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

Abstract

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.

• Authors: P Wang, L-D Zhang, M-C Sun, W-D Gu, H-Z Geng
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 22 Issue 19 Pg. 6308-6314 (10 2018) ISSN: 2284-0729 [Electronic] Italy
• PMID: 30338828 (Publication Type: Journal Article)

Chemical References

• MIRN124 microRNA, human
• MicroRNAs
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Apoptosis
• Carcinoma, Renal Cell (genetics)
• Cell Line, Tumor
• Cell Proliferation
• Humans
• Kidney Neoplasms (genetics)
• Matrix Metalloproteinase 9 (genetics)
• MicroRNAs (genetics)
• Neoplasm Invasiveness