miR-21靶向PTEN调控AKT/FoxO1信号通路对胃癌细胞凋亡的机制研究

doi:10.3969/j.issn.1006-6233.2023.12.010

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Abstract Objective: To investigate the effect of miR-21 targeting PTEN to regulate AKT/FoxO1 signaling pathway on apoptosis in gastric cancer cells. Methods: Gastric cancer SGC-7901 cells were divided into miR-NC inhibitors group (SGC-7901 cells transfected with miR-NC inhibitors plasmid), miR-21 inhibitors group (SGC-7901 cells transfected with miR-21 inhibitors plasmid), miR-21 inhibitors+sh-PTEN group (SGC-7901 cells transfected with miR-21 inhibitors and sh-PTEN plasmids); and control group (SGC-7901 cells not transfected with any plasmids). qRT-PCR was performed to detect miR-21 mRNA expression in cells; CCK-8 was used to detect cell proliferation ability; Transwell assay for cell invasion shift ability; flow cytometry for apoptosis rate; protein blotting for PTEN, AKT, p-AKT, PI3K, p-PI3K, FoxO1 protein expression in cells; dual luciferase reporter for targeting relationship between miR-21 and PTEN. Results: Compared with normal human gastric mucosal epithelial cell GES-1 (1.00±0.10), the expression of miR-21 (1.89 ± 0.17) in gastric cancer cell SGC-7901 was significantly increased (P<0.05). Compared with the control group, the expression of miR-21 (0.83 ± 0.10), proliferation rate (45.31 ± 4.92)%, number of invasions (62.34 ± 5.83), and p-PI3K/PI3K (0.42 ± 0.05), p-AKT/AKT (0.51 ± 0.05) ratios were significantly reduced in the miR-21 inhibitors group, while the apoptosis rate (23.48 ± 3.51)%, PTEN (0.98 ± 0.10), and FoxO1 (0.76 ± 0.08) protein expression were significantly increased (P<0.001). Compared with the pcDNA-NC group, the cell proliferation rate (48.26 ± 5.01), number of invasive cells (65.37 ± 6.02), and p-PI3K/PI3K (0.46 ± 0.05), p-AKT/AKT (0.55 ± 0.06) ratios in the pcDNA-PTEN group were significantly reduced, while the cell apoptosis rate (25.61 ± 3.27)% and the expression of PTEN (0.91 ± 0.09) and FoxO1 (0.70 ± 0.08) proteins in the cells were increased (P<0.05). It was predicted that the 3'UTR end of PTEN had complementary binding sites with miR-21. Compared with the miR-NC group, the luciferase activity of the miR-21 group (0.32 ± 0.03) was significantly reduced (P<0.05) when transfected with wild-type PTEN (PTEN-WT). Compared with the miR-21 inhibitors group, the miR-21 inhibitors+sh-PTEN group showed a significant increase in cell proliferation rate (90.25 ± 9.14)%, invasion cell count (125.69 ± 10.31), and p-PI3K/PI3K (0.80 ± 0.08), p-AKT/AKT (0.76 ± 0.08) ratios. The apoptosis rate (6.24 ± 1.32) and the expression of PTEN (0.30 ± 0.04) and FoxO1 (0.38 ± 0.05) proteins in the cells were also decreased (P<0.001). Conclusion: Knockdown of miR-21 can target negative regulation of PTEN expression, modulate AKT/FoxO1 signaling pathway, inhibit proliferation and invasion of gastric cancer cells, and promote apoptosis.

Key words： Gastric cancer miR-21 PTEN AKT/FoxO1 signaling pathway Apoptosis

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2023.12.010 OR http://www.hbyxzzs.cn/EN/Y2023/V29/I12/1985

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