Applications of gastric peroral endoscopic myotomy in the treatment of upper gastrointestinal tract disease.

Gastric peroral endoscopic myotomy (G-POME) is an emerging minimally invasive endoscopic technique involving the establishment of a submucosal tunnel around the pyloric sphincter. In 2013, Khashab et al used G-POME for the first time in the treatment of gastroparesis with enhanced therapeutic efficacy, providing a new direction for the treatment of gastroparesis. With the recent and rapid development of G-POME therapy technology, progress has been made in the treatment of gastroparesis and other upper digestive tract diseases, such as congenital hypertrophic pyloric stenosis and gastric sleeve stricture, with G-POME. This article reviews the research progress and future prospects of G-POME for the treatment of upper digestive tract gastrointestinal diseases.

miR-6076 targets BCL6 in SH-SY5Y cells to regulate amyloid-ß-induced neuronal damage.

Amyloid-ß1-42 (Aß1-42 ) is strongly associated with Alzheimer's disease (AD). The aim of this study is to elucidate whether and how miR-6076 participates in the modulation of amyloid-ß (Aß)-induced neuronal damage. To construct the neuronal damage model, SH-SY5Y cells were treated with Aß1-42 . By qRT-PCR, we found that miR-6076 is significantly upregulated in Aß1-42 -treated SH-SY5Y cells. After miR-6076 inhibition, p-Tau and apoptosis levels were downregulated, and cell viability was increased. Through online bioinformatics analysis, we found that B-cell lymphoma 6 (BCL6) was a directly target of miR-6076 via dual-luciferase reporter assay. BCL6 overexpression mediated the decrease in elevated p-Tau levels and increased viability in SH-SY5Y cells following Aß1-42 treatment. Our results suggest that down-regulation of miR-6076 could attenuate Aß1-42 -induced neuronal damage by targeting BCL6, which provided a possible target to pursue for prevention and treatment of Aß-induced neuronal damage in AD.

Lama2 And Samsn1 Mediate the Effects of Brn4 on Hippocampal Neural Stem Cell Proliferation and Differentiation.

The transcription factor Brn4 exhibits vital roles in the embryonic development of the neural tube, inner ear, pancreas islet, and neural stem cell differentiation. Our previous studies have shown that Brn4 promotes neuronal differentiation of hippocampal neural stem cells (NSCs). However, its mechanism is still unclear. Here, starting from the overlapping genes between RNA-seq and ChIP-seq results, we explored the downstream target genes that mediate Brn4-induced hippocampal neurogenesis. There were 16 genes at the intersection of RNA-seq and ChIP-seq, among which the Lama2 and Samsn1 levels can be upregulated by Brn4, and the combination between their promoters and Brn4 was further determined using ChIP and dual luciferase reporter gene assays. EdU incorporation, cell cycle analysis, and CCK-8 assay indicated that Lama2 and Samsn1 mediated the inhibitory effect of Brn4 on the proliferation of hippocampal NSCs. Immunofluorescence staining, RT-qPCR, and Western blot suggested that Lama2 and Samsn1 mediated the promoting effect of Brn4 on the differentiation of hippocampal NSCs into neurons. In conclusion, our study demonstrates that Brn4 binds to the promoters of Lama2 and Samsn1, and they partially mediate the regulation of Brn4 on the proliferation inhibition and neuronal differentiation promotion of hippocampal NSCs.

miR-6216 regulates neural stem cell proliferation by targeting RAB6B.

Neural stem cells (NSCs) are a class of self-renewing, multipotent and undifferentiated progenitor cells that retain the capacity to both glial and neuronal lineages. MicroRNAs (miRNAs) are small non-coding RNAs that play an important role in stem cell fate determination and self-renewal. Our previous RNA-seq data indicated that the expression of miR-6216 was decreased in denervated hippocampal exosomes compared with normal. However, whether miR-6216 participates in regulating NSC function remains to be elucidated. In this study, we demonstrated that miR-6216 negatively regulates RAB6B expression. Forced overexpression of miR-6216 inhibited NSC proliferation, and overexpression of RAB6B promoted NSC proliferation. These findings suggest that miR-6216 played an important role in regulating NSC proliferation via targeting RAB6B, and improve the understanding of the miRNA-mRNA regulatory network that affects NSC proliferation.

