Systemic analysis of the DNA replication regulator origin recognition complex in lung adenocarcinomas identifies prognostic and expression significance.

BACKGROUND: DNA replication alteration is a hallmark of patients with lung adenocarcinoma (LUAD) and is frequently observed in LUAD progression. Origin recognition complex (ORC) 1, ORC2, ORC3, ORC4, ORC5, and ORC6 form a replication-initiator complex to mediate DNA replication, which plays a key role in carcinogenesis, while their roles in LUAD remain poorly understood. METHODS: The mRNA and protein expression of ORCs was confirmed by the GEPIA, HPA, CPTAC, and TCGA databases. The protein-protein interaction network was analyzed by the GeneMANIA database. Functional enrichment was confirmed by the Metascape database. The effects of ORCs on immune infiltration were validated by the TIMER database. The prognostic significance of ORCs in LUAD was confirmed by the KM-plot and GENT2 databases. DNA alteration and protein structure were determined in the cBioProtal and PDB databases. Moreover, the protein expression and prognostic value of ORCs were confirmed in our LUAD data sets by immunohistochemistry (IHC) staining. RESULTS: ORC mRNA and protein were significantly increased in patients with LUAD compared with corresponding normal tissue samples. The results of IHC staining analysis were similar result to those of the above bioinformatics analysis. Furthermore, ORC1 and ORC6 had significant prognostic values for LUAD patients. Furthermore, the ORC cooperatively promoted LUAD development by driving DNA replication, cellular senescence, and metabolic processes. CONCLUSION: The ORC, especially ORC1/6, has important prognostic and expression significance for LUAD patients.

Significance of chromobox protein (CBX) expression in diffuse LBCL.

BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is the main pathological type of non-Hodgkin lymphoma (NHL). Chromobox (CBX) family proteins are classical components of polycomb group (PcG) complexes in many cancer types, resulting in accelerated carcinogenesis. Nevertheless, the prognostic, functional and expression significance of these CBX family members in DLBCL remain unclear and elusive. METHODS: CBX transcriptional levels were confirmed using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA) and Cancer Cell Line Encyclopedia (CCLE) databases. The protein levels of CBX family members were analysed using The Human Protein Atlas (HPA) database. Information on the PPI network, functional enrichment, drug sensitivity, prognostic value, miRNA network, protein structure, genetic alteration and immune cell infiltration were generated using the GeneMANIA, Metascape, GSCALite, GEPIA, PDB, cBioPortal, and TIMER databases, and the correlation of these factors with CBX expression levels in DLBCL was assessed. RESULTS: CBX1/2/3/5/6/8 mRNA levels were significantly enhanced in DLBCL tissues compared to corresponding normal tissues. CBX1/3/4/5/8 protein expression levels were obviously increased, whereas CBX7 was obviously decreased. This difference might be attributed to miRNA regulation based on the miRNA network. Overall survival (OS) analysis showed that CBX levels were not correlated with prognosis in DLBCL patients, indicating that CBXs are not good biomarkers for DLBCL patients. Furthermore, functional enrichment analyses indicated that CBXs were closely related to DNA duplex unwinding, covalent chromatin modification, and histone lysine methylation. The levels of CBXs were also significantly associated with diverse immune cell infiltration in DLBCL. CONCLUSIONS: This study reveals that dysregulated CBXs are involved in DLBCL development and might represent potential therapeutic targets for DLBCL.

Circular RNA circEPSTI1 accelerates cervical cancer progression via miR-375/409-3P/515-5p-SLC7A11 axis.

BACKGROUND: Circular RNAs (circRNAs) is one kind of non-coding RNAs (ncRNAs) and exert crucial functions in biological processes and intracellular gene expression modulation. However, the biological roles and expression status of the majority of circRNAs still remain unknown in cervical cancer. RESULTS: In this study, circEPSTI1 (hsa_circRNA_000479) was significantly upregulated in cervical cancer. We first discovered the impact of circRNA on cell ferroptosis in cervical cancer. Interestingly, circEPSTI1 attenuates the effect of ferritin which is mediated by SLC7A11 based on lipid peroxidation measurements and reduced glutathione and glutathione (GSH/GSSG) assay. CONCLUSIONS: circEPSTI1-miR-375/409-3P/515-5p-SLC7A11 axis affected the proliferation of cervical cancer via the competing endogenous RNAs (ceRNA) mechanism and was relative to ferroptosis. Our findings provided experimental evidences which revealed that circEPSTI1 might act as a new and useful biomarker for monitoring and treatment target for cervical cancer. METHODS: The expression of circEPSTI1 was examined in cervical cancer cells. Then, we observed the impact of circEPSTI1 expression on the proliferation of cervical cancer by loss-of-function assays both in vivo and vitro. RIP and luciferase reporter assay revealed that circEPSTI1 sponges miR-375, miR-409-3p and miR-515-5p to upregulate SLC7A11 expression. We applied mouse xenograft experiments in mice to validate our results.

Significant function and research progress of biomarkers in gastric cancer.

Gastric cancer is one of the most common gastrointestinal tumor types, and the incidence and mortality rates are higher in men compared with women. Various studies have revealed that gastric cancer is a spectrum of tumor types, which have biological and genetic diversity. It has proven to be difficult to improve the overall survival and disease-free survival of patients with gastric cancer through the use of traditional surgery and chemoradiation, as gastric cancer is usually identified at an advanced stage. In consequence, the outcome is frequently poor. Thus, novel biomarkers and anticancer targets are required to improve the outcome. As the identification of biomarkers has increased due to advances in research and the greater availability of bioinformatics and functional genomics, the potential therapeutic regimens available have also increased concurrently. These advances have also improved the ability to predict responses to chemotherapy, targeted therapy and immunotherapy, whilst other biomarkers predict post-treatment survival and recurrence based on their expression. This review focuses closely on the important functions of biomarkers in the timely diagnosis and treatment of gastric cancer, in addition to the advances in the study of certain novel markers in gastric cancer.

Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) in non-small cell lung cancer.

Nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2) is a transcription factor that can regulate downstream target gene expression. Kelch-like ECH-associated protein 1 (Keap1) negatively regulates Nrf2 activation and translocation to target its 26S proteasomal degradation. It has been widely reported that the Keap1/Nrf2 pathway is associated with tumorigenesis, chemotherapy resistance and progression and development of non-small cell lung cancer (NSCLC). High expression of Nrf2 and low abundance of Keap1 contribute to the abnormalities and unrealistic treatment prognosis of NSCLC. Therefore, elucidating the role and potential mechanism of Nrf2 in NSCLC is essential for understanding tumorigenesis and for the development of strategies for effective clinical management. Here, we summarize current knowledge about the molecular structure and biological function of Nrf2, and we discuss the roles of Nrf2 in tumorigenesis, which will further provide a possible therapeutic strategy for NSCLC.

Human p21-activated kinase 5 (PAK5) expression and potential mechanisms in relevant cancers: Basic and clinical perspectives for molecular cancer therapeutics.

An oncogenic role, p21-activated kinase 5 (PAK5), has proven as a significant mediator for many cellular progression, which is expressed highly in human organs such as lung, liver, kidney, blood vessels endothelial cells and inflammatory cells. PAK5 was primitively detected in the cerebrum and accelerated the filopodia formation in neurocytes. It can reverse the effect of Rho and adjust its activity to mediate maintenance and development of nerve axon by binding with Cdc42-GTP. Moreover, PAK5 has been suggested to mediate protean, multitudinous and inscrutable functions in cancer. Currently, many researches indicated that PAK5 was dysregulated in ovarian cancer, cervical cancer, melanoma, osteosarcoma, renal carcinoma, breast cancer, gastric cancer and so on, which was involved in cell proliferation, apoptosis, migration and invasion. This review focuses the latest knowledge on the structure, expression, signalling pathway of PAK5, emphasizing its function in cancer.

[Influencing factors and evaluation indicators for asthma control level in children].

OBJECTIVE: To investigate the influencing factors for asthma control level in children and the practicability of evaluation indicators for asthma. METHODS: A total of 185 children with asthma were enrolled. Questionnaires and pulmonary function test were used to evaluate the asthma control level and the factors influencing the control level. The correlation between evaluation indicators and asthma control level was analyzed. RESULTS: Among the 185 children with asthma, 139 (75.1%) achieved full control, 36 (19.5%) achieved partial control, and 10 (5.4%) had uncontrolled asthma. Application of inhaled corticosteroids and eosinophil count showed significant effects on asthma control level (P<0.05). There were significant differences in the percentage of forced expiratory volume in 1 second (FEV1%), fractional exhaled nitric oxide (FeNO), childhood asthma control test (C-ACT) questionnaire score, and pediatric asthma quality of life questionnaire (PAQLQ) score between the full control, partial control, and uncontrolled groups (P<0.05). In the children with asthma, FEV1% was positively correlated with C-ACT and PAQLQ scores (P<0.05), while there was no significant correlation between FEV1% and FeNO (P=0.214). CONCLUSIONS: Application of inhaled corticosteroids and eosinophil count are factors influencing asthma control in children. A combination of FEV1%, FeNO, C-ACT score, and PAQLQ score helps with the evaluation of asthma control level.

Characteristics of deslanoside-induced modulation on jejunal contractility.

AIM: To characterize the dual effects of deslanoside on the contractility of jejunal smooth muscle. METHODS: Eight pairs of different low and high contractile states of isolated jejunal smooth muscle fragment (JSMF) were established. Contractile amplitude of JSMF in different low and high contractile states was selected to determine the effects of deslanoside, and Western blotting analysis was performed to measure the effects of deslanoside on myosin phosphorylation of jejunal smooth muscle. RESULTS: Stimulatory effects on the contractility of JSMF were induced (45.3% ± 4.0% vs 87.0% ± 7.8%, P < 0.01) by deslanoside in 8 low contractile states, and inhibitory effects were induced (180.6% ± 17.8% vs 109.9% ± 10.8%, P < 0.01) on the contractility of JSMF in 8 high contractile states. The effect of deslanoside on the phosphorylation of myosin light chain of JSMF in low (78.1% ± 4.1% vs 96.0% ± 8.1%, P < 0.01) and high contractile state (139.2% ± 8.5% vs 105.5 ± 7.34, P < 0.01) was also bidirectional. Bidirectional regulation (BR) was abolished in the presence of tetrodotoxin. Deslanoside did not affect jejunal contractility pretreated with the Ca(2+) channel blocker verapamil or in a Ca(2+)-free assay condition. The stimulatory effect of deslanoside on JSMF in a low contractile state (low Ca(2+) induced) was abolished by atropine. The inhibitory effect of deslanoside on jejunal contractility in a high contractile state (high Ca(2+) induced) was blocked by phentolamine, propranolol and L-NG-nitro-arginine, respectively. CONCLUSION: Deslanoside-induced BR is Ca(2+) dependent and is related to cholinergic and adrenergic systems when JSMF is in low or high contractile states.