Neurotransmitters: Impressive regulators of tumor progression.

In contemporary times, tumors have emerged as the primary cause of mortality in the global population. Ongoing research has shed light on the significance of neurotransmitters in the regulation of tumors. It has been established that neurotransmitters play a pivotal role in tumor cell angiogenesis by triggering the transformation of stromal cells into tumor cells, modulating receptors on tumor stem cells, and even inducing immunosuppression. These actions ultimately foster the proliferation and metastasis of tumor cells. Several major neurotransmitters have been found to exert modulatory effects on tumor cells, including the ability to restrict emergency hematopoiesis and bind to receptors on the postsynaptic membrane, thereby inhibiting malignant progression. The abnormal secretion of neurotransmitters is closely associated with tumor progression, suggesting that focusing on neurotransmitters may yield unexpected breakthroughs in tumor therapy. This article presents an analysis and outlook on the potential of targeting neurotransmitters in tumor therapy.

Primary and Recurrent Intraosseous Adenoid Cystic Carcinoma-Analysis of Two Cases and Literature Review.

Adenoid cystic carcinoma (ACC) is a rare malignant tumor that mostly occurs in minor glands, especially in the palate. Intraosseous adenoid cystic carcinoma (IACC) is rarer. There is no clear conclusion on the clinical, radiologic and pathological characteristics of IACC because of few reported IACC cases, leading to insufficient understanding of IACC. We reviewed 52 previous reports of primary IACC (PIACC) and analyzed the clinical features of those patients involved, attempting to provide a better understanding of PIACC. Moreover, we present a case of primary PIACC and a case of recurrent IACC (RIACC). The two patients showed similarities in clinical and pathological results, along with slight differences in radiological and immunohistochemical results. The patient of case 1 seemed to display a worse prognosis, which can only be proved after long term follow-up.

Giant Mandibular Ameloblastoma with Rare Hypercalcemia: A Case Report and Literature Review.

Ameloblastoma is the most common benign odontogenic tumor with local invasion and high recurrence, which generally occurs in the jaw bones. Hypercalcemia is a common paraneoplastic syndrome that is commonly observed in patients with malignancies but rarely encountered in patients with benign tumors. Thus far, not many cases of ameloblastoma with hypercalcemia have been reported, and the pathogenic mechanism has not been studied in depth. This paper presents a case report of a 26-year-old male diagnosed with giant ameloblastoma of the mandible, accompanied by rare hypercalcemia. Additionally, a review of the relevant literature is conducted. This patient initially underwent marsupialization, yet this treatment was not effective, which indicated that the selection of the appropriate operation is of prime importance for improving the prognosis of patients with ameloblastoma. The tumor not only failed to shrink but gradually increased in size, accompanied by multiple complications including hypercalcemia, renal dysfunction, anemia, and cachexia. Due to the contradiction between the necessity of tumor resection and the patient's poor systemic condition, we implemented a multi-disciplinary team (MDT) meeting to better evaluate this patient's condition and design an individualized treatment strategy. The patient subsequently received a variety of interventions to improve the general conditions until he could tolerate surgery, and finally underwent the successful resection of giant ameloblastoma and reconstruction with vascularized fibular flap. No tumor recurrence or distance metastasis was observed during 5 years of follow-up. Additionally, the absence of hypercalcemia recurrence was also noted.

A novel postoperative nomogram and risk classification system for individualized estimation of survival among patients with parotid gland carcinoma after surgery.