Celecoxib Reverse Invasion and Metastasis of Gastric Cancer through Lnc_AC006548.28-miR-223-LAMC2 Pathway.

Celecoxib, a specific cyclooxygenase-2 (COX-2) inhibitor, is a traditional nonsteroidal antipyretic analgesic and anti-inflammatory drug commonly used in clinic, which has inhibitory effect on colorectal cancer, gastric cancer, and other malignant tumors. This study showed that Celecoxib could significantly reverse the invasion and metastasis of gastric cancer and improved the pathological changes due to GC. We collected the clinical specimens to analyze the correlation between the expression of Lnc_AC006548.28, miR-223, and LAMC2. In the mouse model, Celecoxib can slowdown the growth of GC tumor and the occurrence of this effect may depend on Lnc_AC006548.28-miR-223-LAMC2 pathway, in vitro transfection, RT-PCR, western blot, CCK8, small chamber assay, flow cytometry, and immunohistochemistry to retest the protective effect of celecoxib. Our results showed that Celecoxib could reverse invasion and metastasis of gastric cancer through Lnc_AC006548.28-miR-223-LAMC2 pathway.

Exosome-mediated lncRNA SND1-IT1 from gastric cancer cells enhances malignant transformation of gastric mucosa cells via up-regulating SNAIL1.

BACKGROUND: Gastric cancer (GC), as one of the most common malignancies across the globe, is the fourth leading cause of cancer-related deaths. Though a large body of research has been conducted to develop the therapeutic methods of GC, the survival rate of advanced patients is still poor. We aimed to dig into the potential regulatory mechanism of GC progression. METHODS: Bioinformatics tools and fundamental assays were performed at first to confirm the candidate genes in our study. The functional assays and mechanism experiments were conducted to verify the regulatory mechanisms of the genes underlying GC progression. RESULTS: Long non-coding RNA (lncRNA) SND1 intronic transcript 1 (SND1-IT1) is highly expressed in exosomes secreted by GC cells. SND1-IT1 was verified to bind to microRNA-1245b-5p (miR-1245b-5p) through competitive adsorption to promote ubiquitin specific protease 3 (USP3) messenger RNA (mRNA) expression. SND1-IT1 was validated to recruit DEAD-box helicase 54 (DDX54) to promote USP3 mRNA stability. SND1-IT1 induces malignant transformation of GES-1 cells through USP3. USP3 mediates the deubiquitination of snail family transcriptional repressor 1 (SNAIL1). CONCLUSIONS: Exosome-mediated lncRNA SND1-IT1 from GC cells enhances malignant transformation of GES-1 cells via up-regulating SNAIL1.

MiR-130a-3p regulates neural stem cell differentiation in vitro by targeting Acsl4.

In the adult mammalian brain, neural stem cells (NSCs) are the precursor cells of neurons that contribute to nervous system development, regeneration, and repair. MicroRNAs (miRNAs) are small non-coding RNAs that regulate cell fate determination and differentiation by negatively regulating gene expression. Here, we identified a post-transcriptional mechanism, centred around miR-130a-3p that regulated NSC differentiation. Importantly, overexpressing miR-130a-3p promoted NSC differentiation into neurons, whereas inhibiting miR-130a-3p function reduced the number of neurons. Then, the quantitative PCR, Western blot and dual-luciferase reporter assays showed that miR-130a-3p negatively regulated acyl-CoA synthetase long-chain family member 4 (Acsl4) expression. Additionally, inhibition of Acsl4 promoted NSC differentiation into neurons, whereas silencing miR-130a-3p partially suppressed the neuronal differentiation induced by inhibiting Acsl4. Furthermore, overexpressing miR-130a-3p or inhibiting Acsl4 increased the levels of p-AKT, p-GSK-3ß and PI3K. In conclusion, our results suggested that miR-130a-3p targeted Acsl4 to promote neuronal differentiation of NSCs via regulating the Akt/PI3K pathway. These findings may help to develop strategies for stem cell-mediated treatment for central nervous system diseases.

circRNA Acbd6 promotes neural stem cell differentiation into cholinergic neurons via the miR-320-5p-Osbpl2 axis.

