Long non-coding RNA MIAT in development and disease: a new player in an old game

Sun, Chengyi; Huang, Liyi; Li, Zhenglong; Leng, Kaiming; Xu, Yi; Jiang, Xingming; Cui, Yunfu

doi:10.1186/s12929-018-0427-3

Cited by 96 publications

(82 citation statements)

References 63 publications

(70 reference statements)

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“…Long noncoding RNAs (lncRNAs) are RNA transcripts longer than 200 nucleotides which, although not having the function of direct coding proteins, can regulate the expression of genes at transcriptional, post-transcriptional, and translational levels [4,5]. MIAT, also termed as Gomafu in human or Rncr2 in mouse [6][7][8], is a promising functional factor among all disease-associated lncRNAs, and exhibits deregulation in multiple diseases, including upregulation in ischemic stroke, myocardial infarction, neuroendocrine prostate cancer, non-small-cell lung cancer, diabetic cardiomyopathy, cataract, chronic chagas disease cardiomyopathy, chronic lymphocytic leukemia and down-regulation in schizophrenia, diabetic nephropathy, bone disease [9]. It has recently found that MIAT is upregulated in hearts of a mouse model of AMI, and knocking it down improves cardiac function by inhibition of activation of NF-κB signaling pathway [10].…”

Section: Introductionmentioning

confidence: 99%

Targeting MIAT reduces apoptosis of cardiomyocytes after ischemia/reperfusion injury

Chen¹,

Zhang²,

Yu³

et al. 2019

Bioengineered

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This study aims to investigate the role of targeting lncRNA myocardial infarction-associated transcript (MIAT) in protection against hypoxia/reoxygenation (H/R) injury in H9c2 cells in vitro and myocardial ischemia/reperfusion (I/R) injury in vivo by regulating expression of NF-kB and p53 upregulated modulator of apoptosis (PUMA). H9C2 cells were infected with lentivirus expressing the short-hairpin RNA direct against human MIAT gene (Lv-MIAT shRNA) or lentivirus expressing scrambled control (Lv-NC shRNA) or PUMA siRNA or p65 siRNA or their control siRNA respectively. Then the H9c2 cells were infected with Lv-shRNA to 2 hours of hypoxia (H) and 24 hour of reoxygenation (R). 100 ul of Lv-MIAT shRNA (1 × 10 8 PFU) or Lv-NC shRNA was transfected into mouse hearts, then the hearts were subjected to I/R (1h/72 h). We discovered targeting MIAT remarkably enhanced H9c2 cell viability, decreased H/R-induced cell apoptosis and LDH leakage and significantly decreased I/R-induced myocardial infarct size, reduced myocardial apoptosis and enhanced the heart function. Targeting MIAT downregulated p65 nuclear translocation, NF-κB activity and anti-apoptotic protein cleaved-caspase-3, Bax, and upregulated anti-apoptotic protein Bcl-2 induced by H/R or I/R. Our study suggests that targeting MIAT may protect against H9c2 cardiomyoblasts H/R injury or myocardial I/R injury via inhibition of cell apoptosis, mediated by NF-κB and PUMA signal pathway. ARTICLE HISTORY

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Section: Introductionmentioning

confidence: 99%

Targeting MIAT reduces apoptosis of cardiomyocytes after ischemia/reperfusion injury

Chen¹,

Zhang²,

Yu³

et al. 2019

Bioengineered

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“…Association between circulating lncRNAs relative expression levels and the clinical and laboratory data in β-thalassemia patients (n = 50). lymphocytic leukemia and non-Hodgkin's lymphoma [22]. Consistent with the regulatory loop MIAT constitute with OCT4 (octamer-binding transcription factor 4) in mouse embryonic stem cells [45], the latter research group has shown a similar loop in lymphoma and has identified that both MIAT and OCT4 were essential for cell survival [22].…”

Section: Discussionmentioning

confidence: 89%

“…The lncRNA MIAT, also termed as Gomafu; the mouse homologue of MIAT, is an emerging functional player among all disease-related lncRNAs and is expressed in various tissues, including muscle, blood, nervous and retinal tissues, and exhibits deregulation in multiple diseases [44]. Nearly no studies are available to date on the expression level of MIAT in peripheral blood from patients with thalassemia.…”

Section: Discussionmentioning

confidence: 99%

“…Because of its physical interaction with the splicing factor 1 (SF1) via SF1binding motif, it was speculated to be involved in RNA splicing and to exert a regulatory effect on gene expression [20]. Furthermore, it was supposed to function as a competing endogenous RNA (ceRNA) to regulate the VEGF (vascular endothelial growth factor) levels by sponging the microRNA miR-150-5p, creating MIAT/miR-150-5p/VEGF loop that was implicated in microvascular dysfunction and other disorders [21,22].…”

Section: Introductionmentioning

confidence: 99%

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Long non-coding RNAs MALAT1, MIAT and ANRIL gene expression profiles in beta-thalassemia patients: a cross-sectional analysis

