Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.
J Cell Biochem. 2019 Mar;120(3):4092-4101. doi: 10.1002/jcb.27694. Epub 2018 Nov 28.
Emerging evidence suggests that long noncoding RNAs (lncRNAs) are involved in many biological processes, such as cell growth, differentiation, apoptosis, and autophagy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), highly expressed in endothelial cells, is well conserved and implicated in endothelial cell migration and proliferation. However, whether MALAT1 participates in oxidized low-density lipoprotein (ox-LDL)-induced autophagy regulation in human umbilical vein endothelial cells (HUVECs) remains unknown. In this study, we observed that autophagy was upregulated and MALAT1 expression was markedly increased in HUVECs treated with ox-LDL. The ox-LDL-induced autophagy of HUVECs is significantly associated with the PI3K/AKT pathway. Furthermore, we found that MALAT1 overexpression inhibited PI3K, Akt and p70S6K phosphorylation and downregulated RHEB expression, simultaneously increasing ox-LDL-induced autophagy. MALAT1 silencing caused higher phosphorylated PI3K, Akt and p70S6K levels, upregulated RHEB expression and markedly suppressed autophagy. These results indicated that lncRNA MALAT1 promotes ox-LDL-induced autophagy in HUVECs partly through the PI3K/AKT signaling pathway.
新出现的证据表明，长非编码 RNA（lncRNA）参与许多生物学过程，如细胞生长、分化、凋亡和自噬。在血管内皮细胞中高表达的转移相关肺腺癌转录本 1（MALAT1）高度保守，与内皮细胞迁移和增殖有关。然而，MALAT1 是否参与人脐静脉内皮细胞（HUVEC）中氧化低密度脂蛋白（ox-LDL）诱导的自噬调节尚不清楚。在这项研究中，我们观察到 ox-LDL 处理的 HUVEC 中自噬上调，MALAT1 表达明显增加。ox-LDL 诱导的 HUVEC 自噬与 PI3K/AKT 途径显著相关。此外，我们发现 MALAT1 过表达抑制了 PI3K、Akt 和 p70S6K 的磷酸化，下调了 RHEB 的表达，同时增加了 ox-LDL 诱导的自噬。MALAT1 沉默导致磷酸化的 PI3K、Akt 和 p70S6K 水平升高，上调了 RHEB 的表达，并显著抑制了自噬。这些结果表明，lncRNA MALAT1 通过 PI3K/AKT 信号通路促进 HUVEC 中 ox-LDL 诱导的自噬。