Neural stem cells (NSCs) persist in the dentate gyrus of the hippocampus into adulthood and are essential for both neurogenesis and neural circuit integration. Exosomes have also been shown to play vital roles in regulating biological processes of receptor cells as a medium for cell-to-cell communication signaling molecules. The precise molecular mechanisms of exosome-mediated signaling, however, remain largely unknown. Here, we found that exosomes produced by denervated hippocampi following fimbria-fornix transection could promote the differentiation of hippocampal neural precursor cells into cholinergic neurons in coculture with NSCs. Furthermore, we found that 14 circular RNAs (circRNAs) were upregulated in hippocampal exosomes after fimbria-fornix transection using high-throughput RNA-Seq technology. We further characterized the function and mechanism by which the upregulated circRNA Acbd6 (acyl-CoA-binding domain-containing 6) promoted the differentiation of NSCs into cholinergic neurons using RT-quantitative PCR, Western blot, ELISA, flow cytometry, immunohistochemistry, and immunofluorescence assay. By luciferase reporter assay, we demonstrated that circAcbd6 functioned as an endogenous miR-320-5p sponge to inhibit miR-320-5p activity, resulting in increased oxysterol-binding protein-related protein 2 expression with subsequent facilitation of NSC differentiation. Taken together, our results suggest that circAcbd6 promotes differentiation of NSCs into cholinergic neurons via miR-320-5p/oxysterol-binding protein-related protein 2 axis, which contribute important insights to our understanding of how circRNAs regulate neurogenesis.

SSRP1 affects the growth and apoptosis of gastric cancer cells through AKT pathway.

Background: We aimed to determine the SSRP1's potential influence on the apoptosis and proliferation of gastric cancer (GC) cells and its regulatory mechanism. Methods: SSRP1 expression in GC cells and tissues was detected via quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The interrelation between clinicopathological characteristics of GC patients and SSRP1 expression was analysed via x2 test, and the correlation between SSRP1 expression and overall survival rate was analysed using Kaplan-Meier survival analysis. After the knockdown of SSRP1 in AGS cells, the SSRP1 expression, colony formation ability, cell viability, cell cycle changes, apoptosis rate, and migration and invasion ability were detected through qRT-PCR, colony formation assay, CCK8 assay, flow cytometry and transwell test, respectively. Finally, the effects of down-regulation of SSRP1 on the expressions of phosphorylated-protein kinase B (p-AKT), B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax) were explored using Western blotting. Results: SSRP1 displayed a high expression in GC cells and tissues. SSRP1 expression was closely interrelated to the TNM stage, lymph node metastasis and tumour size. The survival rate of patients was markedly shorter in the high expression group than in the lower expression group. After the knockdown of SSRP1 in cells, the viability and colony formation ability of AGS cells were inhibited. In addition, the cell ratio in the G1 phase was increased, while that in the S phase declined, and the cell invasion and migration were obviously weakened. It was found from Western blotting that the knockdown of SSRP1 could evidently suppress the protein levels of Bcl-2 and p-AKT but promote the protein expression of Bax, indicating that silencing SSRP1 can inhibit the proliferative capacity and increase the number of GC cells through inactivating the AKT signalling pathway. Conclusions: SSRP1 rose up in GC tissues and cells. Reduction of SSRP1 can inhibit the proliferative capacity and increase the number of GC cells through inactivating the AKT signalling pathway.

Anti-apoptotic effects of diosgenin on ovariectomized hearts.

