MicroRNA-590 is an EMT-suppressive microRNA involved in the TGFβ signaling pathway

Abstract

Over the last few decades, the epithelial-to-mesenchymal transition (EMT) has been identified as being involved in a number of aspects of physiological processes and various pathological events, including embryonic development and renal fibrosis. Transforming growth factor-β receptor 2 (TGFβR2) is a widely studied gene, which fulfils a vital role in the TGFβ signaling pathway and exerts a crucial function in the progression of EMT. Previous studies demonstrated that the dysregulation of microRNAs (miRNAs) is considered to be associated with the EMT process. However, the precise functional involvement of miRNAs in EMT remains to be fully elucidated. In the present study, the level of miR-590 was decreased in an EMT model in vitro and in vivo. Furthermore, the overexpression of miR-590 inhibited EMT by upregulating the epithelial marker, E-cadherin, and downregulating the mesenchymal markers, laminin, α-smooth muscle actin (α-SMA) and collagen, in the human kidney 2 (HK2) cell line. Furthermore, TGFβR2 was negatively regulated by miR-590. In addition, performing a knockdown of TGFβR2 with small-interfering RNA had an effect similar to miR-590 on EMT in the HK2 cell line, whereas the transfection of pCMV-tag2B-TGFβR2 reversed the effect of miR-590 on EMT in HK2 cells. Taken together, the present study demonstrated that miR-590 is a novel EMT-suppressive microRNA, which targets TGFβR2.

MiR‐590 Promotes Transdifferentiation of Porcine and Human Fibroblasts Toward a Cardiomyocyte‐Like Fate by Directly Repressing Specificity Protein 1

“…Whereas the resistance of higher‐order cells to reprogramming is not well understood, it is thought to be related to the relative stability of the epigenetic signature of these cells . In this regard, the capability of miR‐590 to enhance cardiomyocyte transdifferentiation is consistent with its previously demonstrated ability to suppress the profibrotic TGFβ signaling pathway, as well as alpha‐smooth muscle actin and COL1 expression associated with myofibroblast generation . These observations are, in turn, reminiscent of the findings of Muraoka et al, who reported that addition of miR‐133 to GMT promotes cardiac reprogramming by directly inhibiting Snail 1 and silencing a fibroblast signature .…”

“…10 In this regard, the capability of miR-590 to enhance cardiomyocyte transdifferentiation is consistent with its previously demonstrated ability to suppress the profibrotic TGFb signaling pathway, as well as alpha-smooth muscle actin and COL1 expression associated with myofibroblast generation. 35,36 These observations are, in turn, reminiscent of the findings of Muraoka et al, who reported that addition of miR-133 to GMT promotes cardiac reprogramming by directly inhibiting Snail 1 and silencing a fibroblast signature. 26 The procardiomyocyte differentiating properties of miR-590 are likewise consistent with its role in suppressing epithelial-to mesenchymal transition, which has been identified as a morphogenic pathway leading differentiated cells toward a profibrotic state.…”

Retracted: MicroRNA‐300 promotes apoptosis and inhibits proliferation, migration, invasion and epithelial‐mesenchymal transition via the Wnt/β‐catenin signaling pathway by targeting CUL4B in pancreatic cancer cells

“…The miR-200 family members act as EMT inhibitors by targeting the transcription factor zine finger E-box binding homeobox 1 and 2. 15,21 Yu et al further provided evidence that downregulation of miR-300 is required for EMT initiation and maintenance, and MiR-300 may negatively regulate EMT by direct targeting Twist and therefore inhibit cancer cell invasion and metastasis. 15 EMT includes a series of epithelial plasticity changes in the epithelial and mesenchymal states.…”

Unveiling the role of microRNA‐7 in linking TGF‐β‐Smad‐mediated epithelial‐mesenchymal transition with negative regulation of trophoblast invasion

“…For instance, miR‐187 inactivates TGF‐β–induced EMT by directly suppressing the expression of SRY‐box 4, 5′‐nucleotidase ecto, and protein tyrosine kinase 6, the upstream effectors of Smad (49). Overexpression of miR‐590 also inhibits EMT by targeting type II TGF‐β receptor (TβRII) in the human kidney cell line (50). We hypothesized that TGF‐β negatively regulates the EMT of trophoblasts by fine‐tuning the expression of miRs.…”