Over-expression of mir-124 inhibits MMP-9 expression and decreases invasion of renal cell carcinoma cells

P. Wang, L.-D. Zhang, M.-C. Sun, W.-D. Gu, H.-Z. Geng

Department of Urology, Heze Municipal Hospital, Heze, China. ftijqcjabded@sina.com

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• Oncology

OBJECTIVE: JAK-STAT3 signaling pathway is related to tumor invasion and metastasis that can regulate matrix metalloproteinase-9 (MMP-9) expression. MicroRNA-124 (MiR-124) was found downregulated in renal cell carcinoma. Bioinformatics analysis revealed the complementary binding site between miR-124 and 3’-UTR of signal transducers and activators of transcription 3 (STAT3). This study investigated the role of miR-124 in regulating Janus kinase (JAK)-STAT3 activity, MMP-9 expression, and renal cell carcinoma invasion.

MATERIALS AND METHODS: Luciferase assay was used to test the targeting regulatory effect of miR-124 on STAT3. MiR-124, STAT3, phosphorylated STAT3 (p-STAT3), and MMP-9 expressions were compared in HK-2, 769-P, and OS-RC-2 cells. Transwell assay was applied to evaluate cell invasion. OS-RC-2 cells were divided into control, miR-NC, miR-124 mimic, STAT3 inhibition, and miR-124 mimic+Stattic groups.

RESULTS: MiR-124 targeted inhibited STAT3 expression. OS-RC-2 cells exhibited the strongest invasive ability, followed by 769-P and HK-2 cells. STAT3, p-STAT3, and MMP-9 expressions were highest in OS-RC-2 cells, followed by 769-P and HK-2 cells. MiR-124 demonstrated the opposite expression trend. MiR-124 mimic and/or Stattic treatment attenuated cell invasion through reducing STAT3, p-STAT3, and MMP-9 levels.

CONCLUSIONS: MiR-124 down-regulation was associated with renal cancer cell OS-RC-2 invasion enhancement. Over-expression of miR-124 attenuated OS-RC-2 cell invasion by down-regulating STAT3 and MMP-9.

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