Circ-RNF121 regulates tumor progression and glucose metabolism by miR-1224-5p/FOXM1 axis in colorectal cancer.

Circ-RNF121 regulates tumor progression and glucose metabolism by miR-1224-5p/FOXM1 axis in colorectal cancer.
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DOI:
10.1186/s12935-021-02290-3
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发表时间:
2021-11-06
影响因子:
5.8
通讯作者:
Chen S
Chen S
中科院分区:
医学2区
文献类型:
--
作者:
Jiang Z;Hu H;Hu W;Hou Z;Liu W;Yu Z;Liang Z;Chen S

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先前的研究报道环状RNA (circRNA)与CRC的发病机制有关。本研究旨在揭示circ-无名指蛋白121 (circ-RNF121)在结直肠癌(CRC)中的作用机制。采用实时荧光定量聚合酶链式反应(qRT-PCR)检测circ-RNF121、microRNA-1224-5p (miR-1224-5p)和叉头盒M1 (FOXM1)水平。western blot检测蛋白水平。用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四唑(MTT)和细胞集落形成试验分析细胞增殖情况。流式细胞术检测细胞凋亡情况。用transwell法和创面愈合法观察细胞迁移和侵袭。采用葡萄糖、乳酸和ADP/ATP比值测定试剂盒检测细胞糖酵解。通过starBase在线数据库预测miR-1224-5p与circ-RNF121或FOXM1的结合关系,并通过双荧光素酶报告基因法鉴定。通过体内肿瘤形成实验揭示了circ-RNF121沉默对体内肿瘤形成的影响。与对照组相比,CRC组织或细胞中Circ-RNF121和FOXM1的表达显著上调,miR-1224-5p的表达下调。Circ-RNF121沉默抑制CRC细胞增殖、迁移、侵袭和糖酵解,但诱导细胞凋亡,miR-1224-5p抑制剂可减弱这些作用。此外,circ-RNF121作为miR-1224-5p和miR-1224-5p结合FOXM1的海绵。Circ-RNF121沉默在体内抑制肿瘤生长。此外,circ-RNF121通过被包装到外泌体中来分泌。这一发现为研究环状rna介导的结直肠癌治疗提供了新的见解。在线版本包含补充材料,可在10.1186/s12935-021-02290-3获得。
Previous studies have reported that circular RNA (circRNA) is associated with the pathogenesis of CRC. This study was designed to reveal the mechanism of circ-ring finger protein 121 (circ-RNF121) in colorectal cancer (CRC). The levels of circ-RNF121, microRNA-1224-5p (miR-1224-5p) and forkhead box M1 (FOXM1) were determined by quantitative real-time polymerase chain reaction (qRT-PCR). Protein level was detected by western blot. Cell proliferation was analyzed by 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell colony formation assays. Flow cytometry analysis was performed to investigate cell apoptosis. Cell migration and invasion were investigated by transwell and wound-healing assays. Cell glycolysis was detected using glucose, lactate and ADP/ATP ratio assay kits. The binding relationship between miR-1224-5p and circ-RNF121 or FOXM1 was predicted by starBase online database, and identified by dual-luciferase reporter assay. The impacts of circ-RNF121 silencing on tumor formation in vivo were disclosed by in vivo tumor formation assay. Circ-RNF121 and FOXM1 expression were dramatically upregulated, while miR-1224-5p expression was downregulated in CRC tissues or cells compared with control groups. Circ-RNF121 silencing repressed cell proliferation, migration, invasion and glycolysis but induced cell apoptosis in CRC, which were attenuated by miR-1224-5p inhibitor. Additionally, circ-RNF121 acted as a sponge of miR-1224-5p and miR-1224-5p bound to FOXM1. Circ-RNF121 silencing inhibited tumor growth in vivo. Furthermore, circ-RNF121 was secreted through being packaged into exosomes. The finding provided a novel insight into studying circRNA-mediated CRC therapy. The online version contains supplementary material available at 10.1186/s12935-021-02290-3.
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