Lin Zenghai, Lin Jianwei
Department of General Surgery, Guangdong Province, The First Affiliated Hospital of Shantou University Medical College, No. 57 Changping Road, Shantou City, 515041 Guangdong China.
Cell Mol Bioeng. 2023 Jan 20;16(2):159-171. doi: 10.1007/s12195-022-00756-6. eCollection 2023 Apr.
Colorectal cancer (CRC) is a common malignant tumor in the digestive tract. Circular RNAs (circRNAs) have been identified as crucial regulators of tumorigenesis. However, the role and potential mechanism of circ_0004585 in CRC are poorly understood.
The expression of circ_0004585, microRNA-338-3p (miR-338-3p), and zinc finger protein X-linked (ZFX) was detected by quantitative real-time PCR and Western blot. Cell proliferation, cell cycle arrest, apoptosis, and angiogenesis were evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT), 5-Ethynyl-2'-deoxyuridine (EdU), flow cytometry and tube formation assays. Western blot assay was applied to detect the expression of epithelial-mesenchymal transition (EMT)-related proteins and MEK/ERK signaling pathway-related proteins. A xenograft model was used to analyze tumor growth . The targeted relationship between miR-338-3p and circ_0004585/ZFX was verified by a dual-luciferase reporter assay.
Circ_0004585 and ZFX were up-regulated, while miR-338-3p was down-regulated in CRC tissues and cells. Silencing of circ_0004585 inhibited proliferation, angiogenesis, and EMT and triggered apoptosis in CRC cells. Consistently, circ_0004585 depletion blocked tumor growth . Circ_0004585 contributed to CRC cell development sequestering miR-338-3p. Also, miR-338-3p hindered the malignant progression of CRC cells by targeting ZFX. Circ_0004585 activated MEK/ERK pathway regulating ZFX.
Circ_0004585 facilitated CRC progression through modulating miR-338-3p/ZFX/MEK/ERK pathway, which might provide a potential therapeutic target for CRC.
The online version contains supplementary material available at 10.1007/s12195-022-00756-6.
结直肠癌（CRC）是消化道常见的恶性肿瘤。环状RNA（circRNAs）已被确定为肿瘤发生的关键调节因子。然而，circ_0004585在结直肠癌中的作用和潜在机制尚不清楚。
通过定量实时PCR和蛋白质免疫印迹法检测circ_0004585、微小RNA-338-3p（miR-338-3p）和X连锁锌指蛋白（ZFX）的表达。采用3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2-H-四氮唑溴盐（MTT）、5-乙炔基-2'-脱氧尿苷（EdU）、流式细胞术和管形成试验评估细胞增殖、细胞周期阻滞、凋亡和血管生成。应用蛋白质免疫印迹法检测上皮-间质转化（EMT）相关蛋白和MEK/ERK信号通路相关蛋白的表达。采用异种移植模型分析肿瘤生长情况。通过双荧光素酶报告基因试验验证miR-338-3p与circ_0004585/ZFX之间的靶向关系。
在结直肠癌组织和细胞中，circ_0004585和ZFX上调，而miR-338-3p下调。沉默circ_0004585可抑制结直肠癌细胞的增殖、血管生成和EMT，并诱导细胞凋亡。同样，circ_0004585缺失可抑制肿瘤生长。circ_0004585通过隔离miR-338-3p促进结直肠癌细胞的发展。此外，miR-338-3p通过靶向ZFX阻碍结直肠癌细胞的恶性进展。circ_0004585通过调节ZFX激活MEK/ERK通路。
circ_0004585通过调节miR-338-3p/ZFX/MEK/ERK通路促进结直肠癌进展，这可能为结直肠癌提供一个潜在的治疗靶点。
在线版本包含可在10.1007/s12195-022-00756-6获取的补充材料。
