NF-κB-modulated miR-130a targets TNF-α in cervical cancer cells.

BACKGROUND: Nuclear factor-κB (NF-κB) induces a variety of biological processes through transcriptional gene control whose products are components in various signaling pathways. MicroRNAs are a small endogenous non-coding RNAs that regulate gene expression and are involved in tumorigenesis. Using human cervical cancer cell lines, this study aimed to investigate whether NF-κB could regulate miR-130a expression and the functions and targets of miR-130a.

METHODS: We used the HeLa and C33A cervical cancer cell lines that were transfected with NF-κB or miR-130a overexpression plasmids to evaluate their effects on cell growth. We utilized bioinformatics, a fluorescent reporter assay, qRT-PCR and Western blotting to identify downstream target genes.

RESULTS: In HeLa and C33A cells, NF-κB and miR-130a overexpression promoted cell growth, but genetic knockdowns suppressed growth. TNF-α was identified as a target of miR-130a by binding in a 3'-untranslated region (3'UTR) EGFP reporter assay and by Western blot analysis. Furthermore, low TNF-α concentrations stimulated NF-κB activity and then induced miR-130a expression, and TNF-α overexpression rescued the effects of miR-130a on cervical cancer cells.

CONCLUSIONS: Our findings indicate that TNF-α can activate NF-κB activity, which can reduce miR-130a expression, and that miR-130a targets and downregulates TNF-α expression. Hence, we shed light on the negative feedback regulation of NF-κB/miR-130a/TNF-α/NF-κB in cervical cancer and may provide insight into the carcinogenesis of cervical cancer.