1. lncRNA 通過調控肌動蛋白結合蛋白NEXN緩解動脈粥樣硬化（IF13.251 J Clin Invest）
摘要: Noncoding RNAs are emerging as important players in gene regulation and disease pathogeneses. Here, we show that a previously uncharacterized long noncoding RNA, nexilin F-actin binding protein antisense RNA 1 (NEXN-AS1), modulates the expression of the actin-binding protein NEXN and that NEXN exerts a protective role against atherosclerosis. An expression
microarray analysis showed that the expression of both NEXN-AS1 and NEXN was reduced in human atherosclerotic plaques. In vitro experiments revealed that NEXN-AS1 interacted with the chromatin remodeler BAZ1A and the 5′ flanking region of the NEXN gene and that it also upregulated NEXN expression. Augmentation of NEXN-AS1 expression inhibited TLR4 oligomerization and NF-κB activity, downregulated the expression of adhesion molecules and inflammatory cytokines by endothelial cells, and suppressed monocyte adhesion to endothelial cells. These inhibitory effects of NEXN-AS1 were abolished by knockdown of NEXN. In vivo experiments using ApoE-knockout mice fed a Western high-fat diet demonstrated that NEXN deficiency promoted atherosclerosis and increased macrophage abundance in atherosclerotic lesions, with heightened expression of adhesion molecules and inflammatory cytokines, whereas augmented NEXN expression deterred atherosclerosis. Patients with coronary artery disease were found to have lower blood NEXN levels than healthy individuals. These results indicate that NEXN-AS1 and NEXN represent potential therapeutic targets in atherosclerosis-related diseases.
2. CircSERPINE2 通過作用于of miR-1271及EST相關基因預防骨關節炎（IF14.299 Ann Rheum Dis）
摘要:The decreased expression of CircSERPINE2 in the OA cartilage tissues was directly associated with excessive apoptosis and imbalance between anabolic and catabolic factors of extracellular matrix (ECM). Mechanistically, CircSERPINE2 acted as a sponge of miR-1271-5 p and functioned in human chondrocytes (HCs) through targeting miR-1271-5 p and ERG. Intra-articular
injection of adeno-associated virus-CircSERPINE2-wt alleviated OA in the rabbit model.
3.circPCMTD1對 miR-224-5p起分子海綿作用，促進神經膠細胞瘤形成 （IF4.137, Frontiers in Oncology）
摘要: Glioma is the most common malignant tumor of the central nervous system with high morbidity and mortality. Circular RNAs (circRNAs) are abundant non-coding RNAs, which contribute to tumor progression by competing with other endogenous RNAs such as microRNA (miRNA). MiRNA are a class of small non-coding RNAs, which interrupt the translation of target mRNAs. CircPCMTD1 (hsa-circ-0001801) is a newly discovered circRNA that was found to be significantly upregulated in glioma. However, its function is unclear. In this study, circPCMTD1 upregulation promoted the cell viability, migration and invasion dramatically, while the inhibition of circPCMTD1 led to a significant reduction of tumor growth in vivo. MiRNAs microarray analyses on circPCMTD1 silencing models in U251 and U118MG cells were performed, and the results suggested that circPCMTD1 knockdown could upregulate the expression of miR-224-5p and downregulate the expression of mTOR, one of miR-224-5p targets, in both cell lines. According to the prediction from circular RNA interactome and Targetscan, there was a complementary sequence in circPCMTD1 for miR-224-5p. Dual-luciferase reporter assay demonstrated that circPCMTD1 were targets of miR-224-5p. RIP assay was also performed to further confirm their directly interaction. Overexpression of miR-224-5p inhibited the viability and proliferation, migration, and invasion of U251 and U118MG glioma cells. In conclusion, circPCMTD1 could contribute to the promotion of glioma progression, and it may serve as the sponge of miR-224-5p to exert its function.