BACKGROUND: The anti-apoptotic effects of diosgenin, a steroid saponin, on hearts in female with estrogen deficiency have been less studied. This study aimed to evaluate the anti-apoptotic effects of diosgenin on cardiac widely dispersed apoptosis in a bilateral ovariectomized animal model. METHODS: A total of 60 female Wistar rats, aged 6-7 months, were divided into the sham-operated group (Sham), bilateral ovariectomized rats for 2 months, and ovariectomized rats administered with 0, 10, 50, or 100 mg/kg diosgenin daily (OVX, OVX 10, OVX 50, and OVX 100, respectively) in the second month. The excised hearts were analyzed by H&E staining, TUNEL(+) assays and Western Blot. RESULT: Cardiac TUNEL(+) apoptotic cells, the levels of Fas ligand, Fas death receptors, Fas-associated death domain, active caspase-8, and active caspase-3 (FasL/Fas-mediated pathways) as well as the levels of Bax, Bad, Bax/Bcl2, Bad/p-Bad, cytosolic Cytochrome c, active caspase-9, and active caspase-3 (mitochondria-initiated pathway) were increased in OVX compared with Sham group but those were decreased in OVX 50 compared with OVX. CONCLUSION: Diosgenin appeared to prevent or suppress ovariectomy-induced cardiac FasL/Fas-mediated and mitochondria-initiated apoptosis. These findings might provide one of the possible therapeutic approaches of diosgenin for potentially preventing cardiac apoptosis in women after bilateral ovariectomy or women with estrogen deficiency.

miR-103-3p targets Ndel1 to regulate neural stem cell proliferation and differentiation.

The regulation of adult neural stem cells (NSCs) is critical for lifelong neurogenesis. MicroRNAs (miRNAs) are a type of small, endogenous RNAs that regulate gene expression post-transcriptionally and influence signaling networks responsible for several cellular processes. In this study, miR-103-3p was transfected into neural stem cells derived from embryonic hippocampal neural stem cells. The results showed that miR-103-3p suppressed neural stem cell proliferation and differentiation, and promoted apoptosis. In addition, miR-103-3p negatively regulated NudE neurodevelopment protein 1-like 1 (Ndel1) expression by binding to the 3' untranslated region of Ndel1. Transduction of neural stem cells with a lentiviral vector overexpressing Ndel1 significantly increased cell proliferation and differentiation, decreased neural stem cell apoptosis, and decreased protein expression levels of Wnt3a, ß-catenin, phosphor-GSK-3ß, LEF1, c-myc, c-Jun, and cyclin D1, all members of the Wnt/ß-catenin signaling pathway. These findings suggest that Ndel1 is a novel miR-103-3p target and that miR-103-3p acts by suppressing neural stem cell proliferation and promoting apoptosis and differentiation. This study was approved by the Animal Ethics Committee of Nantong University, China (approval No. 20200826-003) on August 26, 2020.

MiR-674-5p Suppresses the Proliferation and Migration of Glioma Cells by Targeting Cul4b.

Glioma multiforme (GBM) is the most common malignant primary brain tumors. Despite the considerable advances in GBM treatment, it is still one of the most lethal forms of brain tumor. New clinical biomarkers and therapeutic targets are immediately required. MicroRNAs (miRNAs) are a class of small, evolutionarily conserved noncoding RNAs and have emerged as the key regulators of many cancers. Here in this study, we showed that miR-674-5p was probably an important regulator of glioma cell growth. After the transfection with miR-674-5p mimic or inhibitor, we found that the expression level of miR-674-5p was negatively related with cell proliferation and migration in C6 cells. Based on the prediction of the target genes of miR-674-5p on the website, we chose Cullin 4B (Cul4b), a gene upregulated in GBM, and proved that it was a target of miR-674-5p. In addition, we explored the role of miR-674-5p in glioma growth in vivo. Taken together, the present study indicated that miR-674-5p suppressed glioma cell proliferation and migration by targeting Cul4b.

