Downregulation of long non-coding RNA H19 promotes P19CL6 cells proliferation and inhibits apoptosis during late-stage cardiac differentiation via miR-19b-modulated Sox6
Abstract:BackgroundRegulating cardiac differentiation to maintain normal heart development and function is very important. At present, biological functions of H19 in cardiac differentiation is not completely clear.MethodsTo explore the functional effect of H19 during cardiac differentiation. Expression levels of early cardiac-specific markers Nkx-2.5 and GATA4, cardiac contractile protein genes α-MHC and MLC-2v were determined by qRT-PCR and western lot. The levels of lncRNA H19 and miR-19b were detected by qRT-PCR. We… Show more
“…During the late stage of cardiac differentiation of P19CL6 cells, miR‐19b was negatively regulated by H19, as demonstrated by luciferase activity assay and qRT‐PCR. The overexpression of H19 significantly inhibited cell proliferation and promoted cell apoptosis via modulating miR‐19b and its target sox6, while the down‐regulation of H19 reversed these effects …”
Section: Lncrna As Mirna Sponges In Regulating the Biological Activitmentioning
confidence: 99%
“…It has been gradually demonstrated that H19 may modulate a variety of cell biological functions by sequestering different miRNAs; H19 can serve as not only as a sponge of miRNAs, such as let‐7, miR‐103/107 and miR‐19b, in cell differentiation, necrosis and proliferation, but also as a precursor of miRNAs in the regulation of cardiomyocyte hypertrophy. The miR‐675 was validated to be located in the first exon of H19, and both H19 and miR‐675 were up‐regulated in hypertrophic heart tissue.…”
Section: Coexpression Of Lncrnas With Mirna In Modulating the Biologimentioning
confidence: 99%
“…The overexpression of H19 significantly inhibited cell proliferation and promoted cell apoptosis via modulating miR-19b and its target sox6, while the down-regulation of H19 reversed these effects. 32 Cardiomyocyte autophagy is an evolutionarily conserved process in face of stress stimuli, but abnormal autophagy contributes to cell death. 33 The lncRNA AK079427, named APF, played a crucial role in the regulation of cardiomyocyte autophagy by modulating miR-188-3p and its target ATG7.…”
Section: Regulating the Biological Activities Of Cardiomyocyte S Andmentioning
Long noncoding RNAs (lncRNAs) are RNAs longer than 200 nt in length that are characterized by low levels of sequence conservation and expression; lncRNAs modulate various biological functions at epigenetic, transcriptional and post‐transcriptional levels, or directly regulate protein activity. As a family of small and evolutionarily conserved noncoding RNAs, microRNAs (miRNAs) are capable of regulating physiological and pathological processes via inhibiting target mRNA translation or promoting mRNA degradation. A number of studies have confirmed that both lncRNAs and miRNAs are closely associated with the development of cardiovascular diseases (CVDs), such as cardiac remodelling, heart failure, myocardial injury and arrhythmia, and that they act as biomarkers, potential therapeutic targets or strong indicators of prognosis; however, the underlying molecular mechanism has not been elucidated. Recently, emerging evidence showed that the novel regulatory mechanism underlying the crosstalk among lncRNAs, miRNAs and mRNAs plays a pivotal role in the pathophysiological processes of CVDs in response to stress stimuli. In this review, I comprehensively summarized the regulatory relationship of lncRNAs, miRNAs and mRNAs and highlighted the important role of the lncRNA‐miRNA‐mRNA axis in CVDs.
“…During the late stage of cardiac differentiation of P19CL6 cells, miR‐19b was negatively regulated by H19, as demonstrated by luciferase activity assay and qRT‐PCR. The overexpression of H19 significantly inhibited cell proliferation and promoted cell apoptosis via modulating miR‐19b and its target sox6, while the down‐regulation of H19 reversed these effects …”
Section: Lncrna As Mirna Sponges In Regulating the Biological Activitmentioning
confidence: 99%
“…It has been gradually demonstrated that H19 may modulate a variety of cell biological functions by sequestering different miRNAs; H19 can serve as not only as a sponge of miRNAs, such as let‐7, miR‐103/107 and miR‐19b, in cell differentiation, necrosis and proliferation, but also as a precursor of miRNAs in the regulation of cardiomyocyte hypertrophy. The miR‐675 was validated to be located in the first exon of H19, and both H19 and miR‐675 were up‐regulated in hypertrophic heart tissue.…”
Section: Coexpression Of Lncrnas With Mirna In Modulating the Biologimentioning
confidence: 99%
“…The overexpression of H19 significantly inhibited cell proliferation and promoted cell apoptosis via modulating miR-19b and its target sox6, while the down-regulation of H19 reversed these effects. 32 Cardiomyocyte autophagy is an evolutionarily conserved process in face of stress stimuli, but abnormal autophagy contributes to cell death. 33 The lncRNA AK079427, named APF, played a crucial role in the regulation of cardiomyocyte autophagy by modulating miR-188-3p and its target ATG7.…”
Section: Regulating the Biological Activities Of Cardiomyocyte S Andmentioning
Long noncoding RNAs (lncRNAs) are RNAs longer than 200 nt in length that are characterized by low levels of sequence conservation and expression; lncRNAs modulate various biological functions at epigenetic, transcriptional and post‐transcriptional levels, or directly regulate protein activity. As a family of small and evolutionarily conserved noncoding RNAs, microRNAs (miRNAs) are capable of regulating physiological and pathological processes via inhibiting target mRNA translation or promoting mRNA degradation. A number of studies have confirmed that both lncRNAs and miRNAs are closely associated with the development of cardiovascular diseases (CVDs), such as cardiac remodelling, heart failure, myocardial injury and arrhythmia, and that they act as biomarkers, potential therapeutic targets or strong indicators of prognosis; however, the underlying molecular mechanism has not been elucidated. Recently, emerging evidence showed that the novel regulatory mechanism underlying the crosstalk among lncRNAs, miRNAs and mRNAs plays a pivotal role in the pathophysiological processes of CVDs in response to stress stimuli. In this review, I comprehensively summarized the regulatory relationship of lncRNAs, miRNAs and mRNAs and highlighted the important role of the lncRNA‐miRNA‐mRNA axis in CVDs.
