Wu Ziheng, He Yangyan, Li Donglin, Fang Xin, Shang Tao, Zhang Hongkun, Zheng Xiangtao
Department of Vascular Surgery, The First Affiliated Hospital, School of Medicine, Zhejiang UniversityHangzhou 310000, Zhejiang, People's Republic of China.
Department of Vascular Surgery, Hangzhou First People's HospitalHangzhou 310000, People's Republic of China.
Am J Transl Res. 2017 Jul 15;9(7):3326-3335. eCollection 2017.
Long non-coding RNAs (lncRNAs) act critical roles in many biological processes, including cell proliferation, apoptosis, development, invasion and migration. LncRNA maternally expressed gene 3 (MEG3) is found to be downregulated in several tumors; however, its role in the atherosclerosis is still unknown. In the present study, we demonstrated that MEG3 expression level was downregulated in the coronary artery disease (CAD) tissues compared to in the control tissues. We also showed that TNF-α enhanced EC cell proliferation. In addition, the expression of MEG3 was increased in EC after treated with TNF-α. Overexpression of MEG3 suppressed EC cell proliferation and inhibited the expression of cyclin D1, ki-67 and PCNA. Elevated expression of MEG3 suppressed the type I collagen, type V collagen and proteoglycan expression. In addition, we showed that elevated expression of MEG3 suppressed the miR-21 expression in the EC and promoted the expression of RhoB and PTEN, which were the direct target genes of miR-21. We demonstrated that miR-21 expression level was upregulated in the CAD tissues compared to in the control tissues. Moreover, miR-21 expression was reversely correlated with MEG3 expression in the CAD tissues. Overexpression of MEG3 suppressed EC cell proliferation and type I collagen, type V collagen and proteoglycan expression through inhibiting miR-21 expression. These results suggested that MEG3 played a critical role in regulating EC proliferation and type I collagen, type V collagen and proteoglycan expression partly through suppressing miR-21 expression.
长链非编码RNA（lncRNAs）在许多生物学过程中发挥着关键作用，包括细胞增殖、凋亡、发育、侵袭和迁移。长链非编码RNA母系表达基因3（MEG3）在多种肿瘤中被发现表达下调；然而，其在动脉粥样硬化中的作用仍不清楚。在本研究中，我们证明与对照组织相比，冠状动脉疾病（CAD）组织中MEG3的表达水平下调。我们还表明肿瘤坏死因子-α（TNF-α）可促进内皮细胞（EC）增殖。此外，用TNF-α处理后，EC中MEG3的表达增加。MEG3过表达抑制EC细胞增殖，并抑制细胞周期蛋白D1、Ki-67和增殖细胞核抗原（PCNA）的表达。MEG3表达升高抑制I型胶原蛋白、V型胶原蛋白和蛋白聚糖的表达。此外，我们发现MEG3表达升高可抑制EC中miR-21的表达，并促进RhoB和PTEN的表达，而这两个基因是miR-21的直接靶基因。我们证明与对照组织相比，CAD组织中miR-21的表达水平上调。此外，CAD组织中miR-21的表达与MEG3的表达呈负相关。MEG3过表达通过抑制miR-21的表达来抑制EC细胞增殖以及I型胶原蛋白、V型胶原蛋白和蛋白聚糖的表达。这些结果表明，MEG3在调节EC增殖以及I型胶原蛋白、V型胶原蛋白和蛋白聚糖表达中发挥关键作用，部分是通过抑制miR-21的表达来实现的。