P4HA2 promotes cell proliferation and migration in glioblastoma.

Glioblastoma (GBM) is a primary malignant tumor characterized by high infiltration and angiogenesis in the brain parenchyma. Glioma stem cells (GSCs), a heterogeneous GBM cell type with the potential for self-renewal and differentiation to tumor cells, are responsible for the high malignancy of GBM. The purpose of the present study was to investigate the roles of significantly differentially expressed genes between GSCs and GBM cells in GBM progression. The gene profiles GSE74304 and GSE124145, containing 10 GSC samples and 12 GBM samples in total, were obtained from the Gene Expression Omnibus (GEO) database. The overlapping differentially expressed genes were identified with GEO2R tools and Venn software online. Subsequently, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed on the 41 upregulated and 142 downregulated differentially expressed genes in GSCs compared with in GBM cells via the DAVID website. Protein-protein interaction and module analyses in Cytoscape with the STRING database revealed 21 hub genes that were downregulated in GSCs compared with in GBM cells. Survival analysis conducted via the GEPIA2 website revealed that low expression levels of the hub genes prolyl 4-hydroxylase subunit α2 (P4HA2), TGF-ß induced, integrin subunit α3 and thrombospondin 1 were associated with significantly prolonged survival time in patients with GBM. Further experiments were performed focusing on P4HA2. Reverse transcription-quantitative PCR was used to detect P4HA2 gene expression. In agreement with the bioinformatics analysis, P4HA2 expression was higher in U87 cells than in GSCs. Cell Counting Kit-8, EdU incorporation, cell cycle analysis, wound healing and Transwell assays demonstrated that the cell proliferation and migration increased after P4HA2 overexpression and decreased after P4HA2-knockdown. In conclusion, the present study demonstrated that low P4HA2 expression in GSCs promoted GBM cell proliferation and migration, suggesting that P4HA2 may act as a switch in the transition from GSCs to GBM cells.

CircHECTD1 Regulates Cell Proliferation and Migration by the miR-320-5p/SLC2A1 Axis in Glioblastoma Multiform.

Glioblastoma multiform (GBM) is the most common and malignant primary brain cancer in adults, and thus, novel potential therapeutic targets for diagnosis and treatment are urgently needed. Circular RNAs (circRNAs) are a class of widespread and diverse endogenous RNAs that have been suggested as potential critical mediators during progression of various tumors. In this study, we investigated the involvement of circHECTD1 in GBM progression. CircHECTD1 Lentivirus, miR-320-5p mimic, and SLC2A1 Lentivirus were transduced into cancer cells independently or together. circHECTD1, miR-320-5p, and SLC2A1 level were detected by qRT-PCR. Western blot and qRT-PCR were applied to measure the expression of SLC2A1, CyclinD1, CDK2, and PCNA. Flow cytometry, EdU, colony formation, Transwell and wound-healing assays were conducted to assess cell proliferation and migration. Luciferase reporter assays were performed to determine the effect of miR-320-5p on circHECTD1 or SLC2A1. Xenograft experiments were implemented to evaluate tumor growth in vivo. CircHECTD1 expression led to the promotion of proliferation and migration of GBM cells. In addition, circHECTD1 acted as a ceRNA to interact with miR-320-5p, which targeted the solute carrier family 2 member 1 (SLC2A1). In vivo experiments also revealed that circHECTD1 promoted tumor growth. Collectively, our findings showed that the circHECTD1-miR-320-5p-SLC2A1 regulatory pathway promoted the progression of GBM, suggesting that circHECTD1 may be a therapeutic target for GBM.

miR-33-3p Regulates PC12 Cell Proliferation and Differentiation In Vitro by Targeting Slc29a1.

