Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Li, Bao-Guang; Wu, Wenjuan; Zheng, Huacheng; Yang, Hongbo; Zuo, Yue-Xian; Cui, Xiao-Pu

doi:10.1002/kjm2.12102

Cited by 24 publications

(13 citation statements)

References 37 publications

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“…For instance, GAS5 was upregulated in atherosclerosis, suggesting that GAS5 implicated in the development of atherosclerosis [22]. Moreover, the expression levels of GAS5 remarkably increased in epilepsy and ischemic heart disease [23,24]. Additionally, in this study, we found that GAS5 expression signi cantly downregulated in osteosarcoma, which was also consistent with some reports.…”

Section: Discussionsupporting

confidence: 92%

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

Liu¹,

Chen²,

Ma³

et al. 2020

Preprint

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Background: Accumulating evidence has shown that lncRNA growth arrest special 5 (GAS5) is a well‑known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is largely unclear. Here, we explore the role of GAS5 in progression of osteosarcoma. Methods: The expression level of GAS5 was detected in human osteosarcoma tissues and matched adjacent tissues, as well as osteosarcoma cell lines and non-malignant osteoblast cells. Then, in vitro gain- and loss-of-function experiments, with the pcDNA-GAS5 expression vector and GAS5-siRNA, were performed in U2OS and HOS cells to determine the effect of GAS5 on osteosarcoma cell proliferation and invasion. Subsequently, we searched potential miRNA targets with bioinformatics analysis and confirmed their interaction by using luciferase reporter gene and RNA pull-down assays. The function and mechanism of miR-23a-3p in proliferation and invasion was also investigated in U2OS and HOS cells. Furthermore, rescue experiments were performed to verify the involvement of miR-23a-3p and its target gene in GAS5-mediated cell behaviors. Finally, a xenograft nude mouse model was established by subcutaneous injection with U2OS cells overexpressing GAS5 or not, and the effect of GAS5 on tumor growth in vivo was evaluated. Results: GAS5 was downregulated in human osteosarcoma tissues and cell lines. Overexpression of GAS5 could significantly suppress, and downregulation of GAS5 promoted, proliferation and invasion of osteosarcoma cells. GAS5 could directly bind with and downregulated miR-23a-3p that post-transcriptionally downregulated the tumor suppressor PTEN and positively regulated proliferation and invasion of osteosarcoma cells. Rescue experiments confirmed the involvement of miR-23a-3p and PTEN in GAS5-mediated cell behaviors by modifying the phosphatidylinositol-3-kinases/protein-serine-threonine kinase (PI3K/AKT) pathway. GAS5 could inhibit tumor growth in vivo . Conclusion: GAS5 functions as a competing endogenous RNA , sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.

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Section: Discussionsupporting

confidence: 92%

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

Liu¹,

Chen²,

Ma³

et al. 2020

Preprint

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“…was a co-occurrence and characteristic phenotype in different epilepsy models, which suggested that miR-135a-5p might serve as a potential biomarker of epilepsy. In addition, previous studies demonstrated that miR-135a-5p inhibition effectively alleviated epilepsy-induced nerve injury (20,33). In the present study, the number of BV2 cells was significantly increased and the rate of apoptosis was notably decreased by miR-135a-5p inhibitor transfection, which suggested that miR-135a-5p might serve as a potential therapeutic target for epilepsy.…”

Section: Discussionsupporting

confidence: 71%

“…Moreover, SIRT1 inhibition attenuated, but did not completely block the effects mediated by miR-135a-5p inhibitor. There are a number of potential explanations for the aforementioned findings: i) There was a high level of SIRT1 protein expression following siRNA transfection, and the residual SIRT1 protein might be sufficient to regulate cell survival; ii) miR-135a-5p might serve roles via other target proteins, for example, it has been reported that potassium voltage-gated channel subfamily Q member 3, caspase activity and apoptosis inhibitor 1 (CAAP1) and other proteins are regulated by miR-135a-5p, and participate in cell proliferation and apoptosis (20,33); and iii) as aforementioned, SIRT1 protein expression levels and activity levels were dynamically altered post-seizure, thus inhibiting SIRT1 protein expression might trigger other cellular mechanisms, resulting in a compensatory effect.…”

