Department of Gynaecology, The First People's Hospital of Chongqing Liang Jiang New Area, Chongqing, China.
Department of Obstetrics & Gynaecology, Southwest Hospital, Army Medical University, Chongqing, China.
J Obstet Gynaecol Res. 2021 Nov;47(11):3931-3942. doi: 10.1111/jog.14947. Epub 2021 Aug 2.
NFKBIA is frequently encountered. However, its expression and relevance of the proliferation, invasion, and migration in human cervical cancer (CC) remain unclear. The role and novel mechanism of NFKBIA in CC progression were investigated in this study.
We analyzed the expression of NFKBIA in CC and adjacent normal tissues and explored the proliferation, migration, and invasion of HeLa cells by treating with either wild-type NFKBIA plasmid or NFKBIA siRNA. Effect of NFKBIA on the epithelial-mesenchymal transition (EMT) and the β-catenin-mediated transcription of target genes were evaluated subsequently.
NFKBIA expression was lower in CC tissues than that of adjacent tissues. An obvious dysregulation of NFKBIA overexpression was revealed in CC cell proliferation, invasion, and migration, which differed from the effect of knockdown NFKBIA. NFKBIA overexpression facilitated the expression of both phosphorylated β-catenin and E-cadherin protein. It inhibited the expression of vimentin, TWIST, as well as downstream targets of β-catenin including c-MYC, TCF-4 and MMP14. Conversely, NFKBIA silencing elevated the expression of c-MYC, TCF-4, and MMP14, and promoted the EMT in HeLa cells. Both endogenous and exogenous NFKBIA interacted with β-catenin. Moreover, β-catenin overexpression stemmed effects of NFKBIA on the proliferation, migration, and invasion of HeLa cells. By overexpressing NFKBIA in vivo, the volume and size of tumors were notably decreased, while no obvious alteration was found in mice body weight.
By inhibiting β-catenin-mediated transcription, NFKBIA functioning as a tumor suppressor might be introduced as a novel anti-metastatic agent for the treatment of targeted CC.
NFKBIA 经常出现。然而，其在人宫颈癌（CC）中的表达及其与增殖、侵袭和迁移的相关性尚不清楚。本研究旨在探讨 NFKBIA 在 CC 进展中的作用和新机制。
我们分析了 NFKBIA 在 CC 组织和相邻正常组织中的表达，并通过转染野生型 NFKBIA 质粒或 NFKBIA siRNA 研究其对 HeLa 细胞增殖、迁移和侵袭的影响。随后评估 NFKBIA 对上皮-间质转化（EMT）和 β-连环蛋白介导的靶基因转录的影响。
NFKBIA 在 CC 组织中的表达低于相邻组织。CC 细胞增殖、侵袭和迁移中明显存在 NFKBIA 过表达的失调，这与 NFKBIA 敲低的作用不同。NFKBIA 过表达促进了磷酸化 β-连环蛋白和 E-钙黏蛋白蛋白的表达。它抑制了波形蛋白、TWIST 以及 β-连环蛋白下游靶基因 c-MYC、TCF-4 和 MMP14 的表达。相反，NFKBIA 沉默会增加 c-MYC、TCF-4 和 MMP14 的表达，并促进 HeLa 细胞 EMT。内源性和外源性 NFKBIA 均与 β-连环蛋白相互作用。此外，β-连环蛋白过表达会影响 NFKBIA 对 HeLa 细胞增殖、迁移和侵袭的影响。通过体内过表达 NFKBIA，肿瘤的体积和大小明显减小，而小鼠体重无明显变化。
NFKBIA 通过抑制 β-连环蛋白介导的转录，作为肿瘤抑制因子，可能成为治疗靶向 CC 的新型抗转移药物。