MicroRNA-33-3p (miR-33-3p) has been widely investigated for its roles in lipid metabolism and mitochondrial function; however, there are few studies on miR-33-3p in the context of neurological diseases. In this study, we investigated the functional role of miR-33-3p in rat pheochromocytoma PC12 cells. A miR-33-3p mimic was transduced into PC12 cells, and its effects on proliferation, apoptosis, and differentiation were studied using the MTS assay, EdU labeling, flow cytometry, qRT-PCR, western blot, ELISA, and immunofluorescence. We found that miR-33-3p significantly suppressed PC12 cell proliferation, but had no effect on apoptosis. Furthermore, miR-33-3p promoted the differentiation of PC12 cells into Tuj1-positive and choline acetyltransferase-positive neuron-like cells. Mechanistically, miR-33-3p repressed the expression of Slc29a1 in PC12 cells. Importantly, knocking down Slc29a1 in PC12 cells inhibited proliferation and induced differentiation into neuron-like cells. In conclusion, this study showed that miR-33-3p regulated Slc29a1, which in turn controlled the proliferation and differentiation of PC12 cells. Thus, we hypothesize that the miR-33-3p/Slc29a1 axis could be a promising therapeutic target for recovering neurons and the cholinergic nervous system.

Research progress of the transcription factor Brn4 (Review).

Brain 4 (Brn4) is a transcription factor belonging to the POU3 family, and it is important for the embryonic development of the neural tube, inner ear and pancreas. In addition, it serves a crucial role in neural stem cell differentiation and reprogramming. The present review aimed to summarize the chromosomal location, species homology, protein molecular structure and tissue distribution of Brn4, in addition to its biological processes, with the aim of providing a reference of its structure and function for further studies, and its potential use as a gene therapy target.

Expression and function of Ndel1 during the differentiation of neural stem cells induced by hippocampal exosomesticle.

BACKGROUND: In the brain of adult mammals, neural stem cells persist in the subventricular zone of the lateral ventricle and the subgranular zone of the dentate gyrus, which are specialized niches with proliferative capacity. Most neural stem cells are in a quiescent state, but in response to extrinsic stimuli, they can exit from quiescence and become reactivated to produce new neurons, so neural stem cells are considered to be a potential source for cell replacement therapy of many nervous system diseases. We characterized the expression of Ndel1 during the differentiation of neural stem cells induced by hippocampus exosomes, and assessed the effect of Ndel1 on neural stem cells differentiation. METHODS: Hippocampal exosomes were isolated and extracted, and co-cultured exosomes with neural stem cells. Western blot, flow cytometry, and immunofluorescence analyses were used to analyze expression of neuronal markers. Further, utilizing high-throughput RNA sequencing technology, we found that nudE neurodevelopment protein 1-like 1 was significantly upregulated in exosomes derived from denervated hippocampus, and then characterized its mechanism and function during neural stem cells differentiation by qRT-PCR, western blot, flow cytometry, and immunofluorescence analyses. RESULTS: Our results revealed that exosomes of denervated hippocampus promoted the differentiation of neural stem cells into neuron. Hence, we identified that nudE neurodevelopment protein 1-like 1 was significantly upregulated and highly expressed in the nervous system. In addition, we found that miR-107-3p may regulate neural stem cell differentiation by targeting Ndel1. CONCLUSIONS: Our results revealed that deafferentation of the hippocampal exosomes co-cultured with neural stem cells could promote them to differentiate into neurons. Hence, we found that miR-107-3p may regulate neural stem cells differentiation by targeting Ndel1. Importantly, Ndel1 enhanced spatial learning and hippocampal neurogenesis in rats after fimbria fornix transection in vivo. These findings set the stage for a better understanding of neurogenesis, a process that 1 day may inspire new treatments for central nervous system diseases.

The role of hippocampal niche exosomes in rat hippocampal neurogenesis after fimbria-fornix transection.

