MiR-4763-3p targeting <i>RASD2</i>as a Potential Biomarker and Therapeutic Target for Schizophrenia

Wang, Jiao; Qi, Wenxin; Shi, Hongwei; Huang, Lin; Ning, Fujiang; Wang, Fushuai; Wang, Kai; Bai, Haotian; Wu, Hao; Zhuang, Junyi; Hong, Huanle; Zhou, Haicong; Hu, Feng; Zhou, Yinping; Dong, Naijun; Liu, Li; Kong, Yanyan; Xie, Jing; Zhao, Rongbao

doi:10.14336/ad.2022.0103

Cited by 4 publications

(4 citation statements)

References 46 publications

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“…Immunoblotting analysis was performed as described previously [ 26 ]. In detail, wash the cells with pre-cooled PBS and lyse them on ice with Western and IP lysate (Beyotime, China) for 15 min.…”

Section: Methodsmentioning

confidence: 99%

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Dong,

Qi,

et al. 2024

J Exp Clin Cancer Res

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Background LncRNAs regulate tumorigenesis and development in a variety of cancers. We substantiate for the first time that LINC00606 is considerably expressed in glioblastoma (GBM) patient specimens and is linked with adverse prognosis. This suggests that LINC00606 may have the potential to regulate glioma genesis and progression, and that the biological functions and molecular mechanisms of LINC00606 in GBM remain largely unknown. Methods The expression of LINC00606 and ATP11B in glioma and normal brain tissues was evaluated by qPCR, and the biological functions of the LINC00606/miR-486-3p/TCF12/ATP11B axis in GBM were verified through a series of in vitro and in vivo experiments. The molecular mechanism of LINC00606 was elucidated by immunoblotting, FISH, RNA pulldown, CHIP-qPCR, and a dual-luciferase reporter assay. Results We demonstrated that LINC00606 promotes glioma cell proliferation, clonal expansion and migration, while reducing apoptosis levels. Mechanistically, on the one hand, LINC00606 can sponge miR-486-3p; the target gene TCF12 of miR-486-3p affects the transcriptional initiation of LINC00606, PTEN and KLLN. On the other hand, it can also regulate the PI3K/AKT signaling pathway to mediate glioma cell proliferation, migration and apoptosis by binding to ATP11B protein. Conclusions Overall, the LINC00606/miR-486-3p/TCF12/ATP11B axis is involved in the regulation of GBM progression and plays a role in tumor regulation at transcriptional and post-transcriptional levels primarily through LINC00606 sponging miR-486-3p and targeted binding to ATP11B. Therefore, our research on the regulatory network LINC00606 could be a novel therapeutic strategy for the treatment of GBM. Graphical Abstract LINC00606 is highly expressed in GBM patients with carcinogenic function and correlated with poor prognosis. LINC00606 regulates glioblastoma progression by sponging miR-486-3p and interacting with ATP11B.

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Section: Methodsmentioning

confidence: 99%

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Dong,

Qi,

et al. 2024

J Exp Clin Cancer Res

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“…In this study, we screened and found that miR-4763-3p is dysregulated in the early stages of AD and is positively correlated with age. Previous research [20] has shown that miR-4763-3p is closely related to cognition. Therefore, we further explored its ameliorative effect on cognitive decline in early-stage AD.…”

Section: Introductionmentioning

confidence: 92%

“…According to the study, only hsa-miR- 4763-3p, hsa-miR-342-3p, hsa-miR-361-3p, hsa-miR-485-3p and hsa-miR-211-5p are thought to be cognitively relevant [20,[23][24][25][26]. We examined miRNA expression in the hippocampal tissues of AD-MCI and WT mice at 6 and 12 months.…”

Section: Mir-4763-3p Antagomir Ameliorates Cognitive Decline In Ad-mc...mentioning

confidence: 99%

Inhibition of miR-4763-3p expression in the brains of AD-MCI mice activates the PI3K/mTOR/Bcl2 autophagy signaling pathway to reverse neuronal loss and ameliorate cognitive decline

