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BackgroundDysregulated miR-7 and aberrant NF-κB activation were reported in various human cancers. However, the expression profile, clinical relevance and dysregulated mechanism of miR-7 and NF-κB RelA/p65 in human gastric cancers (GC) metastasis remain largely unknown. This study is to investigate the expression profile, clinical relevance and dysregulated mechanism of miR-7 and NF-κB RelA/p65 in GC and to explore the potential therapeutic effect of miR-7 to GC distant metastasis.MethodsTCGA STAD and NCBI GEO database were used to investigate the expression profile of miR-7 and NF-κB RelA/p65 and clinical relevance. Lentivirus-mediated gene delivery was applied to explore the therapeutic effect of miR-7 in GC. Real-time PCR, FACS, IHC, IF, reporter gene assay, IP, pre-miRNA-7 processing and binding assays were performed.ResultsLow miR-7 correlated with high RelA/p65 in GC with a clinical relevance that low miR-7 and high RelA/p65 as prognostic indicators of poor survival outcome of GC patients. Moreover, an impaired pre-miR-7 processing caused by dysregulated Dicer1 expression is associated with downregulated miR-7 in GC cells. Functionally, delivery of miR-7 displays therapeutic effects to GC lung and liver metastasis by alleviating hemangiogenesis, lymphangiogenesis as well as inflammation cells infiltration. Mechanistically, miR-7 suppresses NF-κB transcriptional activity and its downstream metastasis-related molecules Vimentin, ICAM-1, VCAM-1, MMP-2, MMP-9 and VEGF by reducing p65 and p-p65-ser536 expression. Pharmacologic prevention of NF-κB activator LPS obviously restored miR-7-suppressed NF-κB transcriptional activation and significantly reverted miR-7-inhibited cell migration and invasion.ConclusionsOur data suggest loss of miR-7 in GC promotes p65-mediated aberrant NF-κB activation, facilitating GC metastasis and ultimately resulting in the worse clinical outcome. Thus, miR-7 may act as novel prognostic biomarker and potential therapeutic target for aberrant NF-κB-driven GC distant metastasis.Electronic supplementary materialThe online version of this article (10.1186/s13046-019-1074-6) contains supplementary material, which is available to authorized users.

Purpose: The purpose of this study was to document the ability of single-nucleotide polymorphism microarray to identify copy-neutral regions of homozygosity, demonstrate clinical utility of regions of homozygosity, and discuss ethical/legal implications when regions of homozygosity are associated with a parental blood relationship. methods: Study data were compiled from consecutive samples sent to our clinical laboratory over a 3-year period. A cytogenetics database identified patients with at least two regions of homozygosity >10 Mb on two separate chromosomes. A chart review was conducted on patients who met the criteria.

SummaryBackground Although some features of dermatomyositis (DM) and polymyositis (PM) have been reported as possible prognostic indicators for cancer development, previous studies were small in size and were unable to establish a definitive relationship between neoplasms and DM and PM. Objectives To evaluate risk factors for developing malignancies in patients with DM and PM. Methods Meta-analysis of the studies reported in the literature was performed to unveil risk factors for developing cancer among patients with DM and PM. The included studies were either cohort or retrospective case-control studies with information on cancer status. Risk for malignancy was determined as the odds ratio (OR) or weighted mean difference (WMD) with a 95% confidence interval (CI), determined by fixed and random effects models. Stata 10.0 software was used to identify possible publication bias. Results Twenty studies with 380 patients and 1575 controls were included in the analysis. The factors that may increase the risk of cancer in patients with DM and PM were older age (WMD 11Á41, 95% CI 9Á84-12Á98), male sex (OR 1Á92, 95% CI 1Á49-2Á48), cutaneous necrosis (OR 5Á52, 95% CI 3Á49-8Á74) and dysphagia (OR 2Á41, 95% CI 1Á50-3Á86), whereas those that may provide protection against cancer included arthritis (OR 0Á38, 95% CI 0Á24-0Á61) and interstitial lung disease (OR 0Á32, 95% CI 0Á20-0Á51). Conclusions Our data suggest that age, sex, cutaneous necrosis, dysphagia, arthritis and lung complications may influence susceptibility to cancer in patients with DM and PM.