Liu Fangyu, Wang Yulin, Huang Xitong, Liu Dingqian, Ding Wenjun, Lai Hao, Wang Chunsheng, Ji Qiang
Department of Cardiovascular Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shanghai Municipal Institute for Cardiovascular Diseases, Shanghai, 200032, China.
Cell Death Discov. 2023 Aug 18;9(1):301. doi: 10.1038/s41420-023-01601-z.
Long intergenic nonprotein coding RNA 2015 (LINC02015) is a long non-coding RNA that has been found elevated in various cell proliferation-related diseases. However, the functions and interactive mechanism of LINC02015 remain unknown. This study aimed to explore the role of LINC02015 in the cell proliferation and apoptosis of vascular smooth muscle cells (VSMCs) to explain the pathogenesis of aortic diseases. Ascending aorta samples and angiotensin-II (AT-II) treated primary human aortic VSMCs (HAVSMCs) were used to evaluate the LINC02015 expression. RNA sequencing, chromatin isolation by RNA purification sequencing, RNA pull-down, and mass spectrometry (MS) were applied to explore the potential interacting mechanisms. LINC02015 expression was found elevated in aortic dissection and AT-II-treated HAVSMCs. Cell proliferation and cell cycle were activated in HAVSMCs with LINC02015 knockdown. The cyclins family and caspase family were found to participate in regulating the cell cycle and apoptosis via the NF-κB signaling pathway. RXRA was discovered as a possible hub gene for LINC02015 transcriptional regulating networks. Besides, the protein interaction network of LINC02015 was revealed with candidate regulating molecules. It was concluded that the knockdown of LINC02015 could promote cell proliferation and inhibit the apoptosis of HAVSMCs through an RXRA-related transcriptional regulation network, which could provide a potential therapeutic target for aortic diseases.
长链基因间非编码RNA 2015(LINC02015)是一种长链非编码RNA,已发现在各种与细胞增殖相关的疾病中表达升高。然而,LINC02015的功能及其相互作用机制仍不清楚。本研究旨在探讨LINC02015在血管平滑肌细胞(VSMC)增殖和凋亡中的作用,以阐明主动脉疾病的发病机制。采用升主动脉样本和血管紧张素II(AT-II)处理的原代人主动脉VSMC(HAVSMC)来评估LINC02015的表达。应用RNA测序、RNA纯化测序染色质分离、RNA下拉和质谱(MS)来探索潜在的相互作用机制。发现LINC02015在主动脉夹层和AT-II处理的HAVSMC中表达升高。敲低LINC02015后,HAVSMC中的细胞增殖和细胞周期被激活。发现细胞周期蛋白家族和半胱天冬酶家族通过NF-κB信号通路参与调节细胞周期和凋亡。RXRA被发现是LINC02015转录调控网络的一个可能的枢纽基因。此外,还揭示了LINC02015与候选调控分子的蛋白质相互作用网络。得出的结论是,敲低LINC02015可通过与RXRA相关的转录调控网络促进HAVSMC的细胞增殖并抑制其凋亡,这可为主动脉疾病提供潜在的治疗靶点。