MiR-484 Regulates the IL-6/STAT3 Signaling Pathway by Down-Regulating KLF12 to Inhibit the Malignant Progression of Cervical Cancer.

Abstract

Background: This study aimed to investigate the function of miR-484 in C33A cells, as well as its mechanism.

Methods: The mRNA expression patterns of miR-484 and Krüppel-like factor 12 (KLF12) in C33A cells were detected by quantitative reverse transcription polymerase chain reaction. MiR-484 mimics and miR-484 negative controls were transfected into C33A cells. Luciferase reporter assay was used to confirm the binding of miR-484 and KLF12. The effects of miR-484 on cell viability, migration, invasion, and apoptosis were assessed using the cell counting kit-8 assay, wound healing assay, Transwell assay, flow cytometry, and Western blot. Rescue experiments were performed by overexpressing KLF12. Western blot was utilized to examine the expression of KLF12, interleukin-6 (IL-6), Janus Kinase 2, phosphorylated-Janus Kinase 2, signal transducer and activator of transcription 3 (STAT3), and phosphorylated-STAT3 proteins.

Results: MiR-484 expression was down-regulated in C33A cells, while KLF12 was up-regulated. The luciferase reporter assay confirmed the direct binding of miR-484 to KLF12. MiR-484 inhibited the proliferation, migration, and invasion of C33A cells while promoting apoptosis. Additionally, it could inhibit the expression of KLF12 protein and the activation of the IL-6/STAT3 signaling pathway. However, KLF12 overexpression could reverse the above effects.

Conclusion: MiR-484 can specifically inhibit the KLF12-mediated IL-6/STAT3 signaling pathway, thereby suppressing the malignant biological behavior of C33A cells.