Background::Non-coding RNAs have attracted considerable attention for their vital role in cancer. The purpose of this study was to determine the effects of non-coding RNAs on hepatocellular carcinoma (HCC) and reveal their regulatory mechanism in the pathophysiological process.Methods::We measured the expression of mucin 1 (MUC1) and miR-485-5p in tissues from 15 HCC patients and in liver cancer cell lines by quantitative real-time polymerase chain reaction and Western blot, screened for aberrantly expressed microRNAs (miRNAs) by miRNA microarrays. Bioinformatics tools were used to find the miRNA and circular RNA that regulated MUC1, which were validated by RNA immunoprecipitation assay and luciferase reporter assay. Cell counting kit-8, Transwell assays, and flow cytometry were used to conduct functional experiments. Proteins were examined by western blot and immunohistochemical staining assays. Significant differences between groups were estimated using the one-way analysis of variance. A P < 0.05 was considered statistically significant. Results::MUC1 was overexpressed in HCC tissues compared with that in paratumor tissues (normal vs. tumor, 1.007 ± 0.215 vs. 75.213 ± 18.403, t = 18.401, P < 0.001) while miR-485-5p was down-regulated (normal vs. tumor, 4.894 ± 0.684 vs. 1.586 ± 0.398, t= 16.191, P < 0.001). Inhibition of miR-485-5p promoted cell proliferation (73.33% ± 5.13% vs. 41.33% ± 3.51%, t= 8.913, P < 0.001), migration (102 ± 8 cells vs. 46 ± 8 cells, t= 8.681, P < 0.001), invasion (59 ± 7 cells vs. 28 ± 2 cells, t = 8.034, P < 0.01), and suppressed apoptosis (22.64% ± 6.97% vs. 36.33% ± 3.96%, t = 2.958, P < 0.05) of HepG2 cells with which MUC1 is knocked down. Mechanically, miR-485-5p binds to MUC1, while circHECTD1 binds to miR-485-5p, resulting in the indirect up-regulation of the MUC1 level. Conclusions::Our findings reveal that circHECTD1 facilitates HCC progression by sponging miR-485-5p to up-regulate MUC1.

巨噬细胞按表型和分泌的细胞因子主要分为两种不同的极化类型,即发挥"促炎和杀伤"作用的M1型极化和主导"抗炎和修复"功能的M2型极化.越来越多的研究发现,非编码RNA可靶向调控巨噬细胞极化通路中的关键蛋白而影响巨噬细胞极化状态,介导多种疾病的发生发展.非编码RNA(miRNA、lncRNA和circRNA)在调控巨噬细胞极化中发挥重要作用.其中,促进M1型巨噬细胞极化的miRNA主要有miR-27a、miR-223及let-7d-3p,促进M2型巨噬细胞极化的miRNA主要有miR-181、miR-93、miR-1246及miR-26a.lncRNA E330013P06、TCONS_00019715及基因间转录超保守RNA uc.306在M1巨噬细胞中高表达,lncRNA KCNQ1OT1、lncRNA Mirt2、lncRNA GAS5、、lncRNA cox-2及lncRNA MALAT1主要影响M2型巨噬细胞极化.circHECTD1、circZC3H4 RNA及mcircRas-GEF1B亦可调节M1/M2平衡,是肿瘤研究的热点.

背景:缺血性脑卒中是一种破坏性的脑血管疾病,与全球高致残率和死亡率有关.目前临床治疗缺血性脑卒中的效果有限,仍需进一步探究其发病机制,有助于寻求更新颖的治疗靶点.新近研究表明环状RNA不仅在基因表达调控中担当重要角色,而且在脑缺血发病机制中也发挥了重要作用.目的:从细胞凋亡、自噬、氧化应激、炎症反应、血管新生、血脑屏障等方面对环状RNA在脑缺血发病机制中的调控作用进行阐述,以期为临床研究提供思路.方法:应用计算机从中国知网(CNKI)、万方中文数据库及PubMed数据库检索2010年3月至2022年3月收录的相关文献;以"缺血性脑卒中、急性缺血性脑卒中、核糖核酸、非编码RNA、环状RNA、细胞凋亡、细胞自噬、氧化应激、炎症反应、血管新生、血脑屏障"为中文检索词,以"ischemic stroke,acute ischemic stroke,RNA,ncRNA,RNA,Circular,circRNA,apoptosis,autophagy,oxidative stress,inflammation,angiogenesis,blood brain barrier"为英文检索词,最终纳入48篇文献进行研究分析.结果 与结论:①环状RNA是一类具有闭合环状结构的非编码RNA分子,特点是反向剪接和缺乏5'端帽子和3'端多聚腺苷酸尾巴,其广泛存在于真核细胞中,具有许多重要的调控功能.已有证据表明环状RNA在缺血性脑卒中的病程发展中起着非常重要的作用,如:circSHOC2作为miR-7670-3p的海绵,可通过调节自噬促进去乙酰化酶1(SIRT1)的表达以减少神经元损伤;一项微阵列显示,当小鼠脑中动脉阻塞时circHECTD1的水平显著增加,敲低circHECTD1的表达可显著减少小鼠的脑梗死体积,进而减少其神经元损伤和改善星形胶质细胞激活.②环状RNA具有高度稳定性和进化保守性,其环状结构对核糖核酸酶不敏感,比线性更稳定,因此环状RNA可能在开发新型疾病诊断与治疗方法方面更具有潜力.③目前对于环状RNA在缺血性脑卒中的作用机制仅有少量研究,其具体机制仍不明朗,相关治疗策略也需进一步完善,因此深入研究环状RNA调控缺血性脑卒中后的作用机制,探索未来精准治疗缺血性脑卒中新的潜在靶点极其重要.