PTEN decreases NR2F1 expression to inhibit ciliogenesis during EGFRL858R-induced lung cancer progression.

Lung cancer is the major cause of death worldwide. Activation of oncogenes or inhibition of tumor suppressors causes cancer formation. Previous studies have indicated that PTEN, as a tumor suppressor, inhibits cancer formation. In this study, we studied the role of PTEN in EGFRL858R-induced lung cancer in vivo. Interestingly, loss of PTEN increased bronchial cell hyperplasia but decreased alveolar cell hyperplasia in EGFRL858R*PTEN-/--induced lung cancer. Systematic analysis of gene expression by RNA-seq showed that several genes related to ciliogenesis were upregulated in EGFRL858R*PTEN-/--induced lung cancer and subsequently showed that bronchial ciliated cells were hyperplastic. Several critical ciliogenesis-related genes, such as Mucin5A, DNAI2, and DNAI3, were found to be regulated by NR2F1. Next, NR2F1 was found to be inhibited by overexpression of PTEN, indicating that PTEN negatively regulates NR2F1, thereby inhibiting the expression of ciliogenesis-related genes and leading to the inhibition of bronchial cell hyperplasia during EGFRL858R-induced lung cancer progression. In addition, we also found that PTEN decreased AKT phosphorylation in A549, KRAS mutant, and H1299 cells but increased AKT phosphorylation in PC9, EGFRL858R, and H1299L858R cells, suggesting that PTEN may function as a tumor suppressor and an oncogene in lung cancers with KRAS mutation and EGFR mutation, respectively. PTEN acts as a double-edged sword that differentially regulates EGFRL858R-induced lung cancer progression in different genomic backgrounds. Understanding the PTEN in lung cancer with different genetic backgrounds will be beneficial for therapy in the future.

Infantile epileptic spasm syndrome as a new NR2F1 gene phenotype.

INTRODUCTION: NR2F1 pathogenetic variants are associated with the Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS). Recent studies indicate that BBSOAS patients not only have visual impairments but may also have developmental delays, hypotonia, thin corpus callosum and epileptic seizures. However, reports of BBSOAS occurrence along with infantile epileptic spasm syndrome (IESS) are rare. METHODS: Here, we report three cases involving children with IESS and BBSOAS caused by de novo NR2F1 pathogenetic variants and summarize the genotype, clinical characteristics, diagnosis and treatment of them. RESULTS: All three children experienced epileptic spasms and global developmental delays, with brain Magnetic Resonance Imaging (MRI) suggesting abnormalities (thinning of the corpus callosum or widened extracerebral spaces) and two of the children exhibiting abnormal visual evoked potentials. CONCLUSIONS: Our findings indicate that new missense NR2F1 pathogenetic variants may lead to IESS with abnormal visual evoked potentials. Thus, clinicians should be aware of the Bosch-Boonstra-Schaaf optic atrophy syndrome and regular monitoring of the fundus, and the optic nerve is necessary during follow-up.

NAT10-mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells via acetylating NR2F1 mRNA.

Cell fate determination in mammalian development is complex and precisely controlled and accumulating evidence indicates that epigenetic mechanisms are crucially involved. N4-acetylcytidine (ac4C) is a recently identified modification of messenger RNA (mRNA); however, its functions are still elusive in mammalian. Here, we show that N-acetyltransferase 10 (NAT10)-mediated ac4C modification promotes ectoderm differentiation of human embryonic stem cells (hESCs) by acetylating nuclear receptor subfamily 2 group F member 1 (NR2F1) mRNA to enhance translation efficiency (TE). Acetylated RNA immunoprecipitation sequencing (acRIP-seq) revealed that levels of ac4C modification were higher in ectodermal neuroepithelial progenitor (NEP) cells than in hESCs or mesoendoderm cells. In addition, integrated analysis of acRIP-seq and ribosome profiling sequencing revealed that NAT10 catalysed ac4C modification to improve TE in NEP cells. RIP-qRT-PCR analysis identified an interaction between NAT10 and NR2F1 mRNA in NEP cells and NR2F1 accelerated the nucleus-to-cytoplasm translocation of yes-associated protein 1, which contributed to ectodermal differentiation of hESCs. Collectively, these findings point out the novel regulatory role of ac4C modification in the early ectodermal differentiation of hESCs and will provide a new strategy for the treatment of neuroectodermal defects diseases.