Section: Discussionmentioning

confidence: 99%

miR‑135a‑5p inhibitor protects glial cells against apoptosis via targeting SIRT1 in epilepsy

et al. 2021

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Epilepsy is a common neurological disease that can induce severe physiological brain damage, including nerve cell apoptosis. MicroRNAs (miRs) have been widely investigated in epilepsy therapy. miR-135a-5p expression levels in children with temporal lobe epilepsy were found to be significantly increased. However, whether miR-135a-5p participates in epilepsy-induced cell apoptosis is not completely understood. In the present study, an in vitro model of epilepsy in BV2 microglia cells was induced using 6-µm kainic acid (KA). Reverse-transcription quantitative PCR was performed to analyze miR-135a-5p and sirtuin 1 (SIRT1) mRNA expression levels. Western blotting was performed to measure SIRT1 protein expression levels. BV2 cell proliferation and apoptosis were assessed by performing MTT assays and flow cytometry, respectively. A BCA protein assay kit was used to detect caspase-3 and caspase-9 activities. TargetScan and dual luciferase reporter assays were performed to investigate the interaction between miR-135a-5p and the 3'-untranslated region (UTR) of SIRT1. miR-135a-5p expression was significantly increased in the KA-induced in vitro model of epilepsy in BV2 microglia. miR-135a-5p inhibitor effectively promoted BV2 microglia proliferation and inhibited microglia apoptosis, whereas small interfering RNA targeting SIRT1 significantly repressed BV2 microglia proliferation and induced microglia apoptosis. In addition, the results demonstrated that the 3'-UTR of SIRT1 mRNA was targeted by miR-135a-5p, and SIRT1 knockdown attenuated miR-135a-5p inhibitor-mediated effects on epilepsy. In summary, the results of the present study identified the role of miR-135a-5p inhibitor pretreatment in protecting nerve cells against epilepsy-induced apoptosis and provided a novel strategy for the treatment of neural damage in seizures.

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“…As one of the most prevailing neurological syndromes, epilepsy influences over 50 million individuals globally [1]. The principal feature linked with epilepsy is intense and frequent aberrant emission of brain neurons, clinically manifested with dysfunction of transient central nervous system (CNS) [2].…”

Section: Introductionmentioning

confidence: 99%

“…Contemporary studies have determined that specific lncRNAs are closely linked with epilepsy. For instance, evidence provided by Li et al emphasizes that lncRNA GAS5 silencing obstructed the onset and progression of epilepsy [2].…”

Section: Introductionmentioning

confidence: 99%

Long non-coding RNA NEAT1 aggravates epilepsy and seizure-induced neuronal damage by regulating microRNA-139/ROCK1 axis

Hao

Tao

et al. 2020

Preprint

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Background Both long non-coding RNA (lncRNA) NEAT1 and microRNA (miR)-139 are crucial gene regulators in various disorders. This study aims to investigate their role in epilepsy and seizure-induced neuronal damage. Methods In this research, rat model of epilepsy was established by pilocarpine induction. The RNA and protein expression in hippocampal tissues and neurons were determined by RT-qPCR and Western blot analysis, respectively. Microarray analysis was used to predict the relationship between NEAT1 and miR-139 or between miR-139 and ROCK1, and dual luciferase reporter gene assay was performed to verify the interaction. The endogenous expression of related genes was modulated by recombinant plasmids and cell transfection. The cell apoptosis, levels of inflammatory factors and cell proliferation were detected by flow cytometry, ELISA and EdU assay. Results LncRNA NEAT1 and ROCK1 was upregulated, while the miR-139 was downregulated in hippocampal tissues and neurons of epileptic rats. Overexpression of NEAT1 decreased the activity of neurons, increased cell apoptosis, and increased the level of inflammatory factors. NEAT1 negatively targeted miR-139 to upregulate ROCK1. The RhoA/ROCK1 signaling pathway was activated by NEAT1 overexpression and miR-139 downregulation. Conclusion LncRNA NEAT1 suppressed pilocarpine-induced epilepsy by inhibiting apoptosis of hippocampal neurons through miR-139/RhoA/ROCK1 axis, and thereby inhibiting neuronal injury induced by seizure.

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Long noncoding RNA GAS5 silencing inhibits the expression of KCNQ3 by sponging miR‐135a‐5p to prevent the progression of epilepsy

Cited by 24 publications

References 37 publications

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

miR‑135a‑5p inhibitor protects glial cells against apoptosis via targeting SIRT1 in epilepsy

Long non-coding RNA NEAT1 aggravates epilepsy and seizure-induced neuronal damage by regulating microRNA-139/ROCK1 axis

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