期刊
JOURNAL OF TRANSLATIONAL MEDICINE
卷 12, 期 -, 页码 -出版社
BMC
DOI: 10.1186/1479-5876-12-155
关键词
miRNA; miRNA-130a; NF-kappa B; Cervical cancer; TNF-alpha
资金
- National Natural Science Foundation of China [31270818, 91029714, 31071191, 31101000]
- Natural Science Foundation of Tianjin [12JCZDJC25100, 09JCZDJC17500]
Background: Nuclear factor-kappa B (NF-kappa B) 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-kappa B could regulate miR-130a expression and the functions and targets of miR-130a. Methods: We used the HeLa and C(33)A cervical cancer cell lines that were transfected with NF-kappa B 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-kappa B and miR-130a overexpression promoted cell growth, but genetic knockdowns suppressed growth. TNF-alpha 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-alpha concentrations stimulated NF-kappa B activity and then induced miR-130a expression, and TNF-alpha overexpression rescued the effects of miR-130a on cervical cancer cells. Conclusions: Our findings indicate that TNF-alpha can activate NF-kappa B activity, which can reduce miR-130a expression, and that miR-130a targets and downregulates TNF-alpha expression. Hence, we shed light on the negative feedback regulation of NF-kappa B/miR-130 alpha/TNF-alpha/NF-kappa B in cervical cancer and may provide insight into the carcinogenesis of cervical cancer.
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