CUL4A promotes the invasion of cervical cancer cells by regulating NF-κB signaling pathway

Q. Mei, L.-J. Ye, H. Lin, C.-Y. Chen

Department of Medical Oncology, The First People’s Hospital of Wenling, Zhejiang, China. wlyyccy08@163.com

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• Oncology

OBJECTIVE: The aim of this study was to investigate the effects of cullin 4A (CUL4A) on promoting the proliferation and inhibiting the apoptosis of cervical cancer (CC) cells by regulating the nuclear factor-kappa B (NF-κB) signaling pathway.

PATIENTS AND METHODS: The protein expressions of CUL4A and NF-κB in 75 CC tissues were detected through immunohistochemistry. The correlation between the expressions of the two proteins in CC tissues was analyzed via Spearman’s correlation test. Meanwhile, the prognostic significance of CUL4A expression for CC patients was analyzed by Kaplan-Meier curve. CUL4A small interfering ribonucleic acid (siRNA) was transfected into CC cells (HeLa) to downregulate the expression level of CUL4A. Subsequently, the effects of CUL4A on the proliferation and apoptosis of HeLa cells were detected by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Finally, the effect of CUL4A on the activity of the NF-κB signaling pathway was analyzed through quantitative Real Time-Polymerase Chain Reaction (qRT-PCR).

RESULTS: The protein expressions of CUL4A and NF-κB in CC tissues were significantly higher than those in normal tissues (p<0.01). The results of the survival curve showed that the prognosis of CC patients with highly expressed CUL4A is poor (p<0.001). Meanwhile, lowly expressed CUL4A protein significantly inhibited the proliferation and promoted the apoptosis of HeLa cells (p<0.01). QRT-PCR results indicated that the relative messenger RNA (mRNA) expression levels of downstream genes of the NF-κB signaling pathway were significantly lower in CC cells than those in the control group (p<0.001). In addition, CUL4A expression was positively correlated with NF-κB expression in CC (p<0.001).

CONCLUSIONS: CUL4A promotes the invasion of CC cells through the NF-κB signaling pathway.

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