H19X-encoded miR-424(322)/-503 cluster: emerging roles in cell differentiation, proliferation, plasticity and metabolism

Wang, Fan; Ling, Rui; Tandon, Neha; Matthews, Elizabeth Renee; Shrestha, Som Kumar; Jiao, Yang; Soibam, Benjamin; Yang, Jin; Liu, Yu

doi:10.1007/s00018-018-2971-0

Cited by 55 publications

(49 citation statements)

References 153 publications

(151 reference statements)

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“…This miRNA cluster includes six miRNAs (miR‐424, miR‐503, miR‐542, miR‐450a‐1, miR‐450a‐2, and miR‐450b) and has postulated roles in cell differentiation, proliferation, plasticity, and metabolism, extensively reviewed by Wang et al . . In accordance to our data, members of this miRNA cluster were previously found to be increased in the skeletal muscle of patients with other muscle wasting diseases: in patients with amyotrophic lateral sclerosis, the expression levels of miR‐425, miR‐450b, miR‐503, and miR‐542 were increased .…”

Section: Discussionsupporting

confidence: 92%

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia

Worp

Schols

Dingemans

et al. 2019

J cachexia sarcopenia muscle

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Background Cachexia, highly prevalent in patients with non-small cell lung cancer (NSCLC), impairs quality of life and is associated with reduced tolerance and responsiveness to cancer therapy and decreased survival. MicroRNAs (miRNAs) are small non-coding RNAs that play a central role in post-transcriptional gene regulation. Changes in intramuscular levels of miRNAs have been implicated in muscle wasting conditions. Here, we aimed to identify miRNAs that are differentially expressed in skeletal muscle of cachectic lung cancer patients to increase our understanding of cachexia and to allow us to probe their potential as therapeutic targets. Methods A total of 754 unique miRNAs were profiled and analysed in vastus lateralis muscle biopsies of newly diagnosed treatment-naïve NSCLC patients with cachexia (n = 8) and age-matched and sex-matched healthy controls (n = 8). miRNA expression analysis was performed using a TaqMan MicroRNA Array. In silico network analysis was performed on all significant differentially expressed miRNAs. Differential expression of the top-ranked miRNAs was confirmed using reverse transcriptionquantitative real-time PCR in an extended group (n = 48) consisting of NSCLC patients with (n = 15) and without cachexia (n = 11) and healthy controls (n = 22). Finally, these miRNAs were subjected to univariate and multivariate Cox proportional hazard analysis using overall survival and treatment-induced toxicity data obtained during the follow-up of this group of patients. Results We identified 28 significant differentially expressed miRNAs, of which five miRNAs were up-regulated and 23 were down-regulated. In silico miRNA-target prediction analysis showed 158 functional gene targets, and pathway analysis identified 22 pathways related to the degenerative or regenerative processes of muscle tissue. Subsequently, the expression of six topranked miRNAs was measured in muscle biopsies of the entire patient group. Five miRNAs were detectable with reverse transcription-quantitative real-time PCR analysis, and their altered expression (expressed as fold change, FC) was confirmed in muscle of cachectic NSCLC patients compared with healthy control subjects: miR-424-5p (FC = 4.5), miR-424-3p (FC = 12), miR-450a-5p (FC = 8.6), miR-144-5p (FC = 0.59), and miR-451a (FC = 0.57). In non-cachectic NSCLC patients, only miR-424-3p was significantly increased (FC = 5.6) compared with control. Although the statistical support was not sufficient to imply these miRNAs as individual predictors of overall survival or treatment-induced toxicity, when combined in multivariate analysis, miR-450-5p and miR-451a resulted in a significant stratification between short-term and long-term survival. Conclusions We identified differentially expressed miRNAs putatively involved in lung cancer cachexia. These findings call for further studies to investigate the causality of these miRNAs in muscle atrophy and the mechanisms underlying their differential expression in lung cancer cachexia.

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Section: Discussionsupporting

confidence: 92%

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia

Worp

Schols

Dingemans

et al. 2019

J cachexia sarcopenia muscle

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“…Such unusual genomic arrangements of the miRNAs intensively raise our attention to explore their possible regulatory functions. For example, the MIR1306 gene overlaps the DGCR8 coding region and the MIR675 gene is embedded in the first exon of H19 lncRNA, both of which are conserved in primates ( Morin et al, 2008 ; Friedländer et al, 2008 ; Keniry et al, 2012 ; Wang et al, 2018 ). It has been reported that the mir-1306 hairpin is cleaved by the Drosha-DGCR8 complex, which plays an important negative-feedback role in controlling DGCR8 expression ( Morin et al, 2008 ; Friedländer et al, 2008 ; Keniry et al, 2012 ; Wang et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

