LncRNA-Meg3 promotes Nlrp3-mediated microglial inflammation by targeting miR-7a-5p

Meng, Jiao; Ding, Ting; Chen, Yuhua; Long, Tianlin; Xu, Quanhua; Lian, Wenqing; Liu, Wei

doi:10.1016/j.intimp.2020.107141

Cited by 52 publications

(33 citation statements)

References 45 publications

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“…ceRNAs have been reported to regulate pyroptosis regulators. For instance, HOX transcript antisense RNA/miR-455-3p regulated NLRP1-mediated inflammasome activation and X inactive specific transcript/miR-133-3p or maternally expressed 3/miR-7a-5p regulated NLRP3-mediated inflammasome activation ( 55 , 56 ). In the present study, pyroptosis execution protein GSDME was first identified as a target of miR-448 and secondly, it was identified that ceRNA NEAT1/miR-448 may regulate IR-induced GSDME-mediated pyroptosis and viability in human colorectal cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Su¹,

Duan²,

Zhu³

et al. 2021

Int J Oncol

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Pyroptosis is mediated by gasdermins and serves a critical role in ionizing radiation (IR)-induced damage in normal tissues, but its role in cancer radiotherapy and underlying mechanisms remains unclear. Long non-coding (lnc) RNAs serve important roles in regulating the radiosensitivity of cancer cells. The present study aimed to investigate the mechanistic involvement of lncRNAs in IR-induced pyroptosis in human colorectal cancer HCT116 cells. LncRNA, microRNA (miR)-448 and gasdermin E (GSDME) levels were evaluated using reverse transcription-quantitative polymerase chain reaction. Protein expression and activation of gasdermins were measured using western blotting. The binding association between miR-448 and GSDME was assessed using the dual-luciferase reporter assay. Pyroptosis was examined using phase-contrast microscopy, flow cytometry, Cell Counting Kit-8 assay and lactate dehydrogenase release assay. IR dose-dependently induced GSDME-mediated pyroptosis in HCT116 cells. GSDME was identified as a downstream target of miR-448. LncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) was upregulated in response to IR and enhanced GSDME expression by negatively regulating miR-448 expression. Notably, NEAT1 knockdown suppressed IR-induced pyroptosis, full-length GSDME expression and GSDME cleavage compared with that in irradiated cells. In addition, NEAT1 knockdown rescued the IR-induced decrease in cell viability in HCT116 cells. The findings of the present study indicated that lncRNA NEAT1 modulates IR-induced pyroptosis and viability in HCT116 cells via miR-448 by regulating the expression, but not activation of GSDME. The present study provides crucial mechanistic insight into the potential role of lncRNA NEAT1 in IR-induced pyroptosis.

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Section: Discussionmentioning

confidence: 99%

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Su¹,

Duan²,

Zhu³

et al. 2021

Int J Oncol

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“…Also, lncRNA MRAK009713 [ 9 ], KCNA2-AS [ 10 ], LncRNA H19 [ 11 ], etc., participate in the evolvement of NP. As a lncRNA, maternal expression gene 3 (MEG3) functions a role in mediating inflammation [ 12 ]. On the one hand, up-regulating MEG3 hampers inflammatory factor production and improves several diseases, such as rheumatoid arthritis [ 13 ], ankylosing spondylitis [ 14 ] and osteoarthritis [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

lncRNA MEG3 aggravated neuropathic pain and astrocyte overaction through mediating miR-130a-5p/CXCL12/CXCR4 axis

Dong

Xia

Zhang

et al. 2021

Aging

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Objective: Long non-coding RNAs (lncRNAs) exert a critical function in mediating neuropathic pain (NP). MEG3, a novel lncRNA, contributes to astrocyte activation and inflammation. However, its role in NP remains unclear. Methods: The chronic constriction injury (CCI) method was employed to construct an NP rat model. Astrocyte activation was induced by lipopolysaccharide (LPS). The profiles of MEG3, microRNA (miR)-130a-5p, CXC motif chemokine receptor 12 (CXCL12)/CXC motif chemokine receptor 4 (CXCR4), and the Rac1/NF-κB pathway in CCI rats’ spinal cord tissues and astrocytes were monitored by reverse transcription-quantitative PCR (RT-qPCR) and western blot (WB). Pain scores of CCI rats were assessed. Enzyme-linked immunosorbent assay (ELISA) was adopted to monitor neuroinflammation alteration. The glial fibrillary acidic protein (GFAP)-labeled astrocytes were tested by immunohistochemistry (IHC). Bioinformatics, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were utilized to verify the molecular mechanism between MEG3 and miR-130a-3p. Results: MEG3, CXCL12 and CXCR4 were overexpressed and miR-130a-5p was knocked down in CCI rats and LPS-induced astrocytes. Up-regulating MEG3 aggravated NP, enhanced inflammatory cytokines interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, and interleukin-6 (IL-6) expression and release in CCI rats and LPS-induced astrocytes. Up-regulating miR-130-5p repressed LPS-induced inflammation in astrocytes. AS verified by the dual-luciferase reporter assay and RIP assay, MEG3 sponged miR-130a-5p as a competitive endogenous RNA (ceRNA). What’s more, miR-130a-5p up-regulation weakened the MEG3-induced proinflammatory effects on LPS-induced astrocytes. Conclusions: MEG3 aggravates NP and astrocyte activation via the miR-130a-5p/CXCL12/CXCR4 axis, which is a potential therapeutic target for NP.

