miR-543 and miR-590-3p regulate human mesenchymal stem cell aging via direct targeting of AIMP3/p18

Kim

et al. 2019

Cells

Self Cite

Human palatine tonsils are potential tissue source of multipotent mesenchymal stem cells (MSCs). The proliferation rate of palatine tonsil-derived MSCs (TMSCs) is far higher than that of bone marrow-derived MSCs (BMSCs) or adipose tissue-derived MSCs (ADSCs). In our previous study, we had found through DNA microarray analysis that tensin-3 (TNS3), a type of focal adhesion protein, was more highly expressed in TMSCs than in both BMSCs and ADSCs. Here, the role of TNS3 in TMSCs and its relationship with integrin were investigated. TNS3 expression was significantly elevated in TMSCs than in other cell types. Cell growth curves revealed a significant decrease in the proliferation and migration of TMSCs treated with siRNA for TNS3 (siTNS3). siTNS3 treatment upregulated p16 and p21 levels and downregulated SOX2 expression and focal adhesion kinase, protein kinase B, and c-Jun N-terminal kinase phosphorylation. siTNS3 transfection significantly reduced adipogenic differentiation of TMSCs and slightly decreased osteogenic and chondrogenic differentiation. Furthermore, TNS3 inhibition reduced active integrin beta-1 (ITGβ1) expression, while total ITGβ1 expression was not affected. Inhibition of ITGβ1 expression in TMSCs by siRNA showed similar results observed in TNS3 inhibition. Thus, TNS3 may play an important role in TMSC proliferation and differentiation by regulating active ITGβ1 expression.

“…Senescence-associated beta-galactosidase staining was conducted as previously described [11]. Briefly, TMSCs were seeded into 6-well plates and incubated to reach 70-80% confluency.…”

Section: Senescence-associated Beta-galactosidase Stainingmentioning

confidence: 99%

Tensin-3 Regulates Integrin-Mediated Proliferation and Differentiation of Tonsil-Derived Mesenchymal Stem Cells

Kim

et al. 2019

Cells

Self Cite

“…A recent research has showed that miR-543 functions as an oncogene in hepatocellular carcinoma by targeting PAQR3 [27]. In addition, miR-543 has also been found to decrease the tumor suppressor AIMP3 in human stem cell by targeting AIMP3/p18 [28]. However, the biological effect of miR-543 in prostate cancer and the correlation between miR-543 and RKIP have not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

MiR-543 Promotes Proliferation and Epithelial-Mesenchymal Transition in Prostate Cancer via Targeting RKIP

Liu

Zhu

et al. 2017

Cell Physiol Biochem

Background/Aims: MicroRNAs (miRNAs, miRs) have emerged as important post-transcriptional regulators in various cancers. miR-543 has been reported to play critical roles in hepatocellular carcinoma and colorectal cancer, however, the role of miR-543 in the pathogenesis of prostate cancer has not been fully understood. Methods: Expression of miR-543 and Raf Kinase Inhibitory Protein (RKIP) in clinical prostate cancer specimens, two prostate cancer cell lines, namely LNCAP and C4-2B, were determined. The effects of miR-543 on proliferation and metastasis of tumor cells were also investigated with both in vitro and in vivo studies. Results: miR-543 was found to be negatively correlated with RKIP expression in clinical tumor samples and was significantly upregulated in metastatic prostate cancer cell line C4-2B compared with parental LNCAP cells. Further studies identified RKIP as a direct target of miR-543. Overexpression of miR-543 downregulated RKIP expression and promoted the proliferation and metastasis of cancer cells, whereas knockdown of miR-543 increased expression of RKIP and suppressed the proliferation and metastasis of cancer cells in vitro and in vivo. Conclusion: Our study demonstrates that miR-543 promotes the proliferation and metastasis of prostate cancer via targeting RKIP.

“…They also mediate several crucial signaling pathways in inflammation and carcinogenesis [8,10,11]. The role of NF-κB-related miRNA has been established in cancer, stem cells and lipid accumulation, but not in inflammation [12,13,14,15]. …”

Section: Introductionmentioning

confidence: 99%

miR-590-3p Is a Novel MicroRNA in Myocarditis by Targeting Nuclear Factor Kappa-B in vivo

et al. 2015

Objective: Nuclear factor kappa-B (NF-κB)-induced inflammation leads to myocarditis and heart dysfunction. How microRNAs (miRNAs) contribute to this process is poorly defined. The aim of this study was to investigate whether miRNAs regulate NF-κB-induced inflammation in experimental autoimmune myocarditis (EAM) in vivo. Methods and Results: NF-κB and its related proinflammatory genes, including interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), were activated in EAM. Profiling of NF-κB-related miRNAs revealed that miR-590-3p was strikingly reduced in EAM. We found IL-6-induced proinflammatory signaling via miR-590-3p reduction, p50 induction, NF-κB activation and IL-6/TNF-a expression. Moreover, a luciferase reporter assay demonstrated that miR-590-3p directly interacted with the 3' UTR (untranslated region) of the p50 subunit, and that miR-590-3p overexpression inhibited p50 expression. Finally, miR-590-3p transfection through adeno-associated virus significantly inhibited p50 expression, suppressed NF-κB activity and blocked IL-6/TNF-a expression in vivo, reducing the lesion area and improving cardiac function in EAM. Conclusion: miR-590-3p is a novel NF-κB-related miRNA that directly targets the p50 subunit. This may provide a novel strategy for the treatment of myocarditis.