Qi,

Dong,

et al. 2024

Preprint

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Background Cognitive decline and memory impairment are frequently observed in Alzheimer's disease (AD) patients and are closely associated with dysfunctional autophagy and neuroinflammation, which subsequently result in neuronal apoptosis and synaptic damage. Aberrant regulation of microRNAs (miRNAs) has been implicated in the pathogenesis of AD and may play a pivotal role in the early stages of the disease. Objectives To examine the role of a miR-4763-3p antagomir in ameliorating cognitive decline in mild cognitive impairment (MCI)-AD mice and to elucidate the underlying mechanisms involved. Methods Fluorescence in situ hybridization was used to demonstrate that miR-4763-3p is highly expressed in postmortem hippocampal tissue from AD patients and colocalizes with the Aβ and Tau proteins. Stereotactic injection of the miR-4763-3p antagomir and subsequent behavioral experiments revealed its ability to ameliorate cognitive decline in AD-MCI mice. RNA-seq, tissue staining, and SH-SY5Y cell experiments were used to explore specific molecular mechanisms and associated signaling pathways. Results The miR-4763-3p antagomir targeted ATP11A to enhance inward flipping of the "eat me" phosphatidylserine signal on the surface of neuronal cells, effectively alleviating brain inflammation and neuronal loss and improving synaptic morphology in AD-MCI mice. Furthermore, the miR-4763-3p antagomir increased autophagy in the early-stage AD-MCI brain, promoted the clearance of Aβ proteins, and reduced the deposition of lipofuscin. These findings confirm that miR-4763-3p targets ATP11A to regulate the PI3K/AKT/mTOR/Bcl2 signaling pathway, thereby promoting neuronal autophagy and reducing apoptotic crosstalk. Conclusions The miR-4763-3p antagomir has the potential to reverse neuronal apoptosis and enhance autophagy levels, improving the inflammatory microenvironment in brain tissue and thus improving learning and memory in early-stage AD-MCI mice to mitigate cognitive decline. Our data offer a promising strategy for the treatment of AD-MCI patients.

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“…focused on the abnormally expressed miR-4763-3p through biological information, and the expression change was also confirmed in patients with schizophrenia (Wang et al ., 2022). Moreover, miR-4763-3p inhibition can alleviate the symptoms of schizophrenia by targeting RASD2 in schizophrenia model mice (Wang et al ., 2022). Recently, Davarinejad et al .…”

Section: Introductionmentioning

confidence: 94%

Diagnostic significance and potential function of miR-320d in schizophrenia

Ren,

Si,

Sui

2024

Psychiatric Genetics

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Schizophrenia is a chronic brain disorder and needs objective diagnostic biomarkers. MicroRNAs are highly expressed in the nervous system. The study investigated the expression and clinical values of serum miR-320d in schizophrenia patients. In addition, the underlying mechanism was preliminarily examined via bioinformatic analysis. Serum samples were collected from 57 patients with first-episode schizophrenia and 62 healthy controls. The cognitive function of patients was assessed via Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) consisting of seven domains. Serum miR-320d levels were tested via qRT-PCR. The miRNA target predictions were obtained from Target Scan, and annotated through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Based on the GSE167630 dataset, downregulated serum miR-320d in schizophrenia was identified, which was determined in the serum of schizophrenia patients. Serum miR-320d presented a conspicuous relationship with MCCB score in both the control group and the schizophrenia group. After adjusting for age, sex, BMI, and education, serum miR-320d was still independently related to the occurrence of schizophrenia. It can identify schizophrenia cases from healthy ones with an AUC of 0.931. The Go enrichment analysis indicated that the target genes were mainly enriched in homophilic cell adhesion and cell-cell adhesion via plasma-membrane adhesion molecules, and GTPase activity and guanosine diphosphate (GDP) binding. Rap1 signaling pathway was enriched via KEGG analysis. Serum miR-320d can be taken as a candidate marker for the diagnosis of schizophrenia. Its regulatory role in neuronal cell adhesion and Rap1 signaling pathway might be the potential underlying mechanism of miR-320d in schizophrenia.

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MiR-4763-3p targeting RASD2as a Potential Biomarker and Therapeutic Target for Schizophrenia

Cited by 4 publications

References 46 publications

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

LINC00606 promotes glioblastoma progression through sponge miR-486-3p and interaction with ATP11B

Inhibition of miR-4763-3p expression in the brains of AD-MCI mice activates the PI3K/mTOR/Bcl2 autophagy signaling pathway to reverse neuronal loss and ameliorate cognitive decline

Diagnostic significance and potential function of miR-320d in schizophrenia

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