[Analysis of NR2F1 gene variant in a child with optic atrophy and global developmental delay].

OBJECTIVE: To explore the genetic basis for a child with optic atrophy and global developmental delay. METHODS: A child who had presented at the Guangzhou Women and Children's Medical Center in January 2022 was selected as the study subject. Clinical data were collected. Whole exome sequencing (WES) was carried out for the child. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a nine-month-old female, had manifested dysopia and global developmental delay. Genetic testing revealed that she has harbored a de novo c.425G>C (p.Arg142Pro) variant of the NR2F1 gene, which has been associated with Bosch-Boonstra-Schaaf syndrome. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PS2+PM1+PM2_Supporting+PM5+PP3+PP4). CONCLUSION: The c.425G>C (p.Arg142Pro) variant of the NR2F1 gene probably underlay the pathogenesis in this child. Above finding has enriched the genotypic and phenotypic spectrum of the NR2F1 gene.

Lnc NR2F1-AS1 Promotes Breast Cancer Metastasis by Targeting the MiR-25-3p/ZEB2 Axis.

Background: Long noncoding RNAs (lncRNAs) substantially affect tumor metastasis and are aberrantly expressed in various cancers. However, its role in breast cancer (BC) remains unclear. Methods: A microarray assay of differentially expressed lncRNAs in epithelial-mesenchymal transition (EMT) and non-EMT cells was performed. The prognostic value of lnc NR2F1-AS1 expression in patients with BC was analyzed using The Cancer Genome Atlas database. Lnc NR2F1-AS1 expression levels in different BC cell lines were assessed using quantitative real-time PCR. The role of lnc NR2F1-AS1 in BC cell metastasis was investigated in vitro and in vivo. Dual luciferase reporter assay and RNA immunoprecipitation were performed to investigate the relationship between lnc NR2F1-AS1, miR-25-3p, and ZEB2. Results: High levels of lnc NR2F1-AS1 were observed in BC cells undergoing EMT and were closely correlated with adverse prognosis in patients with BC. Lnc NR2F1-AS1 knockdown significantly inhibited BC cell migration, invasiveness in vitro, and metastasis in vivo. Mechanistically, lnc NR2F1-AS1 competitively binds to miR-25-3p to impede ZEB2 degradation, a positive EMT transcription factor in BC. Conclusions: Our study revealed a novel lnc NR2F1-AS1/miR-25-3p/ZEB2 axis in BC metastasis and that lnc NR2F1-AS1 may serve as a potential therapeutic target for BC metastasis.

NR2F1 shapes mitochondria in the mouse brain, providing new insights into Bosch-Boonstra-Schaaf optic atrophy syndrome.

The nuclear receptor NR2F1 acts as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, mutations in the NR2F1 gene cause Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including vision impairment, intellectual disability and autistic traits. In this study, we identified, by genome-wide and in silico analyses, a set of nuclear-encoded mitochondrial genes as potential genomic targets under direct NR2F1 transcriptional control in neurons. By combining mouse genetic, neuroanatomical and imaging approaches, we demonstrated that conditional NR2F1 loss of function within the adult mouse hippocampal neurogenic niche results in a reduced mitochondrial mass associated with mitochondrial fragmentation and downregulation of key mitochondrial proteins in newborn neurons, the genesis, survival and functional integration of which are impaired. Importantly, we also found dysregulation of several nuclear-encoded mitochondrial genes and downregulation of key mitochondrial proteins in the brain of Nr2f1-heterozygous mice, a validated BBSOAS model. Our data point to an active role for NR2F1 in the mitochondrial gene expression regulatory network in neurons and support the involvement of mitochondrial dysfunction in BBSOAS pathogenesis.

