Circ‐ACAP2 facilitates the progression of colorectal cancer through mediating miR‐143‐3p/FZD4 axis

抗辐射性 小RNA 癌症研究 时尚 Wnt信号通路 生物 化学 分子生物学 细胞凋亡 细胞生长 基因敲除 细胞培养 信号转导 细胞生物学 程序性细胞死亡 半胱氨酸蛋白酶 遗传学 基因
作者
Guifeng Zhang,Zhenhua Liu,Jiangming Zhong,Li Lin
出处
期刊:European Journal of Clinical Investigation [Wiley]
卷期号:51 (12) 被引量:18
标识
DOI:10.1111/eci.13607
摘要

Circular RNAs (circRNAs) play crucial roles in multiple cancers, including colorectal cancer (CRC). Here, we explored the role of circRNA ArfGAP with coiled-coil, ankyrin repeat and PH domains 2 (circ-ACAP2) in the progression and radioresistance of CRC.Quantitative real-time polymerase chain reaction (qPCR) and Western blot assay were used to detect RNA and protein expression, respectively. The proliferation, apoptosis, migration, invasion and radioresistance of CRC cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, transwell migration assay, transwell invasion assay and colony formation assay. The target interaction between microRNA-143-3p (miR-143-3p) and circ-ACAP2 or frizzled class receptor 4 (FZD4) was verified by dual-luciferase reporter assay. Murine xenograft model was established to explore the role of circ-ACAP2 in vivo.The expression of circ-ACAP2 was prominently enhanced in CRC tissues and cell lines. Circ-ACAP2 facilitated the proliferation, migration, invasion and radioresistance whereas inhibited the apoptosis of CRC cells. MiR-143-3p was a direct target of circ-ACAP2 in CRC cells. Circ-ACAP2 promoted the progression and radioresistance of CRC partly by sponging miR-143-3p. MiR-143-3p interacted with the 3' untranslated region (3'UTR) of FZD4 in CRC cells, and FZD4 overexpression partly reversed miR-143-3p-mediated effects in CRC cells. Wnt/β-catenin signalling was modulated by circ-ACAP2/miR-143-3p/FZD4 axis in CRC cells.Circ-ACAP2 contributed to the development and radioresistance of CRC partly through targeting miR-143-3p/FZD4 axis, which provided novel potential diagnostic and therapeutic targets for CRC.
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