BACKGROUND: Parotid gland carcinoma (PGC) is a rare but aggressive head and neck cancer, and the prognostic model associated with survival after surgical resection has not yet been established. This study aimed to construct a novel postoperative nomogram and risk classification system for the individualized prediction of overall survival (OS) among patients with resected PGC. METHODS: Patients with PGC who underwent surgery between 2004 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database were randomized into training and validation cohorts (7:3). A nomogram developed using independent prognostic factors based on the results of the multivariate Cox regression analysis. Harrell's concordance index (C-index), time-dependent area under the curve (AUC), and calibration plots were used to validate the performance of the nomogram. Moreover, decision curve analysis (DCA) was performed to compare the clinical use of the nomogram with that of traditional TNM staging. RESULTS: In this study, 5077 patients who underwent surgery for PGC were included. Age, sex, marital status, tumor grade, histology, TNM stage, surgery type, radiotherapy, and chemotherapy were independent prognostic factors. Based on these independent factors, a postoperative nomogram was developed. The C-index of the proposed nomogram was 0.807 (95% confidence interval 0.797-0.817). Meanwhile, the time-dependent AUC (> 0.8) indicated that the nomogram had a satisfactory discriminative ability. The calibration curves showed good concordance between the predicted and actual probabilities of OS, and DCA curves indicated that the nomogram had a better clinical application value than the traditional TNM staging. Moreover, a risk classification system was built that could perfectly classify patients with PGC into three risk groups. CONCLUSIONS: This study constructed a novel postoperative nomogram and corresponding risk classification system to predict the OS of patients with PGC after surgery. These tools can be used to stratify patients with high or low risk of mortality and provide high-risk patients with more directed therapies and closer follow-up.

Prediction of target genes in community-acquired pneumonia based on the bioinformatics method.

Background: To screen the related genes of community-acquired pneumonia (CAP) by bioinformatics technology, and to analyze the clinical value of key genes. Methods: Gene chip data sets containing CAP patients and normal controls were screened from the Gene Expression Omnibus (GEO) database. The downregulated differentially expressed genes (DEGs) were screened using a gene expression analysis tool (GEO2R). Simultaneously, gene set enrichment analysis (GSEA) was used to explore the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and core genes related to CAP. The candidate genes were then intersected with the genes reported in Online Mendelian Inheritance in Man (OMIM), and the clinical value of these candidate genes was examined based on a literature search. Finally, the clinical data of the CAP patients were retrospectively analyzed. Detect the type of pathogenic bacteria in bronchial-alveolar lavage fluid (BALF) using metagenomics next-generation sequencing (mNGS) high throughput sequencing technology, and detect the expression of key genes through liquid based cell immunohistochemistry to analyze the correlation between pathogenic bacteria and key genes. Results: Through the intersection of Venn diagrams, 175 co-expressed downregulated DEGs related to CAP were identified. A total of 4 candidate genes, including ICOS, IL7R, ITK, and ZAP70, were obtained by constructing the protein mutual aid network and conducting a module analysis of the common differentially expressed genes. The core genes in the GSEA enrichment pathways were intersected with the CAP-related genes reported in the relevant literature retrieved from the OMIM database. In the Venn diagram, two genes that coexist with OMIM include IL7R and PIK3R1. After considering our findings and the relevant literature, we determined that the key gene related to the occurrence and development of CAP was IL7R. The mNGS detected 13 kinds of bacteria, 4 kinds of fungi, and 2 kinds of viruses. Based on immunohistochemical results, it was found that there were relatively more bacteria detected in the IL7R high expression group. Conclusions: The identification of the key gene IL7R and the related signaling pathways extend understanding of the pathogenesis of CAP and provide a theoretical basis for clinical targeted therapy research.

CSNK1D-mediated phosphorylation of HNRNPA2B1 induces miR-25-3p/miR-93-5p maturation to promote prostate cancer cell proliferation and migration through m6A-dependent manner.

It has been reported that heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is highly expressed in prostate cancer (PCa) and associated with poor prognosis of patients with PCa. Nevertheless, the specific mechanism underlying HNRNPA2B1 functions in PCa remains not clear. In our study, we proved that HNRNPA2B1 promoted the progression of PCa through in vitro and in vivo experiments. Further, we found that HNRNPA2B1 induced the maturation of miR-25-3p/miR-93-5p by recognizing primary miR-25/93 (pri-miR-25/93) through N6-methyladenosine (m6A)-dependent manner. In addition, both miR-93-5p and miR-25-3p were proven as tumor promoters in PCa. Interestingly, by mass spectrometry analysis and mechanical experiments, we found that casein kinase 1 delta (CSNK1D) could mediate the phosphorylation of HNRNPA2B1 to enhance its stability. Moreover, we further proved that miR-93-5p targeted BMP and activin membrane-bound inhibitor (BAMBI) mRNA to reduce its expression, thereby activating transforming growth factor ß (TGF-ß) pathway. At the same time, miR-25-3p targeted forkhead box O3 (FOXO3) to inactivate FOXO pathway. These results collectively indicated that CSNK1D stabilized HNRNPA2B1 facilitates the processing of miR-25-3p/miR-93-5p to regulate TGF-ß and FOXO pathways, resulting in PCa progression. Our findings supported that HNRNPA2B1 might be a promising target for PCa treatment.

