Department of Clinical Laboratory, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan, Jinshui District, Zhengzhou City, Henan, P.R. China.
Eur Rev Med Pharmacol Sci. 2020 Apr;24(8):4212-4223. doi: 10.26355/eurrev_202004_21001.
MicroRNA493-5p (miR-493-5p) appears to have an essential role in the abnormal cell proliferation and migration observed in the development and progression of various cancers. However, the function and mechanism of action of miR-493-5p in colorectal cancer (CRC) is unclear.
MiR-493-5p expression was analyzed in CRC patient tissue samples and cell lines by fluorescence quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). SW480 and Caco-2 cells were transfected with miR-493-5p mimics or treated with the phosphoinositide 3-kinase (PI3K) agonist 740Y-P. Cell proliferation was determined by colony formation and cell proliferation assays and cell migration and invasion by transwell migration and wound-healing assays. The Luciferase reporter assay was used to verify the association between the expression of miR-493-5p and PI3K activity. Expression levels of PI3K, protein kinase B(Akt), and forkhead box O 3a (FoxO3a) proteins were measured by Western blot analysis and immunofluorescence assay.
MiR-493-5p expression was significantly downregulated in CRC tissue samples and cell lines which was associated with progression of CRC. The proliferation, migration, and invasion of CRC cells were inhibited by miR-493-5p overexpression. The finding that miR-493-5p upregulation decreased PI3K, Akt, and FoxO3a protein expression revealed that it directly targets PI3K. Additionally, the miR-493-5p-mediated suppression of CRC cell proliferation, migration and invasion was counteracted by the PI3K agonist, indicating that miR-493-5p suppresses CRC progression by inhibiting the PI3K-Akt-FoxO3a signaling pathway.
MiR-493-5p suppresses the proliferation, migration, invasion, and progression of CRC via the PI3K-Akt-FoxO3a signaling pathway.
miR-493-5p（miR-493-5p）似乎在各种癌症的发生和发展过程中观察到的异常细胞增殖和迁移中发挥重要作用。然而，miR-493-5p 在结直肠癌（CRC）中的功能和作用机制尚不清楚。
通过荧光定量实时聚合酶链反应（qRT-PCR）分析 CRC 患者组织样本和细胞系中的 miR-493-5p 表达。SW480 和 Caco-2 细胞转染 miR-493-5p 模拟物或用磷酸肌醇 3-激酶（PI3K）激动剂 740Y-P 处理。通过集落形成和细胞增殖测定法测定细胞增殖，通过 Transwell 迁移和划痕愈合测定法测定细胞迁移和侵袭。荧光素酶报告基因测定法用于验证 miR-493-5p 的表达与 PI3K 活性之间的关联。通过 Western blot 分析和免疫荧光测定法测量 PI3K、蛋白激酶 B（Akt）和叉头框 O3a（FoxO3a）蛋白的表达水平。
miR-493-5p 在 CRC 组织样本和细胞系中的表达显著下调，与 CRC 的进展有关。miR-493-5p 的过表达抑制 CRC 细胞的增殖、迁移和侵袭。发现 miR-493-5p 的上调降低了 PI3K、Akt 和 FoxO3a 蛋白的表达，表明它直接靶向 PI3K。此外，PI3K 激动剂逆转了 miR-493-5p 介导的 CRC 细胞增殖、迁移和侵袭的抑制作用，表明 miR-493-5p 通过抑制 PI3K-Akt-FoxO3a 信号通路抑制 CRC 进展。
miR-493-5p 通过 PI3K-Akt-FoxO3a 信号通路抑制 CRC 的增殖、迁移、侵袭和进展。
