Department of Cardiology, Huaihe Hospital, Henan University, Kaifeng, 475000, China.
Hum Cell. 2020 Jul;33(3):537-544. doi: 10.1007/s13577-020-00366-2. Epub 2020 May 24.
Previous studies have shown that some specific long non-coding RNAs are dysregulated in vascular walls and abnormally expressed in vascular disease. LncRNA HLA complex group 18 (HCG18) is a member of the HLA complex group, which has been rarely investigated in human diseases. In this study, we aimed to investigate the role of HCG in vascular smooth muscle cells. HCG18 was over-expressed by adenovirus transfection and knocked down in vascular smooth muscle cells by shRNA. Cell proliferation was detected by CCK-8 assays. Flow cytometry was employed to test the impacts of HCG18 on vascular smooth muscle apoptotic cells. The expression of associated genes in protein and mRNA levels was detected by western blotting, immunofluorescence and qRT-PCR. The interactions between HCG18 and fused in sarcoma (FUS) were confirmed by RNA EMSA and RIP assays. The expression of serum HCG18 was decreased in hypertensive patients and PDGF-BB-treated vascular smooth muscle cells. HCG18 inhibited proliferation and induced apoptotic cells in vascular smooth muscle cells. In addition, we also found that HCG18 can inhibit vascular smooth muscle cell phenotypic switching from a contractile to a secretory phenotype. Finally, our results showed that HCG18 enhanced apoptotic cells by directly binding with FUS. Our findings reveal that HCG18 is involved in the regulation of proliferation, apoptosis and the expression levels of markers of the contractile and synthetic phenotype.
先前的研究表明,一些特定的长非编码 RNA 在血管壁中失调,并在血管疾病中异常表达。长非编码 RNA HLA 复合体组 18(HCG18)是 HLA 复合体组的成员,在人类疾病中很少被研究。在本研究中,我们旨在研究 HCG 在血管平滑肌细胞中的作用。通过腺病毒转染过表达 HCG18,通过 shRNA 敲低血管平滑肌细胞中的 HCG18。通过 CCK-8 测定检测细胞增殖。通过流式细胞术检测 HCG18 对血管平滑肌细胞凋亡的影响。通过 Western blot、免疫荧光和 qRT-PCR 检测相关基因在蛋白和 mRNA 水平的表达。通过 RNA EMSA 和 RIP 测定证实 HCG18 与融合肉瘤(FUS)之间的相互作用。在高血压患者和 PDGF-BB 处理的血管平滑肌细胞中,血清 HCG18 的表达降低。HCG18 抑制血管平滑肌细胞的增殖并诱导凋亡细胞。此外,我们还发现 HCG18 可以抑制血管平滑肌细胞从收缩型向分泌型的表型转换。最后,我们的结果表明 HCG18 通过直接与 FUS 结合增强凋亡细胞。我们的研究结果表明,HCG18 参与调节增殖、凋亡以及收缩型和合成型表型标志物的表达水平。