A Paper-Based Fluorescent Sensor for Rapid Early Screening of Oral Squamous Cell Carcinoma.

Various types of sensors play an irreplaceable role in the detection of biomarkers, but their high cost and complicated operation make it difficult to benefit ordinary people. Herein, we develop a low-cost, double-layered, paper-based fluorescent sensor (CP/HQ) structurally consisting of the upper reaction layer loaded with two oxidases (lactate oxidase and choline oxidase) and the bottom fluorescent layer that physically associates with the porphine-grafted composite fluorescent polymer colloids (PF-PDMTP/HQ). Based on the dramatic and rapid fluorescence decrease of porphine induced by the oxidation between saliva and oxidases and subsequent fluorescence resonance energy transfer from oxidized hydroquinone, the resultant fluorescent paper sensor enables us to achieve visual detection of OSCC, which was further recognized by smartphone scanning as the grayscale variation. It was found that the linear sensing range of grayscale value are 10-200 µM for lactic acid and 10-100 µM for choline, with LODs of 5.7 and 8.9 µM, respectively. More importantly, the sensor can achieve a powerful detection capability comparable to that of high-performance liquid chromatography (HPLC) in clinical settings with simple operation, demonstrating its great application potential. Our proposed sensor not only improves the accuracy of OSCC diagnosis but also provides a valuable attempt for the device modification of polymer-sensing systems and the development of non-invasive and easy-to-operate disease screening methods.

A novel nomogram and risk classification system for predicting overall survival in head and neck squamous cell cancer with distant metastasis at initial diagnosis.

INTRODUCTION: Head and neck squamous cell carcinoma (HNSCC) is one of the most invasive cancer types globally, and distant metastasis (DM) is associated with a poor prognosis. The objective of this study was designed to construct a novel nomogram and risk classification system to predict overall survival (OS) in HNSCC patients presenting with DM at initial diagnosis. METHODS: HNSCC patients with initially diagnosed DM between 2010 and 2015 were collected from the Surveillance, Epidemiology, and End Results (SEER) database. Firstly, all patients were randomly assigned to a training cohort and validation cohort (8:2), respectively. The Cox proportional hazards regression model was used to analyze the prognostic factors associated with OS. Then, the nomogram based on the prognostic factors and the predictive ability of the nomogram were assessed by the calibration curves, receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Finally, a risk classification system was established according to the nomogram scores. RESULTS: A total of 1240 patients initially diagnosed with HNSCC with DM were included, and the 6-, 12- and 18-month OS of HNSCC with DM were 62.7%, 40.8% and 30%, respectively. The independent prognostic factors for HNSCC patients with DM included age, marital status, primary site, T stage, N stage, bone metastasis, brain metastasis, liver metastasis, lung metastasis, surgery, radiotherapy and chemotherapy. Based on the independent prognostic factors, a nomogram was constructed to predict OS in HNSCC patients with DM. The C-index values of the nomogram were 0.713 in the training cohort and 0.674 in the validation cohort, respectively. The calibration curves and DCA also indicated the good predictability of the nomogram. Finally, a risk classification system was built and it revealed a statistically significant difference among the three groups of patients according to the nomogram scores. CONCLUSIONS: Factors associated with the overall survival of HNSCC patients with DM were found. According to the identified factors, we generated a nomogram and risk classification system to predict the OS of patients with initially diagnosed HNSCC with DM. The prognostic nomogram and risk classification system can help to assess survival time and provide guidance when making treatment decisions for HNSCC patients with DM.

The RNA demethylase ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the stability of the LncRNA PVT1.