NR2F1-AS1: A Functional Long Noncoding RNA in Tumorigenesis.

BACKGROUND: NR2F1-AS1 is a long non-coding RNA (lnc RNA) that is involved in different biological processes. It plays an integral role in the pathophysiology of human diseases, especially tumorigenesis and progression. Therefore, it may be a promising target for numerous tumor biotherapeutics. The current review study aimed to show the pathophysiological activities and processes of RNA NR2F1-AS1 in cancer cells. METHODS: The contents of the present review were based on information obtained from PubMed. In the data search, "NR2F1-AS1" was chosen as the first keyword, whereas "cancer" was chosen as the second keyword. This review selected and summarized studies published between 2019-2021, concerning the biological functions and mechanisms of NR2F1-AS1 in the development of tumorigenesis. RESULTS: It was found that NR2F1-AS1 regulates a variety of biological activities such as proliferation, invasion, migration, and apoptosis. It acts as an oncogene because it is abnormally expressed and promotes the progression of cancer in a variety of malignancies, including esophageal squamous cell carcinoma, non-small cell lung cancer, breast cancer, neuroblastoma, endometrial cancer, thyroid cancer, and gastric cancer. However, it was evident that NR2F1-AS1 inhibits the progression of cancer in cervical squamous cell carcinoma. CONCLUSION: NR2F1-AS1 is a potential new biomarker and therapeutic target for the treatment of different cancers.

Common Neuroimaging Findings in Bosch-Boonstra-Schaaf Optic Atrophy Syndrome.

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare autosomal dominant syndrome secondary to mutations in NR2F1 (COUP-TF1), characterized by visual impairment secondary to optic nerve hypoplasia and/or atrophy, developmental and cognitive delay, and seizures. This study reports common neuroimaging findings in a cohort of 21 individuals with BBSOAS that collectively suggest the diagnosis. These include mesial temporal dysgyria, perisylvian dysgyria, posterior predominant white matter volume loss, callosal abnormalities, lacrimal gland abnormalities, and optic nerve volume loss.

Spatial control of astrogenesis progression by cortical arealization genes.

Sizes of neuronal, astroglial and oligodendroglial complements forming the neonatal cerebral cortex largely depend on rates at which pallial stem cells give rise to lineage-committed progenitors and the latter ones progress to mature cell types. Here, we investigated the spatial articulation of pallial stem cells' (SCs) commitment to astrogenesis as well as the progression of committed astroglial progenitors (APs) to differentiated astrocytes, by clonal and kinetic profiling of pallial precursors. We found that caudal-medial (CM) SCs are more prone to astrogenesis than rostro-lateral (RL) ones, while RL-committed APs are more keen to proliferate than CM ones. Next, we assessed the control of these phenomena by 2 key transcription factor genes mastering regionalization of the early cortical primordium, Emx2 and Foxg1, via lentiviral somatic transgenesis, epistasis assays, and ad hoc rescue assays. We demonstrated that preferential CM SCs progression to astrogenesis is promoted by Emx2, mainly via Couptf1, Nfia, and Sox9 upregulation, while Foxg1 antagonizes such progression to some extent, likely via repression of Zbtb20. Finally, we showed that Foxg1 and Emx2 may be implicated-asymmetrically and antithetically-in shaping distinctive proliferative/differentiative behaviors displayed by APs in hippocampus and neocortex.

A fetus with Bosch-Boonstra-Schaaf optic atrophy syndrome characterized by bilateral ventricle widening: A case report and related literature review.

