NUP153 通过 c-Myc 介导下调 P15 促进 HCC 细胞增殖。

NUP153 promotes HCC cells proliferation via c-Myc-mediated downregulation of P15.

机构信息

Department of Gastroenterology, Zhongnan Hospital of Wuhan University, Wuhan 430000, China; Hubei Clinical Center and Key Lab of Intestinal and Colorectal Diseases, Wuhan 430000, China.

出版信息

Dig Liver Dis. 2022 Dec;54(12):1706-1715. doi: 10.1016/j.dld.2022.02.008. Epub 2022 Mar 11.

DOI:10.1016/j.dld.2022.02.008

PMID:35288064

Abstract

BACKGROUND AND AIM

Nucleoporin NUP153 (NUP153) is involved in the regulation of nuclear transportation, mitosis, and tumor progression in various cancer cells. we aimed to investigate the roles of NUP153 in hepatocellular carcinoma (HCC).

METHODS

NUP153 expression level and its relationship with clinical prognosis were analyzed based on The Cancer Genome Atlas (TCGA). Quantitative real-time PCR (qRT-PCR), Western Blot (WB), and Immunohistochemistry (IHC) were used to assess NUP153 expression in tissues and cell lines. Loss-of-function experiments were implemented for exploring the roles of NUP153 in HCC cells. Ultimately, how NUP153 exerted biological functions was plumbed by performing rescue assays in HCC.

RESULTS

NUP153 expressed highly in HCC tissues and cell lines. Silencing NUP153 inhibited cellular multiplication, G1/S transition, migration, and triggered cytoskeletal rearrangement of Huh7 and HepG2 cells. Knockdown NUP153 caused up-regulation of mRNA and protein levels of P15, and siRNA deprivation of P15 partially reversed the function of low-level NUP153 in HCC. Meanwhile, silencing NUP153 caused down-regulation of mRNA and protein levels of c-Myc. Furthermore, the up-regulation of P15 and cell G1/S phase arrest induced by silencing NUP153 were partially reversed by overexpression of c-Myc.

CONCLUSIONS

NUP153 increases the proliferation ability of cells via the c-Myc/P15 axis in HCC.

摘要

背景与目的

核孔蛋白 NUP153（NUP153）参与多种癌细胞的核运输、有丝分裂和肿瘤进展的调控。我们旨在研究 NUP153 在肝细胞癌（HCC）中的作用。

方法

基于癌症基因组图谱（TCGA）分析 NUP153 的表达水平及其与临床预后的关系。采用定量实时 PCR（qRT-PCR）、Western Blot（WB）和免疫组织化学（IHC）检测组织和细胞系中 NUP153 的表达。通过敲低实验探索 NUP153 在 HCC 细胞中的作用。最终，通过在 HCC 中进行挽救实验探究 NUP153 发挥生物学功能的机制。

结果

NUP153 在 HCC 组织和细胞系中高表达。沉默 NUP153 抑制了 Huh7 和 HepG2 细胞的细胞增殖、G1/S 期转换、迁移，并触发了细胞骨架重排。敲低 NUP153 导致 P15 的 mRNA 和蛋白水平上调，而 P15 的 siRNA 耗竭部分逆转了低水平 NUP153 在 HCC 中的功能。同时，沉默 NUP153 导致 c-Myc 的 mRNA 和蛋白水平下调。此外，沉默 NUP153 诱导的 P15 上调和细胞 G1/S 期阻滞部分被 c-Myc 的过表达逆转。