977. A dual-luciferase reporter vector validated the binding of hsa_circ_0000977 to miR-874-3p. RESULTS: The top 10 significantly upregulated circRNAs from microarray assays were hsa_circ_0000977, hsa_circ_0006220, hsa_circ_0043278, hsa_circ_0000691, hsa_circ_0000288, hsa_circ_0000367, hsa_circ_0021647, hsa_circ_0006440, hsa_circRNA_405571 and hsa_circRNA_100790, while the top 10 significantly downregulated circRNAs were hsa_circ_0008389, hsa_circ_0089763, hsa_circ_0089762, hsa_circ_0000102, hsa_circ_0001714, hsa_circ_0089761, hsa_circ_0007326, hsa_circ_0001549, hsa_circ_0005133 and hsa_circRNA_405965. Hsa_circ_0000977 was significantly upregulated in ESCC (p < 0.01) and had diagnostic value in ESCC. The hsa_circ_0000977 expression level was related to the pT stage and numbers of lymph nodes in ESCC patients. Elevated hsa_circ_0000977 promoted cell proliferation, migration and inhibited apoptosis in ESCC cells. Hsa_circ_0000977 might function as a micro-RNA sponge to competitively bind miR-874-3p. CONCLUSION: Disordered hsa_circ_0000977 expression can promote carcinogenesis in ESCC and might serve as a diagnostic biomarker to evaluate the occurrence and development of esophageal cancer.

Hsa_circ_0000437 upregulates and promotes disease progression in rheumatic valvular heart disease.

BACKGROUND: Currently, the diagnosis and outcome of rheumatic valvular heart disease (RVHD) are less than ideal, and there are no accurate biomarkers. Circular RNA (circRNA) might participate in the occurrence and development of RVHD. MATERIALS AND METHODS: We use circRNA microarray to filter out the target has_circ_0000437. qRT-PCR was used to measure the expression levels of hsa_circ_0000437 in RVHD plasma samples. We assessed the diagnostic value of hsa_circ_0000437 in RVHD. Cell function in vitro experiment was to explore the effect of has_circ_0000437 on RVHD. RESULTS: Has_circ_0000437 is highly expressed in RVHD (p < 0.001). has_circ_0000437 has the diagnostic value in RVHD. In RVHD, hsa_circ_0000437 can promote cell proliferation and migration but inhibits its apoptosis. This may be due to the combination of has_circ_0000437 and target miRNA in the cytoplasm that affects the progress of RVHD. CONCLUSIONS: Has_circ_0000437 can promote the process of RVHD and may be a potential for the diagnosis and treatment of RVHD.

[The risk of esophageal squamous cell carcinoma associated with microsatellite polymorphism in promoter of heme oxygenase-1].

OBJECTIVE: To investigate the relationship between (GT)n polymorphism and esophageal cancer by analyzing the connection between microsatellite polymorphisms in the promoter of heme oxygenase-1 and the clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) in Han chinese population. METHODS: The (GT)n repeats in HO-1 gene in 83 male and 43 female hospital-based patients with ESCC (aged between 40 and 79 years with a mean of (61 ± 8) years) and 134 healthy control individuals were obtained by DNA sequencing. Polymorphisms of the (GT)n repeats were generally grouped into three classes based on allele frequencies: class S alleles (<25 repeats), class M alleles (25 to 29 repeats), and class L alleles (≥30 repeats). The correlation between susceptibility and clinicopathological characteristics of ESCC were analyzed by χ2 test. For in vitro experiments, the transient-transfection assay was performed to explore the correlation between different lengths of (GT)n repeats and promoter activity by assessing the promoter activities of HO-1 gene in cultured Ecal09 cells treated with H2O2 by analysis of cariance. RESULTS: Higher frequencies of L-allele (25. 8% vs. 14. 9%, χ2 = 9. 520, P = 0. 002), L-allele carrier (41. 3% vs. 27. 6%, χ2 = 5. 381 , P = 0. 020) were found in patients with ESCC. Furthermore, the lymphatic metastasis rate (63. 5% vs. 41. 8%, χ = 5. 685, P = 0. 017) and the detection rate of poorly differentiated ESCC cell (53. 8% vs. 28. 4%, χ2 = 8. 335, P = 0. 004) was significantly higher in L-allele carriers compared to non-L-allele carriers. In transfection experiments, promoter activities of 5'-flanking regions of the HO-1 gene in Eca109 cells transfected with the recombinant gene carrying (GT)16 repeat after treatment with H2O2 increased (F = 23. 615,P = 0. 008). In H2O treated control group, compared to (GT)26 and (GT)36, the basal promoter activities of HO-1 gene carrying (GT)16 repeat increased (F =41. 376, P = 0. 003; F = 50. 761, P = 0. 002). CONCLUSION: The long (GT)n repeats of HO-1 gene promoter can increase the susceptibility of esophageal squamous cell carcinoma and the risk of lymphatic metastasis.

[Effects of recombinant human erythropoietin on angiogenesis in chronic ischemic porcine myocardium].

OBJECTIVE: To investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) on angiogenesis in chronic ischemic porcine myocardium. METHODS: A ameroid constrictor was placed around the proximal circumflex branch of the left coronary artery in 12 Bama miniatures' swine artery by thoracoscopy. Electrocardiogram and coronary angiography were used to confirm the establishment of myocardial ischemia. The animals were divided into rhEPO treatment group (n = 6) and negative control group (n = 6). Treatment group received subcutaneous injection of rhEPO at 1, 3, 7, 14, 21 days, control group received saline. The expression of vascular endothelial growth factor (VEGF) in serum was assessed by ELISA. Ultrasonography and coronary angiography were assessed 28 days after therapy. Western blot was used to detect the expression of VEGF, phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal regulated kinases (p-Erk). The degree of angiogenesis was assessed by immunohistochemical analysis. RESULTS: Serum VEGF rose significantly in both control and treatment groups, peaking at 3 days and then returning to the near-baseline level at 28 days, but the two groups showed no significant difference at each time point (P > 0.05). Echocardiographic measurements showed that the left ventricular systolic function of animals in treatment group increase significantly after rhEPO therapy. the expression levels of VEGF, p-Akt and p-Erk had markedly increased, which resulted in a 2.5-fold increased of VEGF, 1.1-fold increased of p-Akt, 1.5-fold increased of p-Erk (t = 37.721, 10.907, 12.957, all P = 0.000). there were significant increase in capillary density and arteriole density in the two groups ((944 ± 98) %/mm² vs. (569 ± 102) %/mm², (73 ± 13) %/mm² vs. (45 ± 10) %/mm², t = 4.214, 2.869, P = 0.016, 0.023). CONCLUSIONS: rhEPO can promote angiogenesis and arteriogenesis and improve the left ventricular systolic function in porcine model of chronic myocardial ischemia. The potential mechanism is to up-regulated the expression of p-Akt and p-Erk.