BACKGROUND: N6-methyladenosine (m6A) is the most common posttranscriptional modification of RNA and plays critical roles in human cancer progression. However, the biological function of m6A methylation requires further studied in cancer, especially in tumor angiogenesis. METHODS: A public database was used to analyze the expression and overall survival of ALKBH5 and PVT1 in lung cancer patients. CCK-8 and colony formation assays were performed to detect cell proliferation, a transwell assay was used to assess cell migration, and a tube formation assay was performed to assess angiogenic potential in vitro. A zebrafish lung cancer xenograft model was used to verify the function of ALKBH5 and PVT1 in vivo. Western blot assays were used to measure the relative protein expression in lung cancer cells. SRAMP predictor analysis and RNA stability experiments were used to examine the potential m6A modification. RESULTS: Bioinformatics analysis showed that the expression levels of m6A-related genes were changed significantly in lung cancer tissues compared with normal lung tissues. We then identified that ALKBH5 was upregulated in lung cancer tissues and associated with poor prognosis of lung cancer patients by analyzing a public database. Knockdown of ALKBH5 inhibited the proliferation and migration of cultured lung cancer cell lines. Zebrafish lung cancer xenografts showed that ALKBH5 silencing also suppressed the growth and metastasis of lung cancer cells. Moreover, knockdown of ALKBH5 inhibited the angiogenesis of lung cancer in vitro and in vivo. Mechanistic studies showed that knockdown of ALKBH5 decreased the expression and stability of PVT1 in lung cancer cells. We next observed that PVT1 promoted the progression of lung cancer cells in vitro and in vivo and regulated the expression of VEGFA and angiogenesis in lung cancer. Finally, rescue experiments revealed that ALKBH5 regulated the proliferation, migration and angiogenesis of lung cancer cells, partially through PVT1. CONCLUSION: Our results demonstrate that ALKBH5 promotes the progression and angiogenesis of lung cancer by regulating the expression and stability of PVT1, which provides a potential prognostic and therapeutic target for lung cancer patients.

LINC01635, a long non-coding RNA with a cancer/testis expression pattern, promotes lung cancer progression by sponging miR-455-5p.

Long non-coding RNAs (lncRNAs) have been reported to play vital roles in human lung cancer. In recent years, cancer/testis (CT) lncRNAs have been characterized as a novel class of lncRNA. However, this class of lncRNA remains to be thoroughly investigated. The present study identified long intergenic non-protein coding RNA 1635 (LINC01635), which was highly expressed in testis and in a broad range of human cancer types. Next, it was confirmed that LINC01635 was upregulated significantly in samples from patients with lung cancer and in non-small cell lung carcinoma (NSCLC) cell lines. Silencing LINC01635 suppressed the proliferation and metastasis of NSCLC cells in vitro and in vivo. Furthermore, it was found that LINC01635 could bind to microRNA (miRNA or miR)-455-5p and regulate the expression of a series of miR-455-5p-targeting tumor-related genes. Knockdown of miR-455-5p partially rescued the progression of lung cancer cells that was suppressed by LINC01635 silencing. Together, the current results demonstrated that LINC01635 may play important roles in NSCLC progression by targeting miR-455-5p, and that it could be a biomarker and therapeutic target for lung cancer.

Significance of hereditary gene alterations for the pathogenesis of adult bone marrow failure versus myeloid neoplasia.

Broader genetic screening has led to the growing recognition of the role of germline variants associated with adult bone marrow failure (BMF) and myeloid neoplasia (MN) not exclusively in children and young adults. In this study, we applied a germline variant panel to 3008 adult BMF and MN cases to assess the importance of germline genetics and its impact on disease phenotype and prognosis. In our cohort, up to 9.7% of BMF and 5.3% of MN cases carried germline variants. Our cohort also included heterozygous carriers of recessive traits, suggesting they contribute to the risk of BMF and MN. By gene category, variants of Fanconi anemia gene family represented the highest-frequency category for both BMF and MN cases, found in 4.9% and 1.7% cases, respectively. In addition, about 1.4% of BMF and 0.19% of MN cases harbored multiple germline variants affecting often functionally related genes as compound heterozygous. The burden of germline variants in BMF and MN was clearly associated with acquisition of monosomy 7. While BMF cases carrying germline variants showed similar overall survival as compared to the wild-type (WT) cases, MN cases with germline variants experienced a significantly shorter overall survival as compared to WT cases.