Exosomes transfer signaling molecules such as proteins, lipids, and RNAs to facilitate cell-cell communication and play an important role in the stem cell microenvironment. In previous work, we demonstrated that rat fimbria-fornix transection (FFT) enhances neurogenesis from neural stem cells (NSCs) in the subgranular zone (SGZ). However, how neurogenesis is modulated after denervation remains unknown. Here, we investigated whether exosomes in a denervated hippocampal niche may affect neurogenesis. Using the FFT rat model, we extracted hippocampal exosomes and identified them using western blots, transmission electron microscopy (TEM), and nanoparticle size measurement. We also used RNA sequencing and bioinformatic analysis of exosomes to identify noncoding RNA expression profiles and neurogenesis-related miRNAs, respectively. RNA sequencing analysis demonstrated 9 upregulated and 15 downregulated miRNAs. miR-3559-3P and miR-6324 increased gradually after FFT. Thus, we investigated the function of miR-3559-3P and miR-6324 with NSC proliferation and differentiation assays. Transfection of miR-3559-3p and miR-6324 mimics inhibited the proliferation of NSCs and promoted the differentiation of NSCs into neurons, while miR-3559-3p and miR-6324 inhibitors promoted NSC proliferation and inhibited neuronal differentiation. Additionally, the exosome marker molecules CD9, CD63, and Alix were expressed in exosomes extracted from the hippocampal niche. Finally, TEM showed that exosomes were ∼100 nm in diameter and had a "saucer-like" bilayer membrane structure. Taken together, these findings suggest that differentially expressed exosomes and their related miRNAs in the denervated hippocampal niche can promote differentiation of NSCs into neurons.

GAS5 which is regulated by Lhx8 promotes the recovery of learning and memory in rats with cholinergic nerve injury.

Damage to the cholinergic system in central nervous system injuries such as traumatic brain injury (TBI) and neurodegenerative diseases leads to impaired learning and cognition. Neural stem cells (NSCs) have self-renewal capacity and multi-directional differentiation potential and considered the best source of cells for cell replacement therapy. However, how to promote the differentiation of NSCs into neurons is a major challenge in current research. Lhx8 has a specific effect on the development of the cholinergic nervous system, but its exact function is unclear. In this study, we found that Lhx8 could regulate the expression of Growth arrest-specific (GAS)5 which has been implicated in cancer but was less studied in the nervous system. Additionally, results from PCR, fluorescence in situ hybridization, and immunocytochemical analyses showed that GAS5 is mainly expressed in the cytoplasm of hippocampal neural stems cells and promotes their differentiation into neurons; the Morris water maze test demonstrated that GAS5 overexpression restored learning and memory in rats with cholinergic injury. These findings indicate that GAS5, which is regulated by Lhx8, improve brain function following cholinergic nerve injury.

Long non­coding RNA HOXA11­AS accelerates cell proliferation and epithelial­mesenchymal transition in hepatocellular carcinoma by modulating the miR­506­3p/Slug axis.

Hepatocellular carcinoma (HCC) is an aggressively malignant type of cancer with a complex pathogenesis. Multiple studies have identified that lncRNA HOXA11­AS is involved in the development of HCC. Nevertheless, the pathological mechanisms of HOXA11­AS in the development of HCC require further investigation. In the present study, the role and underlying mechanisms of HOXA11­AS in HCC were examined. RT­qPCR revealed that HOXA11­AS expression was increased, while that of miR­506­3p was decreased in HCC tissues and cells compared with that in adjacent non­tumor tissues and normal hepatic cells. Dual­luciferase reporter assay and RNA pull­down assay indicated that HOXA11­AS directly interacted with miR­506­3p. miR­506­3p downregulation reversed the inhibitory effects of HOXA11­AS deletion on cell proliferation, invasion and epithelial­mesenchymal transition (EMT), as shown by CCK­8 and Transwell assays, as well as western blot analysis. Bioinformatics analysis and dual­luciferase reporter assay indicated that Slug was a target gene of miR­506­3p. The overexpression of Slug reversed the effects of HOXA11­AS deletion on the viability, invasion and the EMT of HCC cells. Taken together, the present study demonstrates that HOXA11­AS functions as an oncogene to promote the progression of HCC via the miR­506­3p/Slug axis, providing a therapeutic target for patients with HCC.