Xu Pei, Ding Yixin, Mo Bing, Wang Lei, Hu Fengqing, Yang Qi, Jiang Lianyong, Xiao Haibo, Ding Fangbao
Department of Cardiothoracic Surgery, Xinhua Hospital Affiliated to, Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, PR China.
Alberta Institute, Wenzhou Medical University, Wenzhou 325035, PR China.
Int Immunopharmacol. 2025 Jul 14;163:115137. doi: 10.1016/j.intimp.2025.115137.
Accumulation studies confirmed that circRNA play an important role in regulation the progress of non-small cell lung cancer (NSCLC). But the role of circRNA still largely unclear. So, the aim of this study was to explore new circRNA and underlying mechanisms through which they regulate NSCLC progression.
High-throughput sequencing were used to reveal the different expression of circRNA among NSCLC tissues and para-carcinoma tissue. Fluorescence in situ hybridization (FISH) were used to analysis the expression and subcellular localization of hsa_circ_0000571 in both NSCLC tissues and cells line. The regulatory mechanism and targets were then investigated utilizing bioinformatics analyses, luciferase reporter assay, transwell migration, clone formation experiment, CCK8, and EdU analysis. The in vivo experiments was used to elucidate the roles of hsa_circ_0000571 in NSCLC tumor metastasis and growth.
The study found that hsa_circ_0000571 expression was increased in both NSCLC tissues and cell lines, which indicated that hsa_circ_0000571 functions in NSCLC progression. FISH detection also show that hsa_circ_0000571 mainly located in the cytoplasm. And high expression of hsa_circ_0000571 was positively correlated with high tumor grade. Hsa_circ_0000571 downregulation inhibited NSCLC invasion and proliferation in both in vitro as well as in vivo experiments. Luciferase reporter data validated that both miR-654-5p and S100A11 were hsa_circ_0000571 downstream targets. S100A11 overexpression or miR-654-5p inhibition restored NSCLC cell proliferation and invasion post hsa_circ_0000571 silencing. Overexpression S100A11 restored NSCLC cell proliferation and invasion after overexpression miR-654-5p.
Downregulation of hsa_circ_0000571 suppressed NSCLC progression by miR-654-5p/S100A11 axis regulation.
积累研究证实环状RNA在调节非小细胞肺癌（NSCLC）进展中起重要作用。但环状RNA的作用仍很大程度上不清楚。因此，本研究的目的是探索新的环状RNA及其调节NSCLC进展的潜在机制。
采用高通量测序揭示NSCLC组织和癌旁组织中环状RNA的差异表达。荧光原位杂交（FISH）用于分析hsa_circ_0000571在NSCLC组织和细胞系中的表达及亚细胞定位。然后利用生物信息学分析、荧光素酶报告基因检测、Transwell迁移、克隆形成实验、CCK8和EdU分析研究其调控机制和靶点。体内实验用于阐明hsa_circ_0000571在NSCLC肿瘤转移和生长中的作用。
研究发现hsa_circ_0000571在NSCLC组织和细胞系中表达均增加，这表明hsa_circ_0000571在NSCLC进展中起作用。FISH检测还显示hsa_circ_0000571主要位于细胞质中。hsa_circ_0000571的高表达与高肿瘤分级呈正相关。在体外和体内实验中，hsa_circ_0000571下调均抑制NSCLC的侵袭和增殖。荧光素酶报告基因数据证实miR-654-5p和S100A11均为hsa_circ_0000571的下游靶点。S100A11过表达或miR-654-5p抑制可恢复hsa_circ_0000571沉默后NSCLC细胞的增殖和侵袭。miR-654-5p过表达后，S100A11过表达可恢复NSCLC细胞的增殖和侵袭。
hsa_circ_0000571的下调通过miR-654-5p/S100A11轴调节抑制NSCLC进展。
