BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor that commonly occurs in children and adolescents under the age of 20. Dysregulation of microRNAs (miRNAs) is an important factor in the occurrence and progression of OS. MicroRNA miR-744-5p is aberrantly expressed in various tumors. However, its roles and molecular targets in OS remain unclear.
METHODS: Differentially expressed miRNAs in OS were analyzed using the Gene Expression Omnibus dataset GSE65071, and the potential hub miRNA was identified through weighted gene co-expression network analysis. Quantitative real-time PCR (qRT-PCR) was used to detect the expression of miR-744-5p in OS cell lines. In vitro experiments, including CCK-8 assays, colony formation assays, flow cytometry apoptosis assays, and tube formation assays, were performed to explore the effects of miR-744-5p on OS cell biological behaviors. The downstream target genes of miR-744-5p were predicted through bioinformatics, and the binding sites were validated by a dual-luciferase reporter assay.
RESULTS: The lowly expressed miRNA, miR-744-5p, was identified as a hub miRNA involved in OS progression through bioinformatic analysis. Nuclear factor I X (NFIX) was confirmed as a direct target for miR-744-5p in OS. In vitro studies revealed that overexpression of miR-744-5p could restrain the growth of OS cells, whereas miR-744-5p inhibition showed the opposite effect. It was also observed that treatment with the conditioned medium from miR-744-5p-overexpressed OS cells led to poorer proliferation and angiogenesis in human umbilical vein endothelial cells (HUVECs). Furthermore, NFIX overexpression restored the suppression effects of miR-744-5p overexpression on OS cell growth and HUVECs angiogenesis.
CONCLUSIONS: Our results indicated that miR-744-5p is a potential tumor-suppressive miRNA in OS progression by targeting NFIX to restrain the growth of OS cells and angiogenesis in HUVECs.

BACKGROUND: circRNA NFIX has been shown to exist as an oncogene in glioma. But its expression and role in NSCLC (non-small cell lung cancer) are still unclear. This research aimed to discover the expression and function of circRNA NFIX in NSCLC.
METHODS: In this research, qRT-PCR was utilized to investigate the expression levels of circRNA NFIX, miRNA-214-3p, and TRIAP1 in NSCLC tissues and cell lines. The binding sites between circRNA NFIX/TRIAP1 and miRNA-214-3p were predicted using the Starbase. These interactions were further validated using a double luciferase reporter assay. Cell proliferation and apoptosis were assessed through MTT and flow cytometry, respectively. The expression of apoptosis-related proteins was measured by western blot assay.
RESULTS: miRNA-214-3p could link with circRNA NFIX. circRNA NFIX was upregulated, while miRNA-214-3p was downregulated in NSCLC cell lines and clinical samples. Besides, suppression of circRNA NFIX repressed cell proliferation and induced apoptosis in NSCLC cells by upregulating miRNA-214-3p expression. Besides, the data indicated that TRIAP1 was a target of miRNA-214-3p, and it was negatively regulated by miRNA-214-3p in NSCLC cells. The excessive expression of miRNA-214-3p suppressed NSCLC cell proliferation and increased apoptosis. In addition, overexpression of TRIAP1 significantly reversed the effects on NSCLC cells caused by miRNA-214-3p mimic.
CONCLUSIONS: circRNA NFIX silencing repressed the proliferation of NSCLC cells and induced cell apoptosis by regulating the miR-214-3p/TRIAP1 axis, which was a potential diagnostic and therapeutic target for NSCLC.

Adenoid cystic carcinoma (AdCC) is a salivary gland neoplasm that infrequently appears in the sinonasal region. The aim of this study was to evaluate the outcome and clinicopathological parameters of sinonasal AdCC. A retrospective analysis was conducted on all cases of AdCC affecting the nasal cavity or paranasal sinuses between 2000 and 2018 at the University Hospital Zurich. Tumor material was examined for morphological features and analyzed for molecular alterations. A total of 14 patients were included. Mean age at presentation was 57.7 years. Sequencing revealed MYB::NFIB gene fusion in 11/12 analyzable cases. Poor prognostic factors were solid variant (p < 0.001), histopathological high-grade transformation (p < 0.001), and tumor involvement of the sphenoid sinus (p = 0.02). The median recurrence-free survival (RFS) and OS were 5.2 years and 11.3 years. The RFS rates at 1-, 5-, and 10-year were 100%, 53.8%, and 23.1%. The OS rates at 1-, 5-, and 10- years were 100%, 91.7%, and 62.9%, respectively. In Conclusion, the solid variant (solid portion > 30%), high-grade transformation, and sphenoid sinus involvement are negative prognostic factors for sinonasal AdCC. A high prevalence of MYB::NFIB gene fusion may help to correctly classify diagnostically challenging (e.g. metatypical) cases.

