Maternally Expressed Gene 3 (MEG3) Enhances PC12 Cell Hypoxia Injury by Targeting MiR-147

Han, Lili; Dong, Zhi-Ling; Liu, Ningning; Xie, Fei; Wang, Ning

doi:10.1159/000484452

Cited by 37 publications

(28 citation statements)

References 38 publications

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“…Abnormally expressed miRs have been proven to play an important part in diagnosis, prognosis and prediction of treatment outcome [32]. As previously reported, miR-9a-5p may provide a promising target in alleviating MCAO-induced ischemia injury; down-regulation of miR-147 was responsible for the aggravation of hypoxial injury in PC12 cells [33, 34]. Stable hsa-miR-381 expression in serum was suggested to offer a new and prospective diagnostic biomarker, and anti-hsa-miR-381 could be an ideal target for glioma treatment, further indicating that miR-381 could participate in the activities of the nervous system [15].…”

Section: Discussionmentioning

confidence: 98%

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

Piao¹,

Wu²,

Yang³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Acute cerebral ischemia is a manifestation of cerebral vascular insufficiency and has a high mortality. However, the therapy for acute cerebral ischemia is still limited. This study aimed to investigate the effect of microRNA-381 (miR-381) on the repair of nerve injury in rats with acute cerebral ischemia after cerebral lymphatic blockage (CLB) by targeting leucine-rich repeat C4 protein (LRRC4) through the Stromal cell-derived factor-1/CXC chemokine receptor-4 signaling pathway. Methods: Rat models of CLB and middle cerebral artery occlusion (MCAO) were established, and 56 Wistar rats were divided into sham, MCAO, CLB + MCAO, CLB + MCAO + miR-381 inhibitor, CLB + MCAO + miR-381 mimic, CLB + MCAO + AMD3100 and CLB + MCAO + miR-381 mimic + AMD3100 groups. Modified neurological severity score (mNSS was used to determine nerve injury, TTC staining to measure infarction volume, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining and flow cytometry to evaluate cell apoptosis, immunofluorescence to measure BrdU-positive cell number, enzyme-linked immunosorbent assay (ELISA) to determine contents of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-10 (IL-10), nerve growth factor (NGF) and neurite outgrowth inhibitor -A (Nogo-A), Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting to evaluate expression of miR-381, LRRC4, SDF-1, CXCR4, pERK, Slit2 and vascular endothelial growth factor (VEGF). Results: LRRC4 was a target gene of miR-381. Compared with the results in the CLB + MCAO group, mNSS, infarction volume, apoptosis rate and TNF-α, IL-1β, IL-6 and Nogo-A contents as well as LRRC4 expression in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups were increased (those in the CLB + MCAO + AMD3100 group > those in the CLB + MCAO + miR-381 mimic + AMD3100 group), while BrdU-positive cell number, contents of NGF and IL-10, and expression of SDF-1, CXCR4, pERK, Slit2 and VEGF in brain tissues were decreased (those in the CLB + MCAO + AMD3100 group < those in the CLB + MCAO + miR-381 mimic + AMD3100 group). The results in the CLB + MCAO + mimic group were opposite of those in the CLB + MCAO + miR-381 inhibitor and CLB + MCAO + AMD3100 groups. Conclusion: Taken together, we concluded that up-regulation of miR-381 promoted nerve injury repair in acute cerebral ischemia rats after CLB by negatively regulating LRRC4 through activating the SDF-1/CXCR4 signaling pathway.

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Section: Discussionmentioning

confidence: 98%

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

Piao¹,

Wu²,

Yang³

et al. 2018

Cell Physiol Biochem

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“…MEG3 is an imprinted gene within the DLK1-MEG3 locus located at human chromosome 14q32, which is the first lncRNA verified to act as a tumor suppressor and exert its anti-proliferative role through multiple signaling pathways [16,17,37,38]. Wei et al have revealed that MEG3 can inhibit proliferation and metastasis of gastric cancer via the p53 signaling pathway [39].…”

Section: Discussionmentioning

confidence: 99%

“…Maternally expressed gene 3 (MEG3) is the first lncRNA that has been shown to function as a tumor suppressor and inhibit cell proliferation in numerous human cancer cell lines, and it is expressed in many normal human tissues [15][16][17]. Loss of MEG3 expression has been identified in many human tumors, including cervical cancer [18], retinoblastoma [19], ovarian carcinoma [20], gastric cancer [21], germ cell tumor [22], and squamous cell carcinoma [23], and such loss is indicative of poor prognosis.…”