Study on the Mechanism of Action of Paclitaxel-Loaded Polylactic-co-glycolic Acid Nanoparticles in Non-Small-Cell Lung Carcinoma Cells.

Objective: To study effective carriers that can enhance the antitumor effect of paclitaxel (PTX). Methods: PTX-loaded polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) (PTX-PLGA NPs), constructed using the emulsification solvent evaporation method, were characterized by scanning electron microscopy and dynamic light scattering. Non-small-cell lung carcinoma (NSCLC) cells were divided into the dimethyl sulfoxide (DMSO) group, PLGA NPs group, PTX group, and PTX-PLGA NPs group. Cell viability was detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), cell apoptosis was determined by flow cytometry, and cell migration and invasion were assessed using Transwell assay. Results: PTX-PLGA NPs were smooth in the surface and spherical in shape, with a particle size of 268 ± 1.3 nm. Both PTX and PTX-PLGA NPs could effectively inhibit the activity of A549 and H1650 cells. At 12 and 24 h, PTX-PLGA NPs presented weaker inhibition on the activity of NSCLC cells than PTX, but at 48 and 72 h, PTX-PLGA NPs presented stronger inhibition. Compared with PTX, PTX-PLGA NPs were more effective in enhancing apoptosis and inhibiting migration and invasion of NSCLC cells. Conclusion: With good sustained release and the ability to promote cellular uptake, PTX-PLGA NPs can strongly inhibit the malignant activities of NSCLC cells, which can be used as a promising drug carrier.

The roles of symbolic and numerical representations in asymmetric visual search.

This study aims to explore the impact of symbolic and numerical representations in asymmetric visual search. Heterogeneous and homogeneous mathematical units, letters, symbols and numbers were used in the first and second experiments, respectively. Target was searched among 6 or 12 stimuli. Analysis showed that the search efficiency was greatest in LaS (large among small), but the performance decreased significantly in SaS (small among small). Moreover, LaS was faster than SaL (small among large). However, SaL was faster than LaL (large among large) and LaL was faster than SaS. The findings of this study showed that the search efficiency was indirectly proportional to the number of stimuli. This implies that processing of visual stimuli of different sizes and appearance was asymmetric, all requiring varied attention. In summary, these findings strengthen the integration theory, similarity theory and guided search model.

ARHGAP24 ameliorates inflammatory response through inactivating Rac1/Akt/NF-κB pathway in acute pneumonia model of rat.

BACKGROUND: ARHGAP24 might play a protective effect in the development of acute pneumonia, but the underlying mechanism remained a mystery. We aimed to investigate the effect of ARHGAP24 and explore the protective mechanism based on the acute pneumonia model of rats. METHODS: Western blotting analysis was conducted to measure the expression of ARHGAP24 in the rat model of bacillus pyocyaneus-induced acute pneumonia after 12, 24, 36, and 48 h modeling. In the acute pneumonia model of rat, lung histopathological change, lung edema, and levels of inflammatory cytokines in the broncho alveolar lavage fluid (BALF) were respectively measured to comprehensively evaluate the beneficial effect of overexpression of ARHGAP24 mediated by adenovirus. The western blotting analysis was conducted to evaluate Rac1/Akt/NF-κB pathway-related protein expression change with ARHGAP24 overexpression. RESULTS: We found that ARHGAP24 expression tended to be lower in the acute pneumonia model of the rat after bacillus pyocyaneus treated 12, 24, 36, and 48 h. High expression of ARHGAP24 and a substantial ARHGAP24 positive area was found in the western blotting analysis and immunohistochemical staining in rats transfected with ARHGAP24. In the meantime, overexpression of ARHGAP24 suppressed the development of acute pneumonia through alleviating lung histopathological deterioration, lung edema, and levels of inflammatory cytokines in the BALF of the lung. What is more critical, ARHGAP24 overexpression inhibits the activation of Rac1, Akt, and NF-κB. CONCLUSIONS: Thus, we conclude that ARHGAP24 ameliorated the inflammatory response in the acute pneumonia model of the rat through inactivating the Rac1/Akt/NF-κB pathway.

