NR2F1 regulates regional progenitor dynamics in the mouse neocortex and cortical gyrification in BBSOAS patients
EMBO JOURNAL
Authors: Bertacchi, Michele; Romano, Anna Lisa; Loubat, Agnes; Mau-Them, Frederic Tran; Willems, Marjolaine; Faivre, Laurence; van Kien, Philippe Khau; Perrin, Laurence; Devillard, Francoise; Sorlin, Arthur; Kuentz, Paul; Philippe, Christophe; Garde, Aurore; Neri, Francesco; Di Giaimo, Rossella; Oliviero, Salvatore; Cappello, Silvia; D'Incerti, Ludovico; Frassoni, Carolina; Studer, Michele
Abstract
The relationships between impaired cortical development and consequent malformations in neurodevelopmental disorders, as well as the genes implicated in these processes, are not fully elucidated to date. In this study, we report six novel cases of patients affected by BBSOAS (Boonstra-Bosch-Schaff optic atrophy syndrome), a newly emerging rare neurodevelopmental disorder, caused by loss-of-function mutations of the transcriptional regulator NR2F1. Young patients with NR2F1 haploinsufficiency display mild to moderate intellectual disability and show reproducible polymicrogyria-like brain malformations in the parietal and occipital cortex. Using a recently established BBSOAS mouse model, we found that Nr2f1 regionally controls long-term self-renewal of neural progenitor cells via modulation of cell cycle genes and key cortical development master genes, such as Pax6. In the human fetal cortex, distinct NR2F1 expression levels encompass gyri and sulci and correlate with local degrees of neurogenic activity. In addition, reduced NR2F1 levels in cerebral organoids affect neurogenesis and PAX6 expression. We propose NR2F1 as an area-specific regulator of mouse and human brain morphology and a novel causative gene of abnormal gyrification.
LncRNA NR2F1-AS1 Regulates miR-371a-3p/TOB1 Axis to Suppress the Proliferation of Colorectal Cancer Cells
CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS
Authors: Wang, Jianguang; Dong, Shuaijun; Zhang, Jianfeng; Jing, Dongshuai; Wang, Wenqiang; Dong, Lujia; Zhao, Yuanzhen
Abstract
A recent study reported the oncogenic function of lncRNA NR2F1-AS1 in liver cancer. Interestingly, by analyzing TCGA data set, the downregulation of NR2F1-AS1 in colorectal cancer (CRC) was observed. This observation triggered interest to analyze the functions of NR2F1-AS1 in CRC. It was observed that NR2F1-AS1 was downregulated in CRC and predicted poor survival. NR2F1-AS1 can directly interact with miR-371a-3p but their overexpression failed to affect the expression of each other. However, NR2F1-AS1 overexpression led to the upregulation of TOB1, a target of miR-371a-3p. Cell proliferation analysis revealed reduced proliferation rate of CRC cells after NR2F1-AS1 and TOB1 overexpression. MiR-371a-3p overexpression played an opposite role and reduced the effects of NR2F1-AS1 and TOB1 overexpression. In conclusion, NR2F1-AS1 regulates miR-371a-3p/TOB1 axis to suppress the proliferation of CRC cells.
COA
Publication 
Loading ......