The adverse impacts of chronic hypoxia on maternal and infant health at high altitudes warrant significant attention. However, effective protective measures against the resultant growth restrictions and neurodevelopmental disorders in infants and young children are still lacking. This study investigated the neurodevelopment of mice offspring under hypoxic conditions by exposing pregnant mice to a hypobaric oxygen chamber that simulated the hypobaric hypoxia at an altitude of 4000 m until 28 days after delivery. Our findings suggested that prolonged exposure to hypoxia might result in emotional abnormalities and social disorders in offspring. The significant reduction in astrogliogenesis was a characteristic feature associated with neurodevelopmental disorders induced by hypoxia. Further studies demonstrated that cold-induced RNA-binding protein (CIRBP) was a key transcriptional regulator in astrogliogenesis, which downregulated astrocytic differentiation under hypoxia through its crosstalk with the NFIA. Our study emphasized the crucial role of CIRBP in regulating astrogliogenesis and highlighted its potential as a promising target for therapeutic interventions in neurodevelopmental disorders associated with hypoxia.

This article reports on the clinical and genetic characteristics of monozygotic twins with Marshall-Smith syndrome (MRSHSS) due to a mutation in the NFIX gene, along with a review of related literature. Both patients presented with global developmental delays, a prominent forehead, shallow eye sockets, and pectus excavatum. Genetic testing revealed a heterozygous splicing site mutation c.697+1G>A in both children, with parents showing wild-type at this locus. According to the guidelines of the American College of Medical Genetics and Genomics, this mutation is considered likely pathogenic and has not been previously reported in the literature. A review of the literature identified 32 MRSHSS patients with splicing/frameshift mutations. Accelerated bone maturation and moderate to severe global developmental delay/intellectual disability are the primary clinical manifestations of patients with MRSHSS. Genetic testing results are crucial for the diagnosis of this condition.
该文报道了一对NFIX基因变异导致Marshall-Smith综合征（Marshall-Smith syndrome, MRSHSS）的同卵双胞胎临床及遗传学特点并对相关文献进行复习。2例患儿均表现为全面发育落后、高额头、浅眼眶、漏斗胸。基因检测提示2例患儿均存在NFIX杂合剪接位点变异c.697+1G>A，父母该位点为野生型，根据美国医学遗传学与基因组学学会指南判定为可能致病性变异，该位点突变既往未见文献报道。复习文献共发现32例MRSHSS患者，突变类型为剪切/移码突变。骨骼成熟加速、中至重度全面发育迟缓/智力障碍是MRSHSS患者最主要的临床表现。基因检测结果是该病重要的诊断依据。.

Generation of neurons through direct reprogramming has emerged as a promising therapeutic approach for treating neurodegenerative diseases. In this study, we present an efficient method for reprogramming retinal glial cells into neurons. By suppressing Notch signaling by disrupting either Rbpj or Notch1/2, we induced mature Müller glial cells to reprogram into bipolar- and amacrine-like neurons. We demonstrate that Rbpj directly activates both Notch effector genes and genes specific to mature Müller glia while indirectly repressing expression of neurogenic basic helix-loop-helix (bHLH) factors. Combined loss of function of Rbpj and Nfia/b/x resulted in conversion of nearly all Müller glia to neurons. Last, inducing Müller glial proliferation by overexpression of dominant-active Yap promotes neurogenesis in both Rbpj- and Nfia/b/x/Rbpj-deficient Müller glia. These findings demonstrate that Notch signaling and NFI factors act in parallel to inhibit neurogenic competence in mammalian Müller glia and help clarify potential strategies for regenerative therapies aimed at treating retinal dystrophies.