RATIONALE: Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare neurodevelopmental disorder caused by loss-of-function variants in the Nuclear Receptor Subfamily 2 Group F Member 1 (NR2F1). Here, we report a case of fetal BBSOAS. The fetus is typically featured by bilateral ventricle widening in the late second trimester, meanwhile, a 7.94-Mb deletion fragment on 5q14.3q15 involving the whole NR2F1 gene was confirmed by copy number variation sequencing (CNV-Seq) combined with karyotyping analysis. Our aim is to provide comprehensive prenatal clinical management strategy for fetal BBSOAS. PATIENT CONCERNS: A 29-year-old primipara and her husband were referred to our prenatal diagnosis center due to the widening of bilateral ventricles at 29 + 1 weeks of gestation age. DIAGNOSES: Ultrasound revealed the fetal widening posterior horns of bilateral ventricles at the GA of 27 + 3 weeks, 11 mm on the left and 10 mm on the right. At the following 29 + 1 weeks, ultrasound showed the posterior horn of the left lateral ventricle: 12 mm while the width of the right decreased to 9 mm, and intracranial arachnoid cyst. Furthermore, MRI confirmed that intracranial cyst might originate from an enlarged cisterna venae magnae cerebri, with mild dilation of 13.5 mm on the left ventricle. The fetal karyotyping analysis and CNV-Seq detection confirmed a 7.94-Mb deleted fragment on 5q14.3q15 (89340000_97280000) through the amniocentesis at 29 + 4 weeks of GA. INTERVENTIONS: The fetus was closely monitored and underwent the following assessment by the multidisciplinary team. OUTCOMES: The pregnancy was terminated in the end. LESSONS: It is vital to use molecular and cytogenetical detections combined with a dynamic development history to make a definite diagnosis and evaluate the genetic status for the fetuses with BBSOAS.

LncRNA NR2F1-AS1 Inhibits the Malignant Properties of Cervical Cancer Cells via Targeting miR-642a-3p/NR2F1 Axis.

Background: Cervical cancer (CC), as a serious menace to the health of women, has long been one of the most lethal gynecologic neoplasms throughout the world. Long non-coding RNA (LncRNA) NR2F1-AS1 has been documented to exert crucial functions in many malignant tumors. Nonetheless, the function and molecular mechanism of NR2F1-AS1 in CC remain completely unknown. Objectives: This study aimed to explore the function and molecular mechanism of NR2F1-AS1 in CC. Methods: The expression levels of NR2F1-AS1, miR-642a-3p, NR2F1 in CC tissues, and cell lines were examined by reverse transcription real-time quantitative polymerase chain reaction. Cell viability, proliferation, migration, and invasion were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, colony formation and Transwell assays. The protein levels of epithelial-mesenchymal transition markers and NR2F1 in CC cells were assessed by Western blot analysis. The correlations among NR2F1-AS1, miR-642a-3p, and NR2F1 were estimated through luciferase reporter and RNA immunoprecipitation assays. Results: NR2F1-AS1 expression was clearly downregulated in CC tissues and cell lines. Molecular mechanistic experiments showed that NR2F1-AS1 overexpression upregulated NR2F1 expression in CC cells by directly binding to miR-642a-3p, and inhibiting by this way cell viability, proliferation, migration, and invasion in CC. Rescue assays showed that NR2F1 knockdown or miR-642a-3p overexpression offset NR2F1-AS1 upregulation-induced inhibition on CC cell malignant phenotypes. Conclusions: These findings revealed that NR2F1-AS1 played a tumor suppressor role in CC by mediating the miR-642a-3p/NR2F1 axis.

Novel NR2F1 variant identified by whole-exome sequencing in a patient with Bosch-Boonstra-Schaaf optic atrophy syndrome.

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is an extremely rare autosomal dominant disorder characterized by intellectual disability, developmental delay, seizures, hypotonia, hearing loss, and optic nerve atrophy. This syndrome is caused by loss-of-function variants in the nuclear receptor subfamily 2 group F member 1 (NR2F1) gene. To date, approximately 80 patients have been reported with BBSOAS. Here, we describe a 3-year-old infant with delayed development, intellectual disability, strabismus, nystagmus, and optic atrophy with well-characterized features associated with BBSOAS. Whole-exome sequencing revealed a novel heterozygous missense mutation (NM_005654.6:c.437G>A, p.Cys146Tyr) in the NR2F1 gene. This missense variant is predicted to be deleterious by the protein prediction tools (SIFT, PolyPhen-2, and MutationTaster). To the best of our knowledge, this is the first patient with BBSOAS reported from Turkey.

