BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) promotes lung adenocarcinoma by interacting with Zinc Finger Protein ZNF143 and regulating glycolysis.

Lung adenocarcinoma (LUAD) is one of the most common causes of cancer death in men. BUB1B (BUB1 mitotic checkpoint serine/threonine kinase B) has been reported to contribute to the initiation and development of several cancers. Here, we aimed to explore the potential role of BUB1B in LUAD. We found BUB1B was upregulated in LUAD, suggesting its potential role as a biomarker for LUAD diagnosis. Significantly, LUAD patients with high BUB1B expression had a shorter survival time than those with low BUB1B expression. Knocking-out BUB1B resulted in suppression of cell proliferation, migration, and invasion in vitro, and inhibition of tumor growth in the xenograft experiment. Further analysis revealed that BUB1B regulates glycolysis in LUAD and interacting with ZNF143 in LUAD cells. The interaction was demonstrated by silencing ZNF143, which led to a decrease in proliferation, migration, and invasion in LUAD cells, whereas overexpressing BUB1B had the opposite effects. Our study suggested that the ZNF143/BUB1B axis plays a pivotal role in LUAD progression, which might be a potential target for LUAD management.

Neutrophils correlate with hypoxia microenvironment and promote progression of non-small-cell lung cancer.

Hypoxia, a strong and selective pressure, has been involved in invasion, metastasis, and angiogenesis of tumor cells. Our study performed the transcriptome profiles of 666 non-small-cell lung cancer (NSCLC) patients. Various bioinformatic approaches were combined to evaluate the immune cell infiltration in the high hypoxia risk patients. In addition, in vitro experiments were performed to assess the effects of tumor-associated neutrophils (TANs) on NSCLC cells proliferation, migration and invasion and to reveal the underlying mechanisms. We divided NSCLC into two groups (Cluster1/2) based on the expression profiles of hypoxia-associated genes. Compared with the Cluster1 subgroup, the Cluster2 had a worse prognosis. Significant enrichment analysis revealed that PI3K/AKT/mTOR signaling pathway and TANs were highly related to hypoxia microenvironment. Eleven hypoxia-related genes (FBP1, NDST2, ADM, LDHA, DDIT4, EXT1, BCAN, IGFBP1, PDGFB, AKAP12, and CDKN3) were scored by LASSO COX regression to yield risk scores, and we revealed a significant difference in overall survival (OS) between the low- and high-risk groups. Mechanistically, CXCL6 in hypoxic cancer cells promoted the migration of TANs in vitro, and in turn promote NSCLC cells proliferation, migration and invasion. In summary, this study revealed a 11-hypoxia gene signature that predicted OS of NSCLC patients, and improved our understanding of the role of TANs in hypoxia microenvironment.

MicroRNA-20a-5p suppresses tumor angiogenesis of non-small cell lung cancer through RRM2-mediated PI3K/Akt signaling pathway.

The current therapeutic strategies for non-small cell lung cancer (NSCLC) are limited and unsatisfactory. MicroRNAs (miRNAs) participate in tumor angiogenesis in NSCLC. The aim of this study was to investigate the role of miR-20a-5p (miR-20a) in human NSCLC metastasis. In the current study, bioinformatics analysis and RT-PCR were performed to examine the expression level of miR-20a in tissues of NSCLC patients and NSCLC cell lines, respectively. Western blot was performed to test the protein levels. Cell proliferation, migration and angiogenesis capacity were tested by 5-ethynyl-29-deoxyuridine (EdU) assay, transwell assay and tube formation assay, respectively. Dual-luciferase reporter assay (DLR) was used to confirm the interaction between miR-20a and paired ribonucleotide reductase regulatory subunit M2 (RRM2). We found that the expression of RRM2 was upregulated, while the expression of miR-20a was downregulated in cancer tissues compared with adjacent tissues in NSCLC patients. We also detected the expression level of RRM2 and miR-20a in NSCLC cell lines, showing A549 cell line exhibited the lowest expression level of miR-20a and highest expression level of RRM2. Overexpressed miR-20a not only dramatically suppressed NSCLC cells proliferation, endothelial cells migration and tube formation in vitro, but also inhibited tumor growth and angiogenesis in vivo. It was demonstrated that miR-20a suppressed NSCLC growth by inhibiting RRM2-mediated PI3K/Akt signaling pathway. These findings indicate that the novel identified miR-20a could function as a tumor suppressor in NSCLC through modulating the RRM2-mediated PI3K/Akt axis, and it could be a valid molecular target for NSCLC treatment.

[Epidemiological survey on bronchial asthma in Henan province].

OBJECTIVE: To survey asthma prevalence, correlation factors for prevention, treatment, and for policy decision of asthma control. METHODS: Done with TB epidemiological survey synchronously, sampling by stratified-cluster-random method. 43 points were selected and distributed in all 18 prefectures in Henan province. Sampling population was 75 134, and 65 033 (97.0%) were investigated actually. RESULTS: In this survey, 682 asthma patients were found. The total prevalence rate was 1.05%, the rate for children was 1.71%, and that for adult was 0.82%; the rates for male and female were 1.16%, 0.94% respectively. The ratio of male to female was 1.23:1. When asthmatic chronic bronchitis cases were regarded as asthma cases and included in total asthma cases, the overall prevalence rate of asthma would increase up to 1.73%, raised by 65%. The higher prevalence were in 0 approximately 3 years old age group (4.48%) and >/= 65 years old age group (1.43%), the lowest prevalence was in 15 approximately 24 years old age group (0.36%). For 90% of asthmatic children, the initiative age of asthma was before 7 years old, and for 1/3 adult patient, it was in childhood. The prevalence of asthma in rural area was higher than that of urban area. Cold air, common cold, stimulation of smoking and cooking, and room dust were the 4 main inducing factors. Seasonal attack of asthma accounted for 67.2%, and that in winter and spring was 65.4%. 60.6% of asthma cases showed history of allergic diseases including allergic rhinitis, dermatitis, and drug allergy; 34.3% asthma family history. CONCLUSIONS: The rate of prevalence and inducing factors of asthma in Henan province were gained in this survey. The results may basically reflect the present status and be provided for asthma control as reference. According to the prevalence, asthma cases would be up to 0.98 approximately 1.6 million in whole Henan province and more attention should be paid to this situation.