Xu Rujin, Ci Xingyuan, He Fang, Chen Yueqin
Laboratory Department, Hangzhou Linping First People's Hospital Hangzhou 311400, Zhejiang, P. R. China.
Am J Cancer Res. 2023 Jun 15;13(6):2360-2375. eCollection 2023.
Accumulating evidence has revealed that circular RNAs (circRNAs) play important roles in cancer by sponging microRNAs (miRNAs). A previous study has shown that hsa_circ_001350 expression is increased in glioma tissue samples and cells and that hsa_circ_001350 directly sponges miR-1236. Here, we investigated the role of hsa_circ_001350 in osteosarcoma (OS). Bioinformatics analysis was performed to examine the potential interactions among hsa_circ_001350, miR-578, and the CCR4-NOT transcription complex and subunit 7 (CNOT7). Reverse transcription-quantitative polymerase chain reaction and western blotting were performed to analyze gene expression and protein levels, respectively. Hsa_circ_001350 expression was upregulated in OS tissues and cell lines. The deletion of hsa_circ_001350 inhibited the proliferation, migration, and invasion of OS cells. The downregulation of hsa_circ_001350 suppressed CNOT7 expression by sponging miR-578 as confirmed by rescue experiments and luciferase reporter assays. Specifically, the depletion of hsa_circ_001350 inhibited the protein expression of β-catenin, cyclin D1, and c-myc in OS cells, and CNOT7 overexpression reversed this effect. We conclude that hsa_circ_001350 contributes to OS progression by regulating miR-578/CNOT7/Wnt signaling. Thus, hsa_circ_001350, miR-578, and CNOT7 may be potential targets for the treatment of OS.
越来越多的证据表明，环状RNA（circRNAs）通过充当微小RNA（miRNAs）的海绵在癌症中发挥重要作用。先前的一项研究表明，hsa_circ_001350在胶质瘤组织样本和细胞中的表达增加，且hsa_circ_001350直接充当miR-1236的海绵。在此，我们研究了hsa_circ_001350在骨肉瘤（OS）中的作用。进行生物信息学分析以检测hsa_circ_001350、miR-578和CCR4-NOT转录复合体及亚基7（CNOT7）之间的潜在相互作用。分别进行逆转录定量聚合酶链反应和蛋白质印迹分析基因表达和蛋白质水平。hsa_circ_001350在OS组织和细胞系中表达上调。缺失hsa_circ_001350可抑制OS细胞的增殖、迁移和侵袭。挽救实验和荧光素酶报告基因检测证实，hsa_circ_001350的下调通过充当miR-578的海绵抑制CNOT7表达。具体而言，缺失hsa_circ_001350可抑制OS细胞中β-连环蛋白、细胞周期蛋白D1和c-myc的蛋白质表达，而CNOT7过表达可逆转这一效应。我们得出结论，hsa_circ_001350通过调节miR-578/CNOT7/ Wnt信号通路促进OS进展。因此，hsa_circ_001350、miR-578和CNOT7可能是OS治疗的潜在靶点。
