CUL4A 通过调控 NF-κB 信号通路促进宫颈癌的侵袭。

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

机构信息

Department of Medical Oncology, The First People's Hospital of Wenling, Zhejiang, China.

出版信息

Eur Rev Med Pharmacol Sci. 2020 Oct;24(20):10403-10409. doi: 10.26355/eurrev_202010_23390.

DOI:10.26355/eurrev_202010_23390

PMID:33155196

Abstract

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.

摘要

目的

本研究旨在探讨 CUL4A 通过调控核因子-κB（NF-κB）信号通路对促进宫颈癌（CC）细胞增殖和抑制凋亡的作用。

方法

采用免疫组化法检测 75 例 CC 组织中 CUL4A 和 NF-κB 的蛋白表达情况，采用 Spearman 相关检验分析 CC 组织中两蛋白表达的相关性，采用 Kaplan-Meier 曲线分析 CUL4A 表达对 CC 患者的预后意义。用 CUL4A 小干扰 RNA（siRNA）转染 CC 细胞（HeLa）下调 CUL4A 的表达水平，然后通过噻唑蓝（MTT）比色法和流式细胞术分别检测 CUL4A 对 HeLa 细胞增殖和凋亡的影响，最后通过实时定量聚合酶链反应（qRT-PCR）分析 CUL4A 对 NF-κB 信号通路活性的影响。

结果

CC 组织中 CUL4A 和 NF-κB 的蛋白表达均显著高于正常组织（p<0.01）。生存曲线结果表明，CUL4A 高表达的 CC 患者预后较差（p<0.001）。同时，低表达 CUL4A 蛋白可显著抑制 HeLa 细胞的增殖并促进其凋亡（p<0.01）。qRT-PCR 结果显示，NF-κB 信号通路下游基因的相对信使 RNA（mRNA）表达水平在 CC 细胞中显著低于对照组（p<0.001）。此外，CC 中 CUL4A 表达与 NF-κB 表达呈正相关（p<0.001）。