The emerging role of NR2F1-AS1 in the tumorigenesis and progression of human cancer.

Long noncoding RNAs (lncRNAs) are transcripts of more than 200 nucleotides that lack the ability to encode protein. Convincing studies have indicated that lncRNAs can act as oncogenes or tumor suppressors by regulating gene expression. The novel lncRNA NR2F1-AS1 was recently found to be abnormally expressed in various malignancies, including hepatocellular carcinoma, gastric cancer, colorectal cancer, pancreatic cancer, breast cancer, lung cancer, thyroid cancer, esophageal squamous cell carcinoma, osteosarcoma, and neuroblastoma. NR2F1-AS1 can modify cell proliferation, invasion, migration, apoptosis, the cell cycle, and glycolysis through various mechanisms involving direct or indirect effects on pathways. Furthermore, NR2F1-AS1 may be a potential therapeutic target and prognostic marker in cancer, as it has been related to the clinicopathological characteristics of cancer patients. Here, we summarize and clarify recent research advances regarding the expression, function, molecular mechanisms, and clinical implications of NR2F1-AS1 in multiple malignant tumors.

NR2F1 Is a Barrier to Dissemination of Early-Stage Breast Cancer Cells.

Cancer cells can disseminate during very early and sometimes asymptomatic stages of tumor progression. Though biological barriers to tumorigenesis have been identified and characterized, the mechanisms that limit early dissemination remain largely unknown. We report here that the orphan nuclear receptor nuclear receptor subfamily 2, group F, member 1 (NR2F1)/COUP-TF1 serves as a barrier to early dissemination. NR2F1 expression was decreased in patient ductal carcinoma in situ (DCIS) samples. High-resolution intravital imaging of HER2+ early-stage cancer cells revealed that loss of function of NR2F1 increased in vivo dissemination and was accompanied by decreased E-cadherin expression, activation of wingless-type MMTV integration site family, member 1 (WNT)-dependent ß-catenin signaling, disorganized laminin 5 deposition, and increased expression of epithelial-mesenchymal transition (EMT) genes such as twist basic helix-loop-helix transcription factor 1 (TWIST1), zinc finger E-box binding homeobox 1 (ZEB1), and paired related homeobox 1 (PRRX1). Furthermore, downregulation of NR2F1 promoted a hybrid luminal/basal phenotype. NR2F1 expression was positively regulated by p38α signaling and repressed by HER2 and WNT4 pathways. Finally, early cancer cells with NR2F1LOW/PRRX1HIGH staining were observed in DCIS samples. Together, these findings reveal the existence of an inhibitory mechanism of dissemination regulated by NR2F1 in early-stage breast cancer cells. SIGNIFICANCE: During early stages of breast cancer progression, HER2-mediated suppression of NR2F1 promotes dissemination by inducing EMT and a hybrid luminal/basal-like program.

Hypoxia-induced long noncoding RNA NR2F1-AS1 maintains pancreatic cancer proliferation, migration, and invasion by activating the NR2F1/AKT/mTOR axis.

