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.
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.
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.
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.
European review for medical and pharmacological sciences. 2018 Oct [Epub]
P Wang, L-D Zhang, M-C Sun, W-D Gu, H-Z Geng
Department of Urology, Heze Municipal Hospital, Heze, China. .