2019

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Objectives: Beta-thalassemia (β-thal) is one of the most common genetic disorders worldwide. Multiple genetic and epigenetic mechanisms could be implicated in the pathogenesis and/or phenotype variations. We sought to explore the serum expression profile of three diseaserelated long non-coding RNAs (lncRNAs) in a sample of Egyptian β-thal patients with correlation to the patients' clinicolaboratory data. Methods: Fifty consecutive β-thal patients and 50 unrelated controls were enrolled in the study. Quantification of circulating lncRNAs; MALAT1 (metastasis-associated lung adenocarcinoma transcript 1), MIAT (myocardial infarction associated transcript), and ANRIL (antisense noncoding RNA in the INK4 locus) was done by Real-time qRT-PCR. Results: Significant higher expression levels of the studied lncRNAs in β-thal patients compared to the controls (all P values < 0.001) were identified. There was no significant difference between β-thal-major and intermedia patients at the level of any of the studied lncRNAs. Higher MALAT1 expression profile was associated with early age at onset, early age at first blood transfusion, and a higher frequency of splenomegaly. Whereas, up-regulated MIAT levels were associated with early age at first blood transfusion. Conclusions: Taken together, the studied lncRNAs MALAT1, MIAT, and ANRIL might be implicated in β-thal pathogenesis and could provide new molecular biomarkers for β-thalassemia after validation in large-scale future studies.

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“…Out of this pool of STAiRs, we focused on STAiR18 for the following reasons: In contrast to the unprocessed macroRNAs STAiR1, − 2 and − 6, STAiR15 and − 18 were spliced and therefore suited better to carry out functional analyses by siRNAbased knockdown strategies. Moreover, at the time we identified the STAiRs, STAiR15 (alias MIAT) was already described in great detail [9,10] in contrast to STAiR18. Most importantly, only STAiR18 showed a global overexpression in various cancer types [8].…”

Section: Introductionmentioning

confidence: 98%

Master and servant: LINC00152 – a STAT3-induced long noncoding RNA regulates STAT3 in a positive feedback in human multiple myeloma

et al. 2020

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Background: The survival of INA-6 human multiple myeloma cells is strictly dependent upon the Interleukin-6activated transcription factor STAT3. Although transcriptional analyses have revealed many genes regulated by STAT3, to date no protein-coding STAT3 target gene is known to mediate survival in INA-6 cells. Therefore, the aim here was to identify and analyze non-protein-coding STAT3 target genes. In addition to the oncogenic microRNA-21, we previously described five long noncoding RNAs (lncRNAs) induced by STAT3, named STAiRs. Here, we focus on STAT3-induced RNA 18 (STAiR18), an mRNA-like, long ncRNA that is duplicated in the human lineage. One STAiR18 locus is annotated as the already well described LINC00152/CYTOR, however, the other harbors the MIR4435-2HG gene and is, up to now, barely described.Methods: CAPTURE-RNA-sequencing was used to analyze STAiR18 transcript architecture. To identify the STAiR18 and STAT3 phenotype, siRNA-based knockdowns were performed and microarrays were applied to identify their target genes. RNA-binding partners of STAiR18 were determined by Chromatin-Isolation-by-RNA-Purification (ChIRP) and subsequent sequencing. STAT3 expression in dependence of STAiR18 was investigated by immunoblots, chromatin-and RNA-immunoprecipitations. Results: As identified by CAPTURE-RNA sequencing, a complex splice pattern originates from both STAiR18 loci, generating different transcripts. Knockdown of the most abundant STAiR18 isoforms dramatically decreased INA-6 cell vitality, suggesting a functional role in myeloma cells. Additionally, STAiR18 and STAT3 knockdowns yielded overlapping changes of transcription patterns in INA-6 cells, suggesting a close functional interplay between the two factors. Moreover, Chromatin isolation by RNA purification (ChIRP), followed by genome-wide RNA sequencing showed that STAiR18 associates specifically with the STAT3 primary transcript. Furthermore, the knockdown of STAiR18 reduced STAT3 levels on both the RNA and protein levels, suggesting a positive feedback between both molecules. Furthermore, STAiR18 knockdown changes the histone methylation status of the STAT3 locus, which explains the positive feedback and indicates that STAiR18 is an epigenetic modulator.

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Long non-coding RNA MIAT in development and disease: a new player in an old game

Cited by 96 publications

References 63 publications

Targeting MIAT reduces apoptosis of cardiomyocytes after ischemia/reperfusion injury

Targeting MIAT reduces apoptosis of cardiomyocytes after ischemia/reperfusion injury

Long non-coding RNAs MALAT1, MIAT and ANRIL gene expression profiles in beta-thalassemia patients: a cross-sectional analysis

Master and servant: LINC00152 – a STAT3-induced long noncoding RNA regulates STAT3 in a positive feedback in human multiple myeloma

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