Circ_0111277 suppresses trophoblast cell proliferation, angiogenesis, migration, invasion and EMT via regulating miR-188-3p/GRHL2 axis.

PROBLEM: Preeclampsia (PE) is the main factor threatening the life of primipara. Defective migration and invasion of trophoblast cells was one of the causes of PE. Circ_0111277 had been reported to be related to the development of PE, but the mechanism of its effect on trophoblast cells needed further study. METHOD OF STUDY: The expression of circ_0111277, microRNA-188-3p (miR-188-3p) and grainyhead-like 2 (GRHL2) mRNA were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) assay, 5-Ethynyl-20-deoxyuridine (EdU) and colony formation assay were used to examine cell proliferation ability. Tube formation and transwell assay were performed to assess the angiogenesis and metastasis ability of cells. Western blot was applied to measure the levels of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin and Vimentin) and GRHL2 protein. The relationship between miR-188-3p and circ_0111277 or GRHL2 was verified by the dual luciferase reporter experiment. RESULTS: Circ_0111277 and GRHL2 were elevated, and miR-188-3p was declined in PE patients. Overexpression of circ_0111277 could inhibit the proliferation, angiogenesis, migration, invasion and EMT of trophoblast cells (HTR-8/Svneo). Circ_0111277 was the molecular sponge of miR-188-3p. MiR-188-3p up-regulation could reduce the inhibition of HTR-8/Svneo cell growth caused by overexpression of circ_0111277. GRHL2 was a target gene of miR-188-3p, and GRHL2 silencing relieved the adverse effects of miR-188-3p inhibitors on HTR-8/Svneo. In general, circ_0111277 up-regulated GRHL2 expression through sponge miR-188-3p. CONCLUSION: Highly expressed circ_0111277 up-regulated the expression of GRHL2 through sponge miR-188-3p, thereby inhibiting trophoblast cells function, which suggested a new molecular mechanism for the pathogenesis of PE.

Early-onset familial Alzheimer's disease in a family with mutation of presenilin 2 gene. / ä¸€ä¸ªæ—©è€ç´ 2åŸºå› çªå˜å¯¼è‡´çš„æ—©å‘å®¶æ—æ€§é˜¿å°”èŒ¨æµ·é»˜ç— å®¶ç³».

Alzheimer's disease (AD) is the most common senile neurodegenerative disease characterized by progressive cognitive dysfunction, psychological and behavioral abnormalities, and impaired ability of activities of daily living. A family with a total of 3 patients were admitted to the Department of Neurology of Xiangya Hospital, Central South University in 2018. The proband showed memory decline as the presenting symptoms, and subsequently showed psychological and behavioral abnormalities, personality changes, seizures, and motor retardation. Definite diagnosis of early-onset familial AD (EOFAD) with missense mutation of presenilin 2 (PSEN2) (c.715A>G p.M239V) was established by whole exome sequencing (WES) technology. We reported the mutation in Chinese Han population for the first time, which expanded the mutation spectrum ofPSEN2 gene and aid to enrich the characterization of clinical phenotype in EOFAD associated to PSEN2 mutations. Patients with early onset age and complex clinical manifestations of AD can be diagnosed with the help of genetic testing to avoid misdiagnosis.

Lack of association between LGMN and Alzheimer's disease in the Southern Han Chinese population.

Recently, functional studies have demonstrated that legumain (LGMN) cleaves both amyloid ß-protein precursor and tau, promoting senile plaques and formation of neurofibrillary tangles, which may play a crucial role in the pathogenesis of Alzheimer's disease (AD). However, the genetic role of LGMN in AD has not been clearly elucidated. Here, we used Sanger sequencing to investigate the single independent (single-variant association test) and cumulative (gene-based association test) effects of variants in the LGMN gene as potential susceptibility factors for AD, in a cohort comprising 676 AD cases and 365 elderly controls from the Han population of South China. In single-variant association analysis, none of the common variants in LGMN were statistically significant. In gene-based analysis, the LGMN gene also showed no association with AD. The results of our replication study in the Alzheimer's Disease Neuroimaging Initiative cohort also showed no association between LGMN and AD. These findings suggest that the LGMN gene may not be a critical factor for AD development.

Identification of expanded repeats in NOTCH2NLC in neurodegenerative dementias.

Recently, the (GGC)n repeat expansion in the NOTCH2NLC gene has been identified to be associated with neuronal intranuclear inclusion disease (NIID). Given the clinical overlap of dementia-dominant NIID with neurodegenerative dementia, we therefore hypothesized that the NOTCH2NLC repeat expansion might also contribute to these diseases. In the present study, repeat primed polymerase chain reaction (RP-PCR) and GC-rich PCR were conducted to detect the repeats of NOTCH2NLC in a cohort of 1004 patients with neurodegenerative dementias from mainland China. As a result, 4 sporadic patients were found to carry the NOTCH2NLC repeats expansion, totally accounting for 0.4% of all dementia individuals, and the accurate repeated sizes were 110, 133,120 and 76 respectively. Of 4 mutation carriers, three and one were clinically diagnosed Alzheimer's disease (AD) and frontotemporal dementia (FTD) respectively. In addition, 3 out of them revealed leukoencephalopathy in T2-Flair imaging. This study revealed that although rare, the NOTCH2NLC repeat expansions may be associated with AD or FTD-like phenotype as well as leukoencephalopathy.