Zebrafish xenograft model of human lung cancer for studying the function of LINC00152 in cell proliferation and invasion.

BACKGROUND: Numerous studies have shown that long noncoding RNAs play important roles in human cancer progression. Although zebrafish xenografts have recently become a novel in vivo model for human cancer research, whether such models can be used to study the function of long noncoding RNAs remains unknown. METHODS: In vitro studies validated the roles of LINC00152 in the proliferation and invasion of lung cancer cells. In vivo studies of zebrafish xenografts also confirmed these roles of LINC00152. In vivo confocal imaging was used to more accurately evaluate the function of LINC00152 in cell proliferation and migration. Pharmacological experiments were further performed to study the potential ability of LINC00152 downregulation combined with an EGFR inhibitor to treat tumors in cultured cells and the zebrafish xenograft model. RESULTS: Silencing of LINC00152 suppressed cell proliferation and invasion in SPCA1 and A549 lung cancer cell lines in vitro. In the zebrafish xenograft model, knockdown of LINC00152 reduced the proliferation and migration of lung cancer cells, as indicated by the two imaging methods at different magnifications. Moreover, the knockdown of LINC00152 enhanced the inhibition effect of afatinib for lung cancer progression in cultured cells and the zebrafish xenograft model. CONCLUSION: Our study reveals the oncogenic roles and potential for LINC00152 to be a target for tumor treatment in lung cancer using zebrafish xenograft models, and the findings suggest that this model could be used for functional and application studies of human long noncoding RNAs in tumor biology.

Circular RNA Circ-ZNF609 Promotes Lung Adenocarcinoma Proliferation by Modulating miR-1224-3p/ETV1 Signaling.

BACKGROUND: Circ-ZNF609 has been shown to modulate cancer progression in several kinds of cancer. However, the role of circ-ZNF609 played in lung adenocarcinoma (LAUD) remains unclear. In this study, we investigated the role of circ-ZNF609 in regulating LAUD cancer progression. MATERIALS AND METHODS: Quantitative reverse transcription polymerase chain reaction was conducted to evaluate circ-ZNF609 expression in 52 LAUD tissues and 52 matched adjacent normal tissues, LAUD cell lines and bronchial epithelial cell line (HBE). The direct interaction between miR-1224-3p and circ-ZNF609 or EVT1 was verified using luciferase reporter assay and RNA immunoprecipitation assay. Cell Counting Kit-8, colony formation assay, cell-cycle analysis were utilized to examine the effect of circ-ZNF609 or miR-1224-3p on cell proliferation. RESULTS: Circ-ZNF609 was significantly upregulated in LAUD tissues and cell lines, and its inhibition induced reduced cell proliferation of LAUD cells. Mechanistically, we demonstrated that circ-ZNF609 sponged miR-1224-3p to promote EVT1 expression. More importantly, miR-1224-3p overexpression strongly suppressed circZNF609-induced malignant phenotype of LAUD cells. CONCLUSION: Circ-ZNF609 enhances LAUD progression by increasing oncogenic EVT1 expression via sponging miR-1224-3p, revealing that circ-ZNF609/miR-1224-3p/ETV1 axis may be a promising therapeutic target for LAUD treatment.

A Novel Long Non-coding RNA, MSTRG.51053.2 Regulates Cisplatin Resistance by Sponging the miR-432-5p in Non-small Cell Lung Cancer Cells.

