环状RNA circ_0007142通过miR-122-5p调控细胞周期蛋白磷酸酶25A（CDC25A）的表达促进结直肠癌进展。
Circular RNA circ_0007142 Facilitates Colorectal Cancer Progression by Modulating CDC25A Expression via miR-122-5p.
作者信息
Yin Wenzhe, Xu Jun, Li Chao, Dai Xiankui, Wu Tong, Wen Jifeng
机构信息
Department of Orthopaedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China.
Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, People's Republic of China.
出版信息
Onco Targets Ther. 2020 May 1;13:3689-3701. doi: 10.2147/OTT.S238338. eCollection 2020.
BACKGROUND
Colorectal cancer (CRC) is a common malignant tumor in digestive system. Circular RNA (circRNA) circ_0007142 has been identified as an oncogene in CRC. However, the mechanism of circ_0007142 in CRC was rarely reported.
MATERIALS AND METHODS
The levels of circ_0007142, dedicator of cytokinesis 1 (DOCK1), microRNA-122-5p (miR-122-5p), and cell division cycle 25A (CDC25A) in CRC tissues (n=31) and cells were examined by quantitative real-time polymerase chain reaction (qRT-PCR). The cell viability and colony-forming ability were evaluated via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay and colony-formation assay, respectively. The migrated and invaded abilities were monitored by Transwell assay. The dual-luciferase reporter assay was performed to validate the interactions between miR-122-5p and circ_0007142 or CDC25A. The protein level of CDC25A was detected via Western blot assay. The biological role of circ_0007142 was examined by xenograft tumor model in vivo.
RESULTS
The levels of circ_0007142 and CDC25A were enhanced and the level of miR-122-5p was declined in CRC tissues and cells, while the level of DOCK1 had no fluctuation. Circ_0007142 sponged miR-122-5p and CDC25A was a target of miR-122-5p. Circ_0007142 knockdown impeded cell proliferation, colony formation, migration, and invasion in CRC cells by regulating miR-122-5p. Besides, miR-122-5p inhibitor promoted cell proliferation, colony formation, migration, and invasion in CRC cells by modulating CDC25A. Circ_0007142 regulated CDC25A expression in CRC cells by sponging miR-122-5p. Moreover, circ_0007142 knockdown blocked CRC tumor growth in vivo.
CONCLUSION
Circ_0007142 modulated CDC25A expression to promote CRC progression by sponging miR-122-5p.
背景
结直肠癌（CRC）是消化系统常见的恶性肿瘤。环状RNA（circRNA）circ_0007142已被确定为结直肠癌中的一种癌基因。然而，circ_0007142在结直肠癌中的作用机制鲜有报道。
材料与方法
采用定量实时聚合酶链反应（qRT-PCR）检测31例结直肠癌组织及细胞中circ_0007142、细胞分裂周期蛋白1（DOCK1）、微小RNA-122-5p（miR-122-5p）和细胞分裂周期蛋白25A（CDC25A）的水平。分别通过3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四氮唑溴盐（MTT）法和集落形成试验评估细胞活力和集落形成能力。采用Transwell试验监测细胞迁移和侵袭能力。进行双荧光素酶报告基因试验以验证miR-122-5p与circ_0007142或CDC25A之间的相互作用。通过蛋白质免疫印迹法检测CDC25A的蛋白水平。通过体内异种移植肿瘤模型研究circ_0007142的生物学作用。
结果
结直肠癌组织和细胞中circ_0007142和CDC25A水平升高，miR-122-5p水平降低，而DOCK1水平无波动。Circ_0007142吸附miR-122-5p，且CDC25A是miR-122-5p的靶基因。敲低circ_0007142可通过调节miR-122-5p抑制结直肠癌细胞的增殖、集落形成、迁移和侵袭。此外，miR-122-5p抑制剂可通过调节CDC25A促进结直肠癌细胞的增殖、集落形成、迁移和侵袭。Circ_0007142通过吸附miR-122-5p调节结直肠癌细胞中CDC25A的表达。此外，敲低circ_0007142可抑制体内结直肠癌肿瘤生长。
结论
Circ_0007142通过吸附miR-122-5p调节CDC25A表达，促进结直肠癌进展。
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