“…For example, the MIR1306 gene overlaps the DGCR8 coding region and the MIR675 gene is embedded in the first exon of H19 lncRNA, both of which are conserved in primates ( Morin et al, 2008 ; Friedländer et al, 2008 ; Keniry et al, 2012 ; Wang et al, 2018 ). It has been reported that the mir-1306 hairpin is cleaved by the Drosha-DGCR8 complex, which plays an important negative-feedback role in controlling DGCR8 expression ( Morin et al, 2008 ; Friedländer et al, 2008 ; Keniry et al, 2012 ; Wang et al, 2018 ). H19 is an important imprinted gene involved in placental development prior to birth, which limits the growth of the placenta by regulating miR-675 processes ( Keniry et al, 2012 ; Wang et al, 2018 ; Han et al, 2009 ).…”

Section: Discussionmentioning

confidence: 99%

Analysis of conserved miRNAs in cynomolgus macaque genome using small RNA sequencing and homology searching

Huang

Liu³

et al. 2020

PeerJ

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MicroRNAs (miRNAs) are important regulators that fine-tune diverse cellular activities. Cynomolgus macaques (Macaca fascicularis) are used extensively in biomedical and pharmaceutical research; however, substantially fewer miRNAs have been identified in this species than in humans. Consequently, we investigated conserved miRNA profiles in cynomolgus macaques by homology searching and small RNA sequencing. In total, 1,455 high-confidence miRNA gene loci were identified, 408 of which were also confirmed by RNA sequencing, including 73 new miRNA loci reported in cynomolgus macaques for the first time. Comparing miRNA expression with age, we found a positive correlation between sequence conservation and expression levels during miRNA evolution. Additionally, we found that the miRNA gene locations in cynomolgus macaque genome were very flexible. Most were embedded in intergenic spaces or introns and clustered together. Several miRNAs were found in certain gene locations, including 64 exon-resident miRNAs, six splice-site-overlapping miRNAs (SO-miRNAs), and two pairs of distinct mirror miRNAs. We also identified 78 miRNA clusters, 68 of which were conserved in the human genome, including 10 large miRNA clusters predicted to regulate diverse developmental and cellular processes in cynomolgus macaque. Thus, this study not only expands the number of identified miRNAs in cynomolgus macaques but also provides clues for future research on the differences in miRNA repertoire between macaques and humans.

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“…Long non-coding RNA (lncRNA) is a member of the RNA family, with length of more than 200 nucleotides. In recent years, numerous studies have approved lncRNA involved in biological processes including proliferation, differentiation and apoptosis [13][14][15]. X-inactive specific transcript (XIST) is a dramatic example of lncRNA, which plays a key role in silencing of X-chromosome [16].…”

Section: Introductionmentioning

confidence: 99%

Promoter polymorphisms in the lncRNA-MIAT gene associated with acute myocardial infarction in Chinese Han population: a case–control study

Zhu

et al. 2020

Bioscience Reports

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Background: Coronary atherosclerotic disease (CAD) is one of the greatest causes of death and disability around the world, and has emerged as a major public health problem. Acute myocardial infarction (AMI) is the most serious type of CAD. Myocardial infarction (MI) association transcript (MIAT) has demonstrated that it plays an important role in AMI. Purpose: To investigate the association between MIAT promoter polymorphisms and AMI in Chinese Han population. Methods: A total of 212 AMI patients and 218 healthy controls were recruited. The long non-coding RNA (lncRNA)-MIAT promoter polymorphisms (single nucleotide polymorphisms (SNPs)) were obtained using polymerase chain reaction (PCR) and sequencing techniques. Chi-square test was used to analyze the allele and genotype frequencies of each SNP in two groups. Logistic regression analysis was used to analyze the association of each SNP with AMI. Linkage disequilibrium (LD) and haplotype analysis were performed using SHEsis software. A JASPAR database search predicts transcription factors transition of linked polymorphism in MIAT promoter. Results: Ten SNPs were found, including rs56371714, rs55892869, rs151057042, rs2157598, rs150465374, rs5761664, rs8142890, rs5752375, rs9608515 and rs1055293700, whereas rs1055293700 was found only in the control group. Single and logistic regression analysis showed that there was a significant correlation between rs5752375 and rs9608515 polymorphisms and AMI, while other sites had no relationship with AMI. These MI association polymorphisms may change the binding sites with transcription factor. Conclusions: The polymorphisms of lncRNA-MIAT promoter rs5752375 and rs9608515 were significantly associated with AMI in Chinese Han population. This result would be of clinical importance for the early diagnosis of AMI.

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H19X-encoded miR-424(322)/-503 cluster: emerging roles in cell differentiation, proliferation, plasticity and metabolism

Cited by 55 publications

References 153 publications

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia

Identification of microRNAs in skeletal muscle associated with lung cancer cachexia

Analysis of conserved miRNAs in cynomolgus macaque genome using small RNA sequencing and homology searching

Promoter polymorphisms in the lncRNA-MIAT gene associated with acute myocardial infarction in Chinese Han population: a case–control study

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