Jia Nan, Song Zhe, Chen Baosheng, Cheng Jinsheng, Zhou Wenyong
Department of General Surgery, CangZhou General Hospital, CangZhou, Hebei, 061001, People's Republic of China.
Onco Targets Ther. 2021 Apr 23;14:2829-2838. doi: 10.2147/OTT.S292320. eCollection 2021.
Aberrant circular RNA (circRNA) expression has been extensively discovered for its involvement in both the initiation and progression of various cancers. Through screening circRNA profile, we identified a novel circRNA has_circ_0001806, which is termed as circCSPP1 in liver cancer. In the present study, we aim to investigate the role of circCSPP1 in the progression of liver cancer.
Fluorescence in situ hybridization (FISH) was used to detect the location of circCSPP1. Function studies including MTT, colony formation assay, transwell assay and flow cytometry were carried out to detect the malignant behaviour of circCSPP1 on liver cancer cells. Luciferase assay and RNA pull down were used to detect the interaction between miR-1182 and circCSPP1 as well as RAB15. Quantitative realtime (qPCR) and Western blot were performed to evaluate the RNA and protein expression, respectively.
CircCSPP1 knockdown inhibited the proliferation, migration and invasion while promoted apoptosis of liver cancer cells. Mechanically, we predicted and verified the target miR of circCSPP1 which is miR-1182. miR-1182 was capable of reversing the effect of circCSPP1 on liver cancer cells. Moreover, miR-1182 was found to also target RAB15 to participate in the regulation of cell phenotype.
Taken together, circCSPP1 promoted progression of liver cancer cells via sponging miR-1182 which may serve as a novel prognostic and therapeutic target for liver cancer.
异常环状RNA(circRNA)的表达因其参与多种癌症的发生和发展而被广泛发现。通过筛选circRNA谱,我们鉴定出一种新型circRNA has_circ_0001806,在肝癌中它被命名为circCSPP1。在本研究中,我们旨在探讨circCSPP1在肝癌进展中的作用。
采用荧光原位杂交(FISH)检测circCSPP1的定位。进行包括MTT、集落形成试验、Transwell试验和流式细胞术在内的功能研究,以检测circCSPP1对肝癌细胞恶性行为的影响。采用荧光素酶报告基因试验和RNA下拉试验检测miR-1182与circCSPP1以及RAB15之间的相互作用。分别进行定量实时(qPCR)和蛋白质免疫印迹法以评估RNA和蛋白质表达。
circCSPP1敲低抑制了肝癌细胞的增殖、迁移和侵袭,同时促进了其凋亡。机制上,我们预测并验证了circCSPP1的靶标miR为miR-1182。miR-1182能够逆转circCSPP1对肝癌细胞的作用。此外,发现miR-1182也靶向RAB15参与细胞表型的调控。
综上所述,circCSPP1通过吸附miR-1182促进肝癌细胞进展,miR-1182可能成为肝癌新的预后和治疗靶点。