Accumulating evidence has demonstrated the essential role of long noncoding RNAs (lncRNAs) in various types of human cancer, including pancreatic cancer (PC). However, the functions and regulatory mechanisms of nuclear receptor subfamily 2 group F member 1 antisense RNA 1 (NR2F1-AS1) that are responsible for its role in the malignant progression of PC cells remains to be investigated. In this study, the biological effects of NR2F1-AS1 and NR2F1 in PC were investigated by in vitro and in vivo experiments. The mechanisms of NR2F1-AS1 were monitored by bioinformatic predictive analysis and confirmatory experiments. Our results indicated that NR2F1-AS1 was overexpressed and positively correlated with poor survival in PC. Depletion of NR2F1-AS1 restrained PC cell proliferation, migration, invasion, and suppressed xenograft tumor growth and metastasis in vitro and in vivo. Mechanistic experiments suggested that NR2F1-AS1 positively regulated the neighboring NR2F1 gene, which subsequently activated AKT/mTOR signaling, resulting in the upregulation of hypoxia-inducible factor-1α (HIF-1α). Further investigations elucidated that NR2F1-AS1 expression was transcriptionally regulated by HIF-1α under hypoxia. These findings demonstrated that hypoxia-induced NR2F1-AS1 expression directly increased NR2F1 levels to promote PC cell proliferation, migration, and invasion by activating AKT/mTOR signaling. Together, these findings suggest that NR2F1-AS1 could be a prospective therapeutic target for PC.

ZEB1-regulated lnc-Nr2f1 promotes the migration and invasion of lung adenocarcinoma cells.

Numerous long non-coding RNAs (lncRNAs) are differentially expressed in cancer cells compared with normal cells and are involved in tumor progression and metastasis. Metastasis is initiated by the epithelial-to-mesenchymal transition (EMT) process, which can also be regulated by lncRNAs. Given that ZEB1 is an important transcription factor inducing EMT, we screened lncRNAs controlled by ZEB1 using RNA sequencing in murine lung adenocarcinoma cells. Among several lncRNAs regulated by ZEB1, we selected lnc-Nr2f1. Lnc-Nr2f1 is upregulated by ZEB1 and TGF-ß, a potent EMT signal. Growth, migration, and invasion of lung adenocarcinoma cells were decreased after lnc-Nr2f1 knockdown and increased after lnc-Nr2f1 overexpression. Interestingly, lnc-Nr2f1 was transcriptionally controlled by NR2F1, a transcription factor that is transcribed in the antisense direction. NR2F1 was also upregulated and positively correlated with ZEB1, forming a ZEB1/NR2F1/lnc-Nr2f1 axis. Lnc-Nr2f1, in turn, promoted Twist2 transcription through direct binding to its genomic DNA region. Collectively, lnc-Nr2f1 was upregulated by ZEB1 and NR2F1, and promoted migration and invasion of lung adenocarcinoma cells via TWIST2 regulation.

The EMT-induced lncRNA NR2F1-AS1 positively modulates NR2F1 expression and drives gastric cancer via miR-29a-3p/VAMP7 axis.

Deregulated lncRNAs play critical roles in tumorigenesis and tumor progression. NR2F1-AS1 is an antisense lncRNA of NR2F1. However, the biological function of NR2F1-AS1 in gastric cancer (GC) remains largely unclear. In this study, we revealed that NR2F1-AS1 and NR2F1 were both positively correlated with the degree of malignancy and predicted poor prognosis in two independent GC cohorts. Besides, NR2F1-AS1 and NR2F1 can respond to Epithelial-to-mesenchymal transition (EMT) signaling in GC, since their expression was increased by TGF-beta treatment and decreased after stable overexpression of OVOL2 in GC cell lines. NR2F1-AS1 and NR2F1 were highly co-expressed in pan-tissues and pan-cancers. Depletion of NR2F1-AS1 compromised the expression level of NR2F1 in GC cells. Furthermore, NR2F1-AS1 knockdown inhibited the proliferation, migration, invasion and G1/S transition of GC cells. More importantly, transcriptome sequencing revealed a novel ceRNA network composed of NR2F1-AS1, miR-29a-3p, and VAMP7 in GC. The overexpression of VAMP7 predicted poor prognosis in GC. Rescue assay confirmed that NR2F1-AS1 promotes GC progression through miR-29a-3p/VAMP7 axis. Our finding highlights that the aberrant expression of NR2F1-AS1 is probably due to the abnormal EMT signaling in GC. LncRNA NR2F1-AS1 plays crucial roles in GC progression by modulating miR-29a-3p/VAMP7 axis, suggesting that NR2F1-AS1 may serve as a potential therapeutic target in GC.

