MiR‐590‐3p regulates cardiomyocyte P19CL6 proliferation, apoptosis and differentiation in vitro by targeting PTPN1 via JNK/STAT/NF‐kB pathway

Abstract

Cardiomyocyte differentiation is a multi-step process which involves a number of signalling pathways. microRNAs exhibit regulatory functions in various diseases and are involved in the signalling pathways in multiple physiological processes, but the specific functions of particular mRNAs is often not fully understood. of an example of this is that the role of miR-590-3p in the differentiation of cardiomyocytes remains unclear. In the current study, RT-qPCR was used to determine the expression of miR-590-3p in cardiomyocytes differentiated from the embryonic carcinoma cell line P19CL6. MTT, EdU, caspase-3 activity and flow cytometry assays were performed to examine the influence of miR-590-3p on cell behaviour. A luciferase assay was used to confirm binding between miR-590-3p and PTPN1. Western blotting was used to determine the relationship between the JNK/STAT/NF-kB pathway and PTPN1. The results inferred that miR-590-3p became heavily expressed in differentiated P19CL6. Knockdown miR-590-3p suppressed the cell proliferation while at the same time, accelerated apoptosis. Moreover, PTPN1 was identified as the target of miR-590-3p. More importantly, PTPN1 overexpression activated the JNK/STAT/ NF-kB pathway and limited the differentiation of P19CL6. Thus the conclusions from this study are that miR-590-3p has the potential to regulate the proliferation, apoptosis and differentiation of cardiomyocyte P19CL6 in vitro by targeting PTPN1 via the JNK/STAT/NF-kB pathway.

Curcumin alters distinct molecular pathways in breast cancer subtypes revealed by integrated miRNA/mRNA expression analysis

“…miR‐590‐3p is known to regulate the proliferation, apoptosis by targeting PTPN1 via the JNK/STAT/NF‐kB pathway. 55 , 56 miR‐106a and let‐7 are also known to regulate the NF‐kB pathway, 57 , 58 confirming the previous observations in several cancer cell lines that curcumin exerts its effect via the inhibition of the NF‐kB pathway. To dissect the mechanism of NF‐KB inhibition induced by curcumin treatment, we further analyzed the NF‐kB pathway in all three cells upon curcumin treatment.…”

“…In MCF7 miR‐590‐3p, in MDA‐MB‐231 miR‐106a‐3p and in T47D let‐7c‐3p regulates maximum number of DE genes upon curcumin treatment. miR‐590‐3p is known to regulate the proliferation, apoptosis by targeting PTPN1 via the JNK/STAT/NF‐kB pathway 55,56 . miR‐106a and let‐7 are also known to regulate the NF‐kB pathway, 57,58 confirming the previous observations in several cancer cell lines that curcumin exerts its effect via the inhibition of the NF‐kB pathway.…”

Circ_0124644 Serves as a ceRNA for miR-590-3p to Promote Hypoxia-Induced Cardiomyocytes Injury via Regulating SOX4

“…In the past reports, miR-590-3p was confirmed to participate in cancer progression as a tumor suppressor, including hepatocellular carcinoma (Pu et al, 2020), breast cancer (Shan et al, 2020), and papillary thyroid carcinoma (Tong et al, 2019). Wang et al showed that miR-590-3p silencing inhibited cardiomyocytes proliferation and differentiation, while it accelerated apoptosis (Wang F. et al, 2020). More importantly, miR-590-3p was found to restore cell cycle process to promote cardiomyocytes proliferation, and thus alleviating AMI progression (Wang et al, 2018).…”

Adaptation of cardiomyogenesis to the generation and maturation of cardiomyocytes from human pluripotent stem cells

“…miR‐199 was shown to inhibit Cd151 and, in turn, up‐regulate the pro‐proliferative pathway previously inhibited by Cd151‐p38 axis 45 . Similarly, miR‐590 targets Protein Tyrosine Phosphatase Non‐Receptor Type 1 (PTPN1), which promotes proliferation of CM through JNK/STAT/NF‐kB axis 46 . On the other hand, studies identified the miRNA‐15 (miR‐15) family as a key antiproliferative player in cardiomyocyte cell cycle withdrawal 47 (Figure 2).…”

“…45 Similarly, miR-590 targets Protein Tyrosine Phosphatase Non-Receptor Type 1 (PTPN1), which promotes proliferation of CM through JNK/STAT/NF-kB axis. 46 On the other hand, studies identified the miRNA-15 (miR-15) family as a key antiproliferative player in cardiomyocyte cell cycle withdrawal 47 (Figure 2). Members of the miR-15 family (À15a, À15b, 16-a, À16b, À195, and À497) target genes related to the cell cycle (Chek1, Cdc2a, Birc5, Nusap1, and Spag5) and start to be expressed shortly after birth, reaching a peak around week 2 in mice, coinciding with the end of the transient proliferative window of CM after birth.…”