MicroRNA 329 Suppresses Angiogenesis by Targeting CD146

Wang, Ping; Luo, Yongting; Duan, Hongxia; Xing, Shu; Zhang, Jianlin; Lu, Di; Feng, Jing; Yang, Di; Song, Lina; Yan, Xiyun

doi:10.1128/mcb.00343-13

Cited by 65 publications

(62 citation statements)

References 49 publications

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“…Among the miRs, miR-411 regulates myogenesis by targeting myogenic factors (39), and miR-494 regulates the mitochondrial biogenesis of skeletal muscle by targeting mitochondrial transcription factor A and Forkhead box j3 (40). MiR-329 can inhibit cell proliferation and angiogenesis in vitro by targeting E2F and KDM1A (41,42). We measured the expression of E2F, KDMIA, and other target proteins of the miR-379/miR-544 cluster in neonatal mice and found no apparent change that was consistent with the expression of the transcripts of this cluster (Fig.…”

Section: Discussionmentioning

confidence: 99%

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Gao

Chen

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Inheritance of the callipyge phenotype in sheep is an example of polar overdominance inheritance, an unusual mode of inheritance. To investigate the underlying molecular mechanism, we profiled the expression of the genes located in the Delta-like 1 homolog (Dlk1)-type III iodothyronine deiodinase (Dio3) imprinting region in mice. We found that the transcripts of the microRNA (miR) 379/miR-544 cluster were highly expressed in neonatal muscle and paralleled the expression of the Dlk1. We then determined the in vivo role of the miR-379/miR-544 cluster by establishing a mouse line in which the cluster was ablated. The maternal heterozygotes of young mutant mice displayed a hypertrophic tibialis anterior muscle, extensor digitorum longus muscle, gastrocnemius muscle, and gluteus maximus muscle and elevated expression of the DLK1 protein. Reduced expression of DLK1 was mediated by miR-329, a member of this cluster. Our results suggest that maternal expression of the imprinted miR-379/miR-544 cluster regulates paternal expression of the Dlk1 gene in mice. We therefore propose a miR-based molecular working model for polar overdominance inheritance. muscle hypertrophy | callipyge | DLK1 | miR-379/miR-544 cluster T he callipyge (CLPG) phenotype can be characterized by an increase in muscle mass due to muscular hypertrophy and a unique non-Mendelian mode of inheritance (1-3). CLPG individuals are born with normal muscle histology and develop muscle hypertrophy at ∼1 mo of age. This hypertrophy occurs primarily in the muscles of the pelvic limbs and loin and some muscles in the shoulder, which are enriched with a high proportion of type IIB fast-twitch glycolytic fibers (4). Although the molecular regulation of these hypertrophic processes is yet to be determined, Delta-like 1 homolog (DLK1) is found to be the causative protein (5-10). The unique mode of inheritance of the CLPG phenotype has attracted a great deal of attention within the scientific community. The CLPG offspring inherit the phenotype only when the mutated allele comes from the father and the wild-type allele from the mother (CLPG PAT /+ MAT ). CLPG PAT /CLPG MAT offspring exhibit a wild-type phenotype, despite carrying a CLPG mutation on the paternal chromosome. This unusual mode of inheritance led to the development of the genetic concept of polar overdominance (2, 11).The CLPG mutation has been mapped to the Dlk1-Dio3 imprinted domain, which spans ∼1 Mb and harbors at least three protein-encoding genes, including Dlk1, Peg11/Rtl1, and Dio3, and multiple noncoding RNA genes, including Gtl2, anti-Peg11/anti-Rtl1, Meg8, Mirg, C/D small nucleolar RNAs (snoRNAs), and microRNA clusters [the microRNA (miR) 379 and miR-127 clusters] (12-14). The coding genes are expressed paternally, whereas the noncoding genes are expressed maternally (15,16). Further analysis revealed a point mutation (A to G transition) within the intergenic region between the Dlk1 and Gtl2 genes of the imprinted Dlk1-Dio3 region (17, 18), which affects a muscle-specific, long-range cis-acting ...