NR2F1-AS1 Acts as an Oncogene in Breast Cancer by Competitively Binding with miR-641.

BACKGROUND: Long noncoding RNA (lncRNA) NR2F1-AS1 has been previously reported to be dysregulated in human cancers and implicated in the tumorigenesis and development of tumors. In this research, we detected the expression level and biological function of NR2F1-AS1 in breast cancer (BC). METHODS: The expression of NR2F1-AS1 in BC tissues and cell lines was determined by qRT-PCR analysis. The associations of NR2F1-AS1 expression with clinical characteristics and survival rate of BC patients were also analyzed. Cell proliferation, migration, and invasion were measured by the CCK-8 and Transwell assay. RESULTS: The results revealed that the total survival time of BC patients with high NR2F1-AS1 expression was lower than that of BC patients with low NR2F1-AS1 expression. Moreover, functional experiments demonstrated that knockdown of NR2F1-AS1 inhibited BC cell viability, migration, and invasion abilities, whereas overexpression of NR2F1-AS1 had the opposite effect. Mechanistic investigation revealed that NR2F1-AS1 can competitively bind with microRNA-641 (miR-641) in BC. These results revealed that NR2F1-AS1 functioned as an oncogene by sponging miR-641 expression in BC cell progression. Moreover, miR-641 was negatively correlated with NR2F1-AS1 in BC tissues. CONCLUSION: Hence, NR2F1-AS1 was found to act as an oncogene in breast cancer by suppressing miR-641. We suggested that NR2F1-AS1 could be a potential biomarker for BC diagnosis and therapy.

Regulation of axial elongation by Cdx.

The primordia of the post-otic mouse embryo forms largely from a bipotential cell population containing neuromesodermal progenitors (NMP) which reside in the tail bud and contribute to the elaboration of the major body axis after gastrulation. The mechanisms by which the NMP population is both maintained and subsequently directed down mesodermal and neural lineages is incompletely understood. The vertebrate transcription factor Cdx2, is essential for axial elongation and has been implicated in maintaining the NMP niche and in specification of NMP derivatives. To better understand the role of the Cdx family in axial elongation, we employed a conditional mutant allele which evokes total loss of Cdx function, and enriched for tail bud progenitors through the use of a Pax2-GFP transgenic reporter. Using this approach, we identified 349 Cdx-dependent genes by RNA sequencing (RNA-seq). From these, Gene Ontology and chromatin immunoprecipitation analysis further revealed a number of putative direct Cdx candidate target genes implicated in axial elongation, including Sp8, Isl1, Evx1, Zic3 and Nr2f1. Additional analysis of available single-cell RNA-seq data from mouse tail buds revealed the co-expression of Sp8, Isl1, Evx1 and Zic3 with Cdx2 in putative NMP cells, while Nr2f1 was excluded from this population. These findings identify a number of novel Cdx targets and provide further insight into the critical roles for Cdx in elaborating the post-otic embryo.

A severe case of Bosch-Boonstra-Schaaf optic atrophy syndrome with a novel description of coloboma and septo-optic dysplasia, owing to a start codon variant in the NR2F1 gene.

Bosch-Boonstra-Schaaf optic atrophy syndrome (BBSOAS) is a rare congenital syndrome characterized by a range of phenotypes including optic atrophy and intellectual disability among other features. Pathogenic variants in the NR2F1 (nuclear receptor subfamily 2 group F member 1) gene have been linked to this condition. A recent report has shown that pathogenic variants in the start codon lead to decreased expression of the NR2F1 protein and a relatively mild phenotype, similar to that seen in whole gene deletions, and due to the lack of the dominant negative effect. Here we describe a severe case of BBSOAS with an initiation codon missense variant. The developmental delay, seizures, optic atrophy are in keeping with features observed in this condition, however this is the first report to describe colobomas and septo-optic dysplasia as associated features potentially extending the phenotype linked to BBSOAS. In addition, this is the first description of a severe phenotype linked to a de novo missense variant in the start codon of the NR2F1 gene.