Inhibitory Effect of MicroRNA-376b-Overexpressing Bone Marrow Mesenchymal Stem Cells (BMSCs) on Malignant Characteristics of Glioma Cells Through Targeting Forkhead Box Protein P2 (FOXP2)

This study investigated the impact of microRNA (miR)-376b derived from BMSCs on glioma progression. BMSCs were transfected with miR-376b mimic, miR-376b inhibitor or NC and then cocultured with glioma cells followed by measuring cell behaviors by MTT assay, Transwell assay and flow cytometry, FOXP2 and miR-376b expression by Western blot and RT-qPCR. After confirming the inhibitory and mimicking activity of transfection, we found that overexpression of miR-376b in BMSCs decreased glioma cell invasion, migration and proliferation but promoted cell apoptosis within 24 h and 48 h after transfection along with reduced number of cells in S-phase. Mechanically, miR-376b targeted miR-376b and up-regulation of miR-376b caused down-regulation of FOXP2 (p < 0.05). Overexpression of miR-376b in BMSCs decelerated glioma cell cycle and inhibitedmalignant behaviors of glioma cells by targeting FOXP2 expression. These evidence unveils the potential role of FOXP2 as a biomarker for the treatment of gliomas.

MiRNA-335 Modulates Hepatoma Cell Lines Apoptosis and Proliferation by Targeting Forkhead Box O3a (FOXO3a)

This study intends to elucidate MiRNA-335’s role in hepatoma cell lines (HCC). Real-time PCR was used to detect MiRNA-335 expression in HCC, flow cytometry and MTT were used to detect apoptosis and proliferation. Luciferase reporting system analyzed the targeting relationship between Foxo3a and MiRNA-335. HCC (SMMC7721 cell) exhibited significantly reduced MiRNA-335 compared to normal hepatocyte cell (HL7702). MiRNA-335 mimic inhibited HCC proliferation and enhanced apoptosis, which were reversed by MiRNA-335 inhibitor. Luciferase reporter gene system showed that MiRNA-335 significantly inhibited the fluorescent activity of Foxo3a 3′-UTR, indicating that MiRNA-335 could target Foxo3a RNA. In conclusion, the decrease of MiRNA-335 can promote the proliferation of hepatoma cells and inhibit apoptosis possibly through regulating Foxo3a, which provides a new direction for the treatment of liver cancer.

Exosomal MicroRNA-325 Enhances Trophoblast Migration and Invasion Through Downregulation of Lethal-7b and Upregulation of Forkhead Box Protein O1 Expression in Preeclampsia

We aimed to explore the mechanism by how microRNA (miRNA)-325 derived from marrow mesenchymal stem cell exosomes (MSC-exos) affects the trophoblast progression in preeclampsia (PE). RT-qPCR detected the level of miRNA let-7b and FOXO1 in the placenta tissue of PE patients. Functional experiment was performed to analyze the effect of FOXO1 inhibitor and let-7b mimics on cell migration, invasion and apoptosis through Transwell assay and TUNEL staining. The trophoblast cell was co-cultured with overexpressed-miR-325 MSC-exos to measure gene expression and cell progression. let-7b was highly and FOXO1 was lowly expressed in PE placenta tissue. let-7b directly targeted and inhibited FOXO1 expression. Importantly, as miR-325 was internalized by trophoblast cells through MSC-exos, MSC-exos overexpressing miR-325 inhibited let-7b expression in trophoblasts, up-regulated FOXO1 and activated AKT signaling pathway. Further, MSC-exos treatment promoted invasion and migration of trophoblast cell and inhibited apoptosis. In conclusion, miR-325 derived from MSC-exos promotes the invasion and migration of trophoblast cells in PE through inhibition of let7b and upregulation of FOXO1.

Paving Therapeutic Avenues for FOXG1 Syndrome: Untangling Genotypes and Phenotypes from a Molecular Perspective

Development of the central nervous system (CNS) depends on accurate spatiotemporal control of signaling pathways and transcriptional programs. Forkhead Box G1 (FOXG1) is one of the master regulators that play fundamental roles in forebrain development; from the timing of neurogenesis, to the patterning of the cerebral cortex. Mutations in the FOXG1 gene cause a rare neurodevelopmental disorder called FOXG1 syndrome, also known as congenital form of Rett syndrome. Patients presenting with FOXG1 syndrome manifest a spectrum of phenotypes, ranging from severe cognitive dysfunction and microcephaly to social withdrawal and communication deficits, with varying severities. To develop and improve therapeutic interventions, there has been considerable progress towards unravelling the multi-faceted functions of FOXG1 in the neurodevelopment and pathogenesis of FOXG1 syndrome. Moreover, recent advances in genome editing and stem cell technologies, as well as the increased yield of information from high throughput omics, have opened promising and important new avenues in FOXG1 research. In this review, we provide a summary of the clinical features and emerging molecular mechanisms underlying FOXG1 syndrome, and explore disease-modelling approaches in animals and human-based systems, to highlight the prospects of research and possible clinical interventions.

The Clinical Significance of Forkhead Box M1 in Esophageal Squamous Cell Carcinoma Tissues: A Study Based on In-house Immunohistochemistry, RNA-sequencing, and Data Mining

BackgroundEsophageal squamous cell carcinoma (ESCC) ranks the sixth in mortality rates in cancers due to a lack of a specific target of diagnosis and treatment in the early stages. Although Forkhead box M1 (FOXM1) has been reported to be differentially expressed in ESCC, its clinical role and function in ESCC remained unclarified.MethodsData from our hospital and public databases (n = 1906) were combined to estimate how FOXM1 overexpression showed its discriminatory ability between ESCC and non-ESCC esophageal tissues. Downstream targets of FOXM1 were predicted by using Cistrome database. Functional enrichment analyses were performed to explore the potential signaling pathways related to FOXM1 in ESCC. Based on the available clinical parameters, we investigated the prognosis potential of FOXM1 and its targets.ResultsThe pooled standard mean difference (SMD) for FOXM1 is 2.62 (95% CI: 2.08–3.16), indicating that FOXM1 is upregulated in ESCC. FOXM1 has an extremely high discrimination potential in ESCC because the area under the curve (AUC) of the summary receiver operating characteristic curve (sROC) is 0.99 (95% CI: 0.97–0.99). A total of 168 downstream targets were identified, and nine hub genes were screened from them. We found that FOXM1 and its targets were significantly enriched in the cell cycle. Additionally, the correlation between FOXM1 and clinical parameters had not been observed, except for age.ConclusionsFOXM1 is upregulated in ESCC and has an extremely high discrimination potential in ESCC.