Objective: The aim of this study was to investigate the molecular mechanisms underlying cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) cells by constructing a competing endogenous RNA (ceRNA) network. Methods: The gene expression profiles of human lung adenocarcinoma DDP-resistant cell line (A549/DDP) and its progenitor (A549) were comparatively evaluated by whole-transcriptome sequencing. The differentially expressed genes (DEGs) were subjected to KEGG pathway analysis. The expression levels of mRNAs involved in several pathways associated with conferring DDP resistance to tumor cells were evaluated. The ceRNA network was constructed based on the mRNA expression levels and the sequencing data of miRNA and lncRNA. Several ceRNA regulatory relationships were validated. Results: We quantified the expression of 17 genes involved in the six pathways by quantitative real-time polymerase chain reaction (qRT-PCR). The differential protein expression levels of eight genes were quantified by western blotting. Western blot analysis revealed six differentially expressed proteins (MGST1, MGST3, ABCG2, FXYD2, ALDH3A1, and GST-ω1). Among the genes encoding these six proteins, ABCG2, ALDH3A1, MGST3, and FXYD2 exhibited interaction with 8 lncRNAs and 4 miRNAs in the ceRNA regulatory network. The expression levels of these lncRNAs and miRNAs were quantified in cells; among these, 6 lncRNAs and 4 miRNAs exhibited differential expression between A549/DDP and A549 groups, which were used to construct a ceRNA network. The ceRNA regulatory network of MSTRG51053.2-miR-432-5p-MGST3 was validated by luciferase reporter assay. Conclusion: The MSTRG51053.2 lncRNA may function as a ceRNA for miR-432-5p to regulate the DDP resistance in NSCLC. The MGST1, MGST3, GST-ω1, and ABCG2 mRNAs, miR-432-5p and miR-665 miRNAs, and MSTRG51053.2 and PPAN lncRNAs can serve as potential DDP drug targets to reverse DDP resistance in NSCLC.

Down-regulation of MBNL1-AS1 contributes to tumorigenesis of NSCLC via sponging miR-135a-5p.

Lung cancer remains a big threat to human health. Growing evidence has reported the crucial regulatory effect of lncRNAs on NSCLC progression. Nevertheless, the detailed function of lncRNA MBNL1-AS1 involved in NSCLC development is poorly known. In our research, we confirmed that MBNL1-AS1 was significantly reduced in NSCLC patient tissues and NSCLC cells. Meanwhile, we reported that overexpression of MBNL1-AS1 obviously repressed A549 and H1975 cell proliferation, blocked cell cycle and inhibited the migration and invasion. Moreover, A549 and H1975 cell apoptosis was increased by the overexpression of MBNL1-AS1. Then, we predicted that miR-135a-5p was a potential target of MBNL1-AS1 and its level was correlated with MBNL1-AS1 in NSCLC negatively. Our previous study indicated miR-135a-5p could induce lung cancer progression through regulating LOXL4. Here, we found that MBNL1-AS1 was able to regulate miR-135a-5p expression negatively. The direct binding association between MBNL1-AS1 and miR-135a-5p was proved using dual-luciferase reporter assay and RIP experiment. Subcutaneous xenotransplanted tumor model was set up and it was confirmed increased MBNL1-AS1 remarkably restrained tumorigenic ability of NSCLC through sponging miR-135a-5p in vivo. To sum up, our data revealed the significance of the MBNL1-AS1 and miR-135a-5p in NSCLC. In conclusion, MBNL1-AS1 could be a new therapeutic target to treat NSCLC.

Risk factors of coronary artery stenosis in patients with obstructive sleep apnoea: a prospective study.

OBJECTIVE: To investigate the prevalence of coronary artery disease and characteristics of coronary artery in patients with obstructive sleep apnoea. METHODS: The prospective study was conducted at the Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China, from January, 2012, to June, 2015, and comprised consecutive patients with diagnosed obstructive sleep apnoea. High-resolution 320-slice coronary computed tomography was performed in all the patients. Data was evaluated for the presence of coronary lumen narrowing. Demographic, clinical, laboratory, and echocardiographic characteristics were carefully recorded. Logistic regression was used for multivariate analysis of independent risk factors. SPSS 16 was used for data analysis. RESULTS: Of the 277 patients, 186(67.14%) were males. The overallmean age was 55.1±14.3 years. Coronary artery disease was found in 41(14.8%) patients. Prospective Cardiovascular Münster score, uric acid, triglyceride, C-reactive protein, apnoea hypopnoea index, Epworth sleepiness scale values were significantly higher in patients with the disease (p<0.05 each). Higher Prospective Cardiovascular Münster score, C-reactive protein, apnoea hyponoea index levels had a significant ability to reflect the occurrence of coronary artery disease (p<0.05 each). CONCLUSIONS: Coronary heart disease occurrence in obstructive sleep apnoea patients was found to be strongly related to Prospective Cardiovascular Münster score, apnoea hyponoea index and Creactive protein level.