Long non-coding RNA metastasis associated lung adenocarcinoma transcript 1(MALAT1) promotes hypertension by modulating the hsa-mir-124-3p/nuclear receptor subfamily 3, group C, member 2 (NR3C2) and Hsa-miR-135a-5p/NR3C2 axis

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Abstract

Background: This study was designed to investigate the role of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in the proliferation as well as apoptosis of human umbilical vein endothelial cells (HUVECs), to offer a basis for therapy of hypertension. Material/Methods: The lncRNA MALAT1 expression, hsa-miR-124-3p, hsa-miR-135a-5p, hsa-miR-135b-5p, and hsa-miR-455-5p in plasma were measured from 230 patients with hypertension and 230 non-hypertensive controls. The mechanism for lncRNA MALAT1 modulating the proliferation and apoptosis of HUVECs was explored by cell transfection, Cell Counting Kit-8 (CCK-8), quantitative real-time polymerase chain reaction (qRT-PCR), western blot, and dual-luciferase reporter assays. Results: The expression of hsa-miR-124-3p and hsa-miR-135a-5p was reduced and the expression of lncRNA MALAT1 was increased in the plasma of hypertensive patients. Moreover, the plasma levels of hsa-miR-124-3p and hsa-miR-135a-5p of hypertensive patients were negatively correlated with lncRNA MALAT1 (r=-0.64, -0.72; P<0.01, P<0.01, respectively). The level of nuclear receptor subfamily 3, group C, member 2 (NR3C2) protein was negatively correlated with hsa-miR-124-3p and hsa-miR-135a-5p (r=-0.74, -0.84; P<0.01, P<0.01, respectively). The proliferation of HUVECs was inhibited after the inhibition of MALAT. Additionally, after knocking down MALAT, the levels of hsa-miR-124-3p and hsa-miR-135a-5p in HUVECs were markedly increased, while the expression level of NR3C2 protein was decreased. The apoptotic rate of HUVECs after the transfection of MALAT1 small interfering RNA (si-MALAT1) (3.64±0.21%) was significantly reduced compared to that of transfected si-MALAT1 no template control (NC) (3.76±0.19%) and the control group (10.51±1.24%). Conclusions: LncRNA MALAT1 regulates proliferation and apoptosis of HUVECs through the hsa-miR-124-3p/NR3C2 and/or hsa-miR-135a-5p/NR3C2 axis.

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Luo, L., Wang, Y., Hu, P., & Wu, J. (2020). Long non-coding RNA metastasis associated lung adenocarcinoma transcript 1(MALAT1) promotes hypertension by modulating the hsa-mir-124-3p/nuclear receptor subfamily 3, group C, member 2 (NR3C2) and Hsa-miR-135a-5p/NR3C2 axis. Medical Science Monitor, 26. https://doi.org/10.12659/MSM.920478

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