Erythroid sarcoma (ES) is exceedingly rare in the pediatric population with only a handful of reports of de novo cases, mostly occurring in the central nervous system (CNS) or orbit. It is clinically and pathologically challenging and can masquerade as a nonhematopoietic small round blue cell tumor. Clinical presentation of ES without bone marrow involvement makes diagnosis particularly difficult. We describe a 22-month-old female with ES who presented with a 2-cm mass involving the left parotid region and CNS. The presence of crush/fixation artifact from the initial biopsy made definitive classification of this highly proliferative and malignant neoplasm challenging despite an extensive immunohistochemical workup. Molecular studies including RNA-sequencing revealed a NFIA::CBFA2T3 fusion. This fusion has been identified in several cases of de novo acute erythroid leukemia (AEL) and gene expression analysis comparing this case to other AELs revealed a similar transcriptional profile. Given the diagnostically challenging nature of this tumor, clinical RNA-sequencing was essential for establishing a diagnosis.

Glioblastoma is a rare and deadly malignancy with a low survival rate. Emerging evidence has shown that aberrantly expressed circular RNAs (circRNAs) play a critical role in the initiation and progression of GBM tumorigenesis. The oncogenic function of circZNF609 and circNFIX is involved in several types of cancer, but the role and underlying mechanism of these circRNAs in glioblastoma remain unclear. In this study, we hypothesized that circZNF609 and circNFIX may regulate EGFR through sponging miR-145-5p. Herein, we assessed the expression levels of circZNF609, circNFIX, miR-145-5p, and EGFR using quantitative polymerase chain reaction in glioblastoma patients and normal brain samples. The results showed that circZNF609, circNFIX, and EGFR expression levels were upregulated and miR145-5p was downregulated (p = 0.001, 0.06, 0.002, and 0.0065, respectively), while there was no significant association between clinicopathological features of the patients and the level of these genes expression. We also found a significant inverse correlation between miR145-5p and the expression of cZNF609, cNFIX and EGFR (p = 0.0003, 0.0006, and 0.009, respectively). These findings may open a new window for researchers to better understand the potential pathways involved in GBM pathogenesis. In conclusion, it may provide a new potential pathway for the development of effective drugs for the treatment of GBM patients.

As cellular transcription factors and DNA replicators, nuclear factor I (NFI) family members play an important role in mammalian development. However, there is still a lack of research on the muscle regeneration of NFI family members in cattle. In this study, the analysis of NFI family factors was conducted on their characterization, phylogenetics, and functional domains. We found that NFI family members were relatively conserved among different species, but there was heterogeneity in amino acid sequences, DNA coding sequences, and functional domain among members. Furthermore, among NFI family factors, we observed that NFIC exhibited highly expression in bovine muscle tissues, particularly influencing the expression of proliferation marker genes in myoblasts. To investigate the influence of NFIC on myoblast proliferation, we knocked down NFIC (si-NFIC) and found that the proliferation of myoblasts was significantly promoted. In terms of regulation mechanism, we identified that si-NFIC could counteract the inhibitory effect of the cell cycle inhibitor RO-3306. Interestingly, CENPF, as the downstream target gene of NFIC, could affect the expression of CDK1, CCNB1, and actively regulate the cell cycle pathway and cell proliferation. In addition, when CENPF was knocked down, the phosphorylation of p53 and the expression of Bax were increased, but the expression of Bcl2 was inhibited. Our findings mainly highlight the mechanism by which NFIC acts on the CENPF/CDK1 axis to regulate the proliferation of bovine myoblasts.

Neural stem cells (NSCs) are multipotent and correct fate determination is crucial to guarantee brain formation and homeostasis. How NSCs are instructed to generate neuronal or glial progeny is not well understood. Here, we addressed how murine adult hippocampal NSC fate is regulated and described how scaffold attachment factor B (SAFB) blocks oligodendrocyte production to enable neuron generation. We found that SAFB prevents NSC expression of the transcription factor nuclear factor I/B (NFIB) by binding to sequences in the Nfib mRNA and enhancing Drosha-dependent cleavage of the transcripts. We show that increasing SAFB expression prevents oligodendrocyte production by multipotent adult NSCs, and conditional deletion of Safb increases NFIB expression and oligodendrocyte formation in the adult hippocampus. Our results provide novel insights into a mechanism that controls Drosha functions for selective regulation of NSC fate by modulating the post-transcriptional destabilization of Nfib mRNA in a lineage-specific manner.