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Section: Discussionmentioning

confidence: 99%

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Gao

Chen

Wang

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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“…Other studies have shown differential expression of miR-362-3p in various tissues including the fetal brain of mice, estrogen receptor-positive breast tumors, gastric cancer, and melanoma as well as downregulation of miR-329 in glioma, neuroblastoma, and the mouse model of Rett syndrome. 20,22,29,[33][34][35][36][37][38] The detailed mechanism, however, that governs the differential expression of the two miRs has not been fully elucidated.…”

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confidence: 99%

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Kang

et al. 2015

Cell Death Differ

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p130Cas regulates cancer progression by driving tyrosine receptor kinase signaling. Tight regulation of p130Cas expression is necessary for survival, apoptosis, and maintenance of cell motility in various cell types. Several studies revealed that transcriptional and post-translational control of p130Cas are important for maintenance of its expression and activity. To explore novel regulatory mechanisms of p130Cas expression, we studied the effect of microRNAs (miRs) on p130Cas expression in human breast cancer MCF7 cells. Here, we provide experimental evidence that miR-362-3p and miR-329 perform a tumor-suppressive function and their expression is downregulated in human breast cancer. miR-362-3p and miR-329 inhibited cellular proliferation, migration, and invasion, thereby suppressing tumor growth, by downregulating p130Cas. Ectopic expression of p130Cas attenuated the inhibitory effects of the two miRs on tumor progression. Relative expression levels of miR-362-3p/329 and p130Cas between normal and breast cancer correlated inversely; miR-362-3p/329 expression was decreased, whereas that of p130Cas increased in breast cancers. Furthermore, we showed that downregulation of miR-362-3p and miR-329 was caused by differential DNA methylation of miR genes. Enhanced DNA methylation (according to methylation-specific PCR) was responsible for downregulation of miR-362-3p and miR-329 in breast cancer. Taken together, these findings point to a novel role for miR-362-3p and miR-329 as tumor suppressors; the miR-362-3p/miR-329-p130Cas axis seemingly has a crucial role in breast cancer progression. Thus, modulation of miR-362-3p/miR-329 may be a novel therapeutic strategy against breast cancer. Cell Death and Differentiation (2016) 23, 484-495; doi:10.1038/cdd.2015; published online 4 September 2015 p130Cas/breast cancer anti-estrogen resistance 1 is a member of the Cas (Crk-associated substrate) family of adaptor proteins and has a central role in tyrosine kinasebased signaling related to cell adhesion, migration, cell cycle control, apoptosis, development, and cancer progression.

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“…CD146 has been identified as an adhesion molecule expressed at the intercellular junction of endothelial cells [15]. More recently, CD146 was found to be involved in endothelial cell activity and angiogenesis [37][38][39]. The membrane glycoprotein CD146 is rarely found in the blood of healthy subjects, while a soluble form of CD146, which is generated probably by extracellular shedding, proteolysis or DNA splicing from damaged endothelium, was confirmed to be increased in the peripheral circulation of patients with tumor [22], inflammatory diseases [20] or CKD [18], suggesting a pivotal role of this soluble biomarker in the pathogenesis of angiogenesis and vascular endothelial alteration.…”

Section: Discussionmentioning

confidence: 99%

Expression of Endothelial Cell Injury Marker Cd146 Correlates with Disease Severity and Predicts the Renal Outcomes in Patients with Diabetic Nephropathy

Fan

Yang

Li³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Glomerular endothelial cell injury plays a crucial role in the development of diabetic nephropathy (DN). CD146, an endothelial marker, was shown to increase in chronic kidney disease (CKD), but its role in DN remains unknown. We aim to assess whether CD146 could be used to evaluate disease severity and predict renal outcomes in DN at early stages. Methods: 159 non-dialysis type 2-DN patients from 2008 to 2015 were enrolled to measure the plasma concentration of soluble CD146 (sCD146). 94 type 2 diabetes mellitus patients without DN and 100 healthy subjects were used as controls. The patients with CKD stage 1-3 were referred as early stage patients. Another independent cohort of 48 patients with biopsy-proved DN was used for the immunohistochemistry study of CD146. Renal outcomes were defined as doubling of serum creatinine, initiation of renal replacement therapy or death. Results: We found that plasma level of sCD146 was upregulated and associated with renal function in DN patients. sCD146 was proved to be a more optimal marker than urine albumin creatinine ratio to evaluate disease severity in these DN patients. The kidney expression of CD146 was co-localized with endothelial marker CD31 and increased in DN. CD146 staining in kidney was correlated with the severity of pathological changes in DN patients. Survival analysis suggested that both plasma and biopsy expression of CD146 were correlated with renal outcomes. Conclusions: CD146 is associated with kidney injury and could be a good marker to predict renal outcomes in patients with early stages of DN.

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MicroRNA 329 Suppresses Angiogenesis by Targeting CD146

Cited by 65 publications

References 49 publications

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Regulation of DLK1 by the maternally expressed miR-379/miR-544 cluster may underlie callipyge polar overdominance inheritance

Downregulation of microRNA-362-3p and microRNA-329 promotes tumor progression in human breast cancer

Expression of Endothelial Cell Injury Marker Cd146 Correlates with Disease Severity and Predicts the Renal Outcomes in Patients with Diabetic Nephropathy

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