“…It also provides miR‐Function and ceRNA‐Function web tools to predict the function of ncRNAs (miRNAs, lncRNAs, pseduogenes) and protein‐coding genes from the miRNA‐mediated (ceRNA) regulatory networks . StarBase was commonly used in studying lncRNA‐miRNA‐mRNA network …”
PTEN pseudogene (PTENP1) has a tumor suppressive role in multiple cancers. However, its involvement in esophageal squamous cell carcinoma (ESCC) remains largely unknown. In this study, we set out to identify the role of PTENP1 in the development of ESCC. Gene Expression Omnibus database was employed to investigate the expression of PTENP1 in ESCC. sRNA target Database (StarBase v2.0) was used to query the downstream of PTENP1. Next, both in vitro and in vivo experiments were employed to explore the function. Cell proliferation was evaluated by CCK‐8, soft agar, and colony formation assays. Expression of relative genes was assessed by quantitative real‐time PCR (qRT‐PCR) and Western blotting. 3′UTR luciferase assay was used to confirm the miRNA binding. The clinical significance of PTENP1 was further validated by immunohistochemistry (IHC) and correlation with clinicopathological indicators in additional samples (n = 93). We found expression of PTENP1 in ESCC was lower than that in the corresponding adjacent normal tissues (n = 17). Overexpression of PTENP1 in Eca109 and TE‐1 cells resulted in inhibited proliferation and altered expression of SOCS6‐p‐STAT3‐HIF‐1α pathway both in vitro and in vivo. Subsequent IHC reported a similar trend in human ESCC samples. 3′UTR luciferase assay demonstrated that PTENP1 3′UTR decoyed miR‐17‐5p from binding to SOCS6. Moreover, PTENP1 expression was correlated with clinicopathological indicators to varying degrees, including histological grade, TNM stage, infiltration depth, lymph node metastasis, and overall survival. Taken together, these results suggested an anti‐oncogenic role of PTENP1. Meanwhile, PTENP1 may also serve as a candidate of prognostic indicator for ESCC patients.
“…Similar to these cardiac MHC isoforms, cardiac myosin light chain 2 (MLC-2v) is also transcribed during the course of differentiation [7]. When the 250 base pair (bp) promoter for the rat cardiac MLC-2v gene was connected upstream of the gene for green fluorescent protein (GFP) together with the enhancer portion of the cytomegalovirus (CMV) immediate early promoter, and the resulting reporter plasmid was stably introduced into P19CL6 cells, expression of GFP was limited to developing cardiac myocytes [8].…”
The P19CL6 mouse embryonic carcinoma cells efficiently differentiate into cardiac muscle cells in the presence of DMSO. A reporter plasmid for cardiac muscle differentiation was constructed by connecting the CMV enhancer and a 250 bp MLC-2v promoter in front of the GFP gene to further evaluate the role of the CMV enhancer. This plasmid (pCBVenh/MLC-2v pro /EGFP) was stably introduced into P19CL6 cells, and the transfectant differentiated into cardiomyocytes with DMSO. Upon DMSO addition, GFP was immediately transcribed (within 2 days) and the amount of the transcript increased with cultivation. Concomitantly, GFP fluorescence was detected in the cells under a microscope. However, native MLC-2v was transcribed later on day 4. This expression time course is different from that of GFP. Clearly the CMV enhancer responded immediately to DMSO. Since GATA DNA-binding proteins play crucial roles in the initiation of cardiomyocyte differentiation, such a response could be ascribed to the presence of multiple GATA motifs in the enhancer sequence but not in the native MLC-2v promoter. Thus the CMV enhancer may be not only useful for gene therapy and monitoring cell differentiation but also the study of the role of GATA transcription factors expressed in P19CL6 cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.