Mechanisms of miR-448-Mediated Inhibition of Malignant Behaviors in Gastric Cancer Cells Through Downregulation of ADAM10 Expression

Xiuqiong YANG; Liping AI; Jiahao LUO; Jiamiao LI; Xianmin HUANG; Mengyang MA; Xiaosong HUANG; Xuesong WU

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Article Navigation > Journal of Kunming Medical University > 2026 > Accepted Manuscript

Xiuqiong YANG, Liping AI, Jiahao LUO, Jiamiao LI, Xianmin HUANG, Mengyang MA, Xiaosong HUANG, Xuesong WU. Mechanisms of miR-448-Mediated Inhibition of Malignant Behaviors in Gastric Cancer Cells Through Downregulation of ADAM10 Expression[J]. Journal of Kunming Medical University.

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Mechanisms of miR-448-Mediated Inhibition of Malignant Behaviors in Gastric Cancer Cells Through Downregulation of ADAM10 Expression

1.
Department of Pharmaceuticals and Medical Equipment，Welfare Hospital of Kunming Municipal Social Welfare Institute，Kunming Yunnan 650101
2.
Department of Gastrointestinal Surgery，The Second Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650101，China

Received Date: 2026-01-24

Abstract

Abstract

Objective To investigate the regulatory role and mechanism of miR-448 and ADAM10 in the malignant phenotype of MGC-803 gastric cancer cells. Methods RT-qPCR was used to compare the expression levels of miR-448 and ADAM10 in normal GES-1 cells and the gastric cancer cell lines MGC-803, MKN-7, NCI-N87. The targeting binding interaction between the two was validated by dual-luciferase reporter assay. After intervening with miR-448 expression in MGC-803 cells, cell proliferation, migration, and invasion capabilities were assessed via colony formation assays, scratch assays and Transwell assays. MGC-803 cells were co-transfected with miR-448 mimics/inhibitors and ADAM10 overexpression/interference plasmids. Changes in apoptosis and EMT-related molecular expression in MGC-803 cells were detected by flow cytometry, RT-qPCR, and Western blot. Results Compared with normal GES-1 cells, miR-448 was significantly downregulated while ADAM10 was significantly upregulated in MGC-803 cells （P < 0.01）. Dual-luciferase assay confirmed that miR-448 directly targets ADAM10. Furthermore, miR-448 overexpression inhibited MGC-803 proliferation, migration and invasion （P < 0.05）, and downregulated ADAM10 （P < 0.05）, thereby reducing the levels of N-cadherin, vimentin and MMP9 （P < 0.05）, which in turn inhibited MGC-803 migration and invasion. Simultaneously, miR-448 overexpression increased Bax and cleaved Caspase-3 levels while decreasing Bcl-2 levels, promoting MGC-803 cell apoptosis （P < 0.05）. Conclusion miR-448 may suppress the malignant phenotype of MGC-803 cells by targeting and inhibiting ADAM10.
- Gastric cancer,
- miR-448,
- ADAM10,
- MGC-803,
- Malignant phenotype

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References(25)

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