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“…In this review, the lncRNA/circRNA-miRNA-mRNA regulatory network also exists in microglia and astrocyte mediated neurological diseases, including SCI (Figure 1; Shao et al, 2020; FIGURE 1 | The lncRNA/circRNA-miRNA-mRNA regulatory network in microglia and astrocyte regulated neurological diseases. Xu S. et al, 2020;Zhao Q. et al, 2020;Cui et al, 2021;Xiang et al, 2021;Chen et al, 2022), TBI (He et al, 2021;Liu N. et al, 2021;Meng et al, 2021), cerebral IRI (Figure 1; Wang et al, 2020c;Yang et al, 2021), stroke (Figure 1; Qi et al, 2017;Han B. et al, 2018;Tian et al, 2021;Zhang M. et al, 2021), epilepsy (Figure 1; Feng et al, 2020;Han C. L. et al, 2020;Wan and Yang, 2020;Xiaoying et al, 2020), neuropathic pain (Figure 1; Chen M. et al, 2020), PD (Figure 1; Cao et al, 2018Cao et al, , 2021, and depression (Figure 1; . We also found that some therapies can impair the ncRNA-glial cell axis and thus inhibit disease development.…”

Section: Discussionmentioning

confidence: 99%

“…MEG3 also functions as a ceRNA for miR-7a-5p and represses miR-7a-5p inhibition on NLRP3. Functionally, MEG3 up-regulation enhances microglial activation and inflammation through the miR-7a-5p-NLRP3 axis in the TBI in vitro model (Meng et al, 2021).…”

Section: Traumatic Brain Injurymentioning

confidence: 94%

“…Nod-like receptor protein 3 (NLRP3) is a target of miR-7a-5p. NLRP3 absence decreases iNOS expression, nitric oxide (NO) production, and inflammatory cytokine (e.g., IL-1β, IL-6, and TNF-α) expression (Meng et al, 2021). LncRNA maternally expressed gene 3 (MEG3) is over-expressed in the TBI cell model (LPS + ATP induced microglial cells that are obtained from normal mice).…”

Section: Traumatic Brain Injurymentioning

confidence: 99%

See 1 more Smart Citation

Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases

Chen

Lai

Wang

et al. 2021

Front. Mol. Neurosci.

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Microglia and astrocytes maintain tissue homeostasis in the nervous system. Both microglia and astrocytes have pro-inflammatory phenotype and anti-inflammatory phenotype. Activated microglia and activated astrocytes can contribute to several neurological diseases. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), two groups of non-coding RNAs (ncRNAs), can function as competing endogenous RNAs (ceRNAs) to impair the microRNA (miRNA) inhibition on targeted messenger RNAs (mRNAs). LncRNAs and circRNAs are involved in various neurological disorders. In this review, we summarized that lncRNAs and circRNAs participate in microglia dysfunction, astrocyte dysfunction, neuron damage, and inflammation. Thereby, lncRNAs and circRNAs can positively or negatively regulate neurological diseases, including spinal cord injury (SCI), traumatic brain injury (TBI), ischemia-reperfusion injury (IRI), stroke, neuropathic pain, epilepsy, Parkinson’s disease (PD), multiple sclerosis (MS), and Alzheimer’s disease (AD). Besides, we also found a lncRNA/circRNA-miRNA-mRNA regulatory network in microglia and astrocyte mediated neurological diseases. Through this review, we hope to cast light on the regulatory mechanisms of lncRNAs and circRNAs in microglia and astrocyte mediated neurological diseases and provide new insights for neurological disease treatment.

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LncRNA-Meg3 promotes Nlrp3-mediated microglial inflammation by targeting miR-7a-5p

Cited by 52 publications

References 45 publications

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

Long non‑coding RNA nuclear paraspeckle assembly transcript 1 regulates ionizing radiation‑induced pyroptosis via microRNA‑448/gasdermin E in colorectal cancer cells

lncRNA MEG3 aggravated neuropathic pain and astrocyte overaction through mediating miR-130a-5p/CXCL12/CXCR4 axis

Long Non-coding RNAs and Circular RNAs: Insights Into Microglia and Astrocyte Mediated Neurological Diseases

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