MicroRNA-206 facilitates gastric cancer cell apoptosis and suppresses cisplatin resistance by targeting MAPK2 signaling pathway

Z. Chen, Y.-J. Gao, R.-Z. Hou, D.-Y. Ding, D.-F. Song, D.-Y. Wang, Y. Feng

Department of Nephrology, First Hospital of Jilin University, Changchun, Jilin, China. m066682864282@sina.com

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• Oncology

OBJECTIVE: Mitogen activating protein kinase 3 (MAPK3) is critical in extracellular signal-regulated kinase (ERK)/MAPK pathway. Gastric cancer tissues have microRNA-206 (miR-206) down-regulation. This study aimed to investigate the role of miR-206 in MAPK3 expression, gastric cancer cell proliferation, apoptosis, and cisplatin (DDP) resistance.

MATERIALS AND METHODS: Dual-Luciferase reporter gene assay confirmed targeted regulation between miR-206 and MAPK3. DDP resistant cell line BGC823/DDP and SGC7901/DDP were generated for comparing miR-206 and MAPK3 expression against parental cells using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) and Western blot, followed by flow cytometry measuring apoptosis. Drug-resistant cells were transfected with miR-206 mimic for measuring MAPK3 and phosphorylated MAPK3 (p-MAPK3) expression. Flow cytometry and EdU were employed for measuring cell apoptosis and proliferation.

RESULTS: Targeted regulation existed between miR-206 and MAPK3 mRNA. BGC823/DDP and SGC7901/DDP cell presented lower miR-206 than parental cells, plus higher MAPK3 mRNA or protein. Under DDP treatment equivalent to IC50 of parental cells, drug-resistant cells presented lower apoptosis compared to parental drug-sensitive cells. Compared to miR-normal control (miR-NC) group, miR-206 mimic transfection significantly decreased MAPK3 and p-MAPK3 protein expression (p < 0.05), enhanced cell apoptosis and weakened proliferation potency (p < 0.05).

CONCLUSIONS: The down-regulation of miR-206 is associated with DDP resistance of gastric cancer cells. Up-regulating miR-2016 expression can weaken the proliferation of drug-resistant gastric cancer cells, facilitate cell apoptosis and decrease DDP resistance via targeted inhibition of MAPK3 expression.

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