Epithelial-mesenchymal transition (EMT) is an important biological process that is characteristic of malignant tumor cells with metastatic potential. We investigated the role of miR-551b in EMT and metastasis in gastric cancer (GC). We found that low miR-551b levels were associated with EMT, metastasis and a poor prognosis in GC patients. Further, two GC cell lines, MNK45 and SGC7901, exhibited lower miR-551b levels than the GES normal stomach cell line. Exposing MNK45 and SGC7901 cells to TGF-β1 resulted in cell morphology changes characteristic of EMT, which was confirmed by Western blot analysis demonstrating low E-Cadherin and high N-Cadherin and Vimentin levels. Treatment with miR-551b mimics inhibited these EMT changes as well as Transwell migration and invasiveness. We identified ERBB4 as a potential target of miR-551b based on patient data from the TCGA. ERBB4 was upregulated in GC specimens, and its high expression correlated with a poor prognosis of GC patients. Dual luciferase assays revealed that miR-551b directly inhibited ERBB4 by binding to its 3′UTR. Moreover, treatment with miR-551b mimics or the ERBB4 inhibitor AST-1306 inhibited EMT in the GC cell lines. Finally, nude mice xenografted with GC cancer cell lines expressing miR-551b mimics exhibited smaller tumors and longer survival than mice engrafted with control GC cancer cells. These data indicate that miR-551b inhibits EMT and metastasis in GC by inhibiting ERBB4. miR-551b and ERBB4 are thus potential therapeutic targets for the treatment of GC.
Charcot-Marie-Tooth (CMT) disease is the most common hereditary peripheral neuropathy. More than 50 causative genes have been identified. The lack of genotype-phenotype correlations in many CMT patients make it difficult to decide which genes are affected. Recently, targeted next-generation sequencing (NGS) has been introduced as an alternative approach for diagnosis of genetic disorders. Here, we applied targeted NGS in combination with PMP22 duplication/deletion analysis to screen causative genes in 22 Chinese CMT families. The novel variants detected by targeted NGS were then further studied in cultured cells. Of the 22 unrelated patients, 8 had PMP22 duplication. The targeted NGS revealed 10 possible pathogenic variants in 11 patients, including 7 previously reported variants and 3 novel heterozygous variants (GJB1: p.Y157H; MFN2: p.G127S; YARS: p.V293M). Further classification of the novel variants according to American College of Medical Genetics and Genomics (ACMG) standards and guidelines and functional analysis in cultured cells indicated that p.Y157H in GJB1 was pathogenic, p.G127S in MFN2 was likely pathogenic, while p.V293M in YARS was likely benign. Our results suggest the potential for targeted NGS to make a more rapid and precise diagnosis in CMT patients. Moreover, the functional analysis is required when the novel variants are indistinct.
The study aimed to investigate the expression and significance of the plasma let-7 family in anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Blood samples from 5 anti-NMDAR encephalitis patients and 5 negative controls were collected for microarray analysis. Blood samples from10 anti-NMDAR encephalitis patients, 10 anti-NMDAR encephalitis patients whose physical conditions have improved after 3 months of immunotherapy, 20 virus (meningitis) encephalitis patients, 20 tuberculosis (meningitis) encephalitis patients, 10 purulent (meningitis) encephalitis patients, 20 cerebral cysticercosis patients, 20 ischemic stroke patients, 20 intracerebral hemorrhage patients, 15 neuromyelitis optica patients, 15 multiple sclerosis patients, 15 moyamoya disease patients, and 20 negative controls were collected for real-time quantitative PCR (qRT-PCR) analysis. The expression levels of let-7a, let-7b, let-7d, and let-7f were significantly down-regulated in anti-NMDAR encephalitis compared with the negative controls (NC). The expression levels of let-7a, let-7d, and let-7f were significantly down-regulated in other nervous system diseases compared with the NC group while the expression level of let-7b was statistically insignificant in other nervous system diseases compared with the NC group. In addition, there was no significant dysregulation of let-7b in the anti-NMDAR encephalitis treatment group compared with the NC. Let-7b may be a potential diagnostic marker and an indicator that reflected the molecular mechanism of anti-NMDAR encephalitis.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.