Section: Introductionmentioning

confidence: 99%

Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

Cui¹,

Yi²,

Xuan³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Maternally expressed gene 3 (MEG3) is an imprinted gene with maternal expression, which may function as a tumor suppressor by inhibiting angiogenesis. To identify the prognostic value of MEG3 in breast cancer, systematic analysis was performed in this study. Methods: To evaluate gene alteration during breast carcinogenesis, we explored MEG3 expression using the Serial Analysis of Gene Expression Genie suite and Oncomine analysis. The prognostic roles of MEG3 in breast cancer were investigated using the PrognoScan database. The heat map and methylation status of MEG3 were determined using the UCSC Genome Browser. Results: We found that MEG3 was more frequently downregulated in breast cancer than in normal tissues and this correlated with prognosis. However, estrogen receptor and progesterone receptor status were found to be positively correlated with MEG3 expression. Conversely, basal-like status, triple-negative breast cancer status, and Scarff Bloom & Richardson grade criterion were negatively correlated with MEG3 expression. Following data mining in multiple big data databases, we confirmed a positive correlation between MEG3 and heparan sulfate proteoglycan 2 (HSPG2) expression in breast cancer tissues. Conclusion: MEG3 could be adopted as a marker to predict the prognosis of breast cancer with HSPG2. However, large-scale and comprehensive research is needed to clarify our results.

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“…One possible explanation of this is that there might be an unknown gene that is targeted by miR-147, and the effect of MEG3 and miR-147 on cell apoptosis might be mediated by this gene [30]. For example, Han et al, found that MEG3 aggravated hypoxia injury in PC12 cells by down-regulating miR-147, and miR-147 further negatively regulated Sox2 expression [31]. It should be noted that our co-immunoprecipitation results showed that JAK2 could interact with TYK2 through MEG3, suggesting that JAK2 might be the gene contributing to the negative interaction between MEG3 and mi147.…”

Section: Discussionmentioning

confidence: 99%

The Long Noncoding RNA MEG3 and its Target miR-147 Regulate JAK/STAT Pathway in Advanced Chronic Myeloid Leukemia

Yang

Liu

et al. 2018

EBioMedicine

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BackgroundLong non-coding (lnc) RNAs plays an important role in chronic myeloid leukemia (CML). In this study, we aimed to uncover the mechanism of the lncRNA maternally expressed 3 (MEG3) and its target microRNA-147 (miR-147) in CML.MethodsSixty CML patients and 10 healthy donors were included in the study. The methylation of MEG3 and miR-147 promoter was determined by methylation-specific PCR. The relationship of MEG3 and miR-147 was explored by luciferase assay. The interactions of proteins were studied by RNA pull-down assay, RNA immunoprecipitation and co-immunoprecipitation.FindingsPatients in accelerated phase CML (CML-AP) and blast phase CML (CML-BP) showed lower expressions of MEG3 and miR-147 and higher expressions of DNMT1, DNMT3B, MBD2, MECP2 and HDAC1 compared to the controls. These patients also showed a higher degree of methylation of MEG3 and miR-147 while there was a reduction after chidamide treatment. Furthermore, the overexpression of MEG3 and miR-147 inhibited cell proliferation both in vivo and in vitro, promoted apoptosis and decreased the expressions of DNMT1, DNMT3A, DNMT3B, MBD2, HDAC1 and MECP2. We also found MEG3 interacted with DNMT1, JAK2, STAT3, HDAC1, and TYK2, and JAK2 was bound to STAT3, STAT5 and MYC. More interestingly, JAK2 was bound to TYK2 by the bridge of MEG3.InterpretationLncRNA MEG3 and its target miR-147 may serve as a novel therapeutic target for CML blast crisis, and chidamide might have a potential clinical application in treating CML blast crisis.

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Maternally Expressed Gene 3 (MEG3) Enhances PC12 Cell Hypoxia Injury by Targeting MiR-147

Cited by 37 publications

References 38 publications

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

MicroRNA-381 Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4 Signaling Pathway via LRRC4 in Acute Cerebral Ischemia after Cerebral Lymphatic Blockage

Mining Prognostic Significance of MEG3 in Human Breast Cancer Using Bioinformatics Analysis

The Long Noncoding RNA MEG3 and its Target miR-147 Regulate JAK/STAT Pathway in Advanced Chronic Myeloid Leukemia

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