Gastric cancer (GC) is one of the most frequent digestive system cancers and is the second cause of cancer mortality worldwide by 2018. 1 The cases in China account for more than 40% of the total number of GC worldwide due to a high incidence rate and a large population. 2 Moreover, the GC patients were more likely to be in the advanced stage when diagnosed because of non-early specific symptoms.Unfortunately, the late diagnosis can significantly affect the 5-year survival rate. In the past decade, due to the advancement of treatment and medicine, the GC prognosis has improved, but it is still not satisfied due to the relatively short disease-free survival duration. 3 Thus, it is challenging and necessary to explore the underlying mechanisms of GC and identify novel biomarkers or treatment targets.

Ovarian cancer is one of the most common lethal gynecological malignancies worldwide. Abnormal kinesin family member 4A (KIF4A) expression has been implicated in ovarian cancer progression; however, the potential mechanism underlying KIF4A in ovarian cancer is not completely understood. The present study aimed to clarify the molecular basis of KIF4A in ovarian cancer. KIF4A and budding uninhibited by benzimidazoles 1 (BUB1) expression levels were detected via reverse transcription-quantitative PCR and western blotting. Cell Counting Kit-8, colony formation, wound healing, TUNEL and flow cytometry assays were performed to assess cell proliferation, migration, apoptosis and cell cycle distribution, respectively. Ki67 expression levels were detected by conducting immunofluorescence assays. The expression levels of migration-and apoptosis-related proteins were measured via western blotting. A co-immunoprecipitation assay was conducted to determine the association between KIF4A and BUB1. The results demonstrated that KIF4A was expressed at significantly higher levels in ovarian cancer cell lines compared with IOSE-80 cells. Compared with the short hairpin RNA-negative control group, KIF4A knockdown significantly inhibited cell viability, colony formation and migration, and markedly induced cell apoptosis. The results indicated that KIF4A could bind to BUB1 and regulate BUB1 expression. BUB1 overexpression weakened KIF4A knockdown-mediated effects on cell viability, colony formation, migration and apoptosis. Overall, the present study demonstrated that KIF4A knockdown suppressed ovarian cancer progression by regulating BUB1, and suggested the potential value of KIF4A and BUB1 as therapeutic targets for ovarian cancer.

Congenital factor V deficiency is a rare bleeding disorder characterized by low coagulant activity, associated with variable phenotypic expression. Among rare inherited coagulopathies, the molecular basis of factor V deficiency is rarely described because of its relatively low prevalence in the general population. Recently, we detected two genetic variations in factor V of a Chinese patient with hereditary factor V deficiency. One was a heterozygous nonsense mutation, C67868T in exon 22, which resulted in Gln2031stop substitution in the C1 domain of factor V. The other was a previously described polymorphism, G1618A in exon10, leading to Arg485Lys substitution. We deduced that the nonsense mutation is responsible for the factor V deficiency, whereas the Arg485Lys polymorphism is expected to compensate for the low plasma factor V levels. Of note, the nonsense mutation has been confirmed to be a novel mutation.

Background: Gastric cancer (GC) is one of the common digestive malignancies worldwide and causes a severe public health issue. So far, the underlying mechanisms of GC are largely unclear. Thus, our aim is to identify the long non-coding RNA (lncRNA) associated competing endogenous RNA (ceRNA) specialized for occurrence and progression in GC.Methods: The comprehensive online dataset, TCGA, was downloaded and used for identification of differentially expressed (DE) lncRNA, miRNA and mRNA screen with the value of logFC = 1 and FDR < 0.05, respectively. The interactions between lncRNA and miRNA as well mRNA and miRNA were predicted via multiple online databases, such as miRcode and Targetscan. Then the ceRNA network was constructed accompanied with gene set enrichment analysis and survival analysis. In addition, RT-qPCR and in vitro assay was carried out to validate the effect of the hub lncRNAs.Results: We identified 1485 lncRNAs, 312 miRNAs and 4260 mRNAs were differentially expressed between GC and normal tissues, respectively. Then, we generated a ceRNA network with 909 edges and 253 nodes including 76 lncRNA, 18 miRNA and 159 mRNA. This ceRNA network was involved in MET activates PTK2 signalling, MET promotes cell motility and non-integrin membrane-ECM interactions. Next, by univariate and multivariate analysis, there were 9 hub lncRNAs emerged and were associated subnetwork involved in actin filament binding and MAPK signaling pathway. The in vitro assay indicated lncRNA INHBA-AS1 and CCDC144NL-AS1 may positively related to the GC aggressive features, including proliferation, invasion and migration.Conclusion: In summary, we constructed a ceRNA network involved in the GC development. Moreover, we also identified 9 hub lncRNA-associated network related to prognosis of GC and validated two out of them as promising oncogenes. This may provide potential biomarkers or therapeutic target for GC in future.