Long-Chain Non-Coding RNA Metastasis-Related Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes the Proliferation and Migration of Human Pulmonary Artery Smooth Muscle Cells (hPASMCs) by Regulating the MicroRNA-503 (miR-503)/Toll-Like Receptor 4 (TLR4) Signal Axis
Long-Chain Non-Coding RNA Metastasis-Related Lung Adenocarcinoma Transcript 1 (MALAT1) Promotes the Proliferation and Migration of Human Pulmonary Artery Smooth Muscle Cells (hPASMCs) by Regulating the MicroRNA-503 (miR-503)/Toll-Like Receptor 4 (TLR4) Signal Axis
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DOI：
10.12659/msm.923123
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发表时间：
2020-07-13
影响因子：
3.1
通讯作者：
Tao, Kelong
中科院分区：
文献类型：
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作者：
He, Meng;Shen, Juxin;Tao, Kelong
背景资料：探讨肺腺癌转移相关的长链非编码RNA（lncRNA）转录本1（MALAT 1）、microRNA-503（miR-503）、Toll样受体4（TLR 4）信号轴在肺动脉高压（PAH）发病中的作用。从45名PAH患者和45名健康受试者的血浆中提取总RNA，采用实时定量聚合酶链反应（qRT-PCR）检测lncRNA MALAT 1和miR-503的表达。体外转染人肺动脉平滑肌细胞（human pulmonary artery smooth muscle cells，hPASMCs），观察lncRNA MALAT 1和miR-503对TLR 4表达的影响，以及对hPASMCs增殖、迁移和凋亡的影响。沉默lncRNAMALAT 1抑制hPASMC细胞的增殖和迁移，同时促进其凋亡。miR-503在PAH患者的血浆和hPASMC中表达不足。TLR 4是miR-503的靶基因，在PAH患者外周血单个核细胞（PBMCs）中高表达。lncRNA MALAT 1是miR-503的“分子海绵”，通过miR-503调控TLR 4的表达，进而调控hPASMCs的增殖、迁移和凋亡。结论：lncRNA MALAT 1通过抑制miR-503/TLR 4信号轴，促进hPASMCs的增殖、迁移，抑制其凋亡。
Background: To study the role of the long-chain noncoding RNA (lncRNA) metastasis-related lung adenocarcinoma transcript 1 (MALAT1), microRNA-503 (miR-503), Toll-like receptor 4 (TLR4) signal axis in the pathogenesis of pulmonary arterial hypertension (PAH).Material/Methods: Total RNA was extracted from the plasma of 45 PAH patients and 45 healthy subjects, and the expression of lncRNA MALAT1 and miR-503 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of lncRNA MALAT1 and miR-503 on Toll-like receptor 4 (TLR4) and the proliferation, migration, and apoptosis of human pulmonary artery smooth muscle cells (hPASMCs) were tested following in vitro transfection of hPASMCs.Results: lncRNA MALAT1 was highly expressed in the plasma of PAH patients and in hypoxia-induced hPASMCs. Silencing lncRNA MALAT1 inhibited the proliferation and migration of hPASMC cells while promoting their apoptosis. MiR-503 is underexpressed in plasma and hPASMCs of patients with PAH. TLR4 was a target gene of miR-503 and was highly expressed in peripheral blood mononuclear cells (PBMCs) of PAH patients. lncRNA MALAT1 was a "molecular sponge" of miR-503, regulating the expression of TLR4 and the proliferation, migration, and apoptosis of hPASMCs through miR-503.Conclusions: lncRNA MALAT1 promotes the proliferation and migration of hPASMCs and inhibits their apoptosis by inhibiting the miR-503/TLR4 signal axis.