miR‑144‑3p inhibits the proliferation, migration and angiogenesis of multiple myeloma cells by targeting myocyte enhancer factor 2A

Abstract

Multiple myelomas (MM) are the second most common haematological malignancy, for which no curative treatments have been reported to date. MicroRNAs (miRNAs or miRs) have recently been shown to be involved in the proliferation of MM cells. However, the molecular mechanisms through which miRNAs regulate migration and angiogenesis in MM are poorly understood. Accordingly, the present study evaluated the role of miR-144-3p in MM. miR-144-3p exhibited a lower expression in patients with MM and in MM cell lines compared with normal cells (mononuclear cells derived from bone marrow). The transfection of miR-144-3p into MM cells inhibited proliferation, migration and angiogenesis, and induced cell cycle arrest and apoptosis compared to the control cells. Furthermore, miR-144-3p suppressed the transcription and translation of the myocyte enhancer factor 2A (MEF2A) gene and disrupted the expression of vascular endothelial growth factor. The knockdown of MEF2A significantly inhibited the proliferation, migration and angiogenesis of MM cells. However, the overexpression of MEF2A reversed these effects. On the whole, the findings of the present study demonstrate that miR-144-3p exerts antitumour effects by downregulating MEF2A to inhibit the proliferation, migration and angiogenesis of MM cells. This suggests that the miR-144-3p /MEF2A interaction may prove to be a potential therapeutic target for MM.

TOP2A promotes proliferation and metastasis of hepatocellular carcinoma regulated by miR-144-3p

“…It is known to have effects on a variety of diseases and to regulate the production of proteins by interacting with mRNA 16 , 33 , 34 . Previous studies have shown that miR-144-3p can regulate the proliferation, migration, invasion and biological behaviors of various tumor cells that are drug resistant 35 - 37 . For example, miR-144-3p promotes the tumor growth and metastasis of papillary thyroid carcinoma by targeting paired box gene 8 38 .…”

Role of microRNAs in B-Cell Compartment: Development, Proliferation and Hematological Diseases

“…Multiple miRNAs are related to multiple myeloma. miR-144, downregulated in MM patients and MM cell lines, targets MEF2a (myocyte enhancer factor 2A) and inhibits the proliferation, migration and angiogenesis of MM cells and the overexpression reverses the effects [ 132 ]. The direct target of miR-144 is transmembrane tyrosine kinase c-MET, which is involved in invasion, migration, proliferation and angiogenesis [ 133 ].…”

Myocyte Enhancer Factor 2A Plays a Central Role in the Regulatory Networks of Cellular Physiopathology

“…Transforming growth factor (TGF)-β plays a role in the invasion, metastasis and growth of cancer cells by promoting HDAC degradation and histone hyper-acetylation at the MEF2 site of the matrix metalloproteinase (MMP-10) promoter, and by activating MEF2A and up-regulating the expression of MMP-10 [103]. MEF2A expression is thought to promote the progression of multiple myeloma [104] and of colorectal cancer [105], with higher expression correlating with poor prognosis. P38 MAPK activation in the gastric cancer cell line MKN45 up-regulates GLUT-4 in a MEF2Adependent manner and promotes glucose uptake and cell growth [106].…”

“…MiR-155 for example inhibits the expression of MEF2A, while the lncRNA malat1 up-regulates the expression of MEF2A by adsorbing miR-155, thus promoting cardiomyocyte proliferation [135]. miR-144-3P was shown to have antitumor properties by inhibiting the expression of MEF2A [104], while miR-194-5p delays the progression of sepsis by down-regulating MEF2A [136].…”