LONP2 在头颈部鳞状细胞癌中的作用。

Role of LONP2 in head and neck squamous cell carcinoma.

机构信息

Department of Otolaryngology, the Affiliated Hospital of Inner Mongolia Medical University, Inner Mongolia, China.

出版信息

Gene. 2023 Jan 30;851:147033. doi: 10.1016/j.gene.2022.147033. Epub 2022 Nov 5.

DOI:10.1016/j.gene.2022.147033

Abstract

Lon Peptidase 2, Peroxisomal (LONP2) is a peptidase in peroxisomes that selectively degrades oxidatively damaged proteins in cells and is upregulated in several cancers. In this study, we found both the mRNA and protein level of LONP2 was upregulated in head and neck squamous cell carcinoma (HNSCC) samples. Ectopic overexpressed LONP2 enhanced HNSCC cell growth and migration. Nevertheless, LONP2 silencing suppressed tumor growth in vitro and in vivo. It was also indicated that knockdown of LONP2 also impaired the cell cycle progression and improved apoptosis rate of HNSCC cells. The results of RNA sequencing showed that plastin 3 (PLS3) was heavily downregulated after LONP2 silencing. PLS3 is an actin-bundling protein that functions as an oncogene in several cancers. Furthermore, knockdown of PLS3 inhibited the cell proliferation induced by LONP2 overexpression. In conclusion, we identified an oncogenic effect of LONP2 on cell proliferation and migration in HNSCC via positively regulating the expression of PLS3.

摘要

Lon 肽酶 2，过氧化物酶体（LONP2）是过氧化物酶体中的一种肽酶，可选择性降解细胞中氧化损伤的蛋白质，在几种癌症中上调。在这项研究中，我们发现头颈部鳞状细胞癌（HNSCC）样本中 LONP2 的 mRNA 和蛋白水平均上调。过表达 LONP2 增强了 HNSCC 细胞的生长和迁移。然而，LONP2 沉默抑制了体外和体内肿瘤的生长。结果还表明，LONP2 的敲低也会损害 HNSCC 细胞的细胞周期进程并提高细胞凋亡率。RNA 测序的结果表明，LONP2 沉默后 plastin 3（PLS3）大量下调。PLS3 是一种肌动蛋白结合蛋白，在几种癌症中作为致癌基因发挥作用。此外，PLS3 的敲低抑制了 LONP2 过表达诱导的细胞增殖。总之，我们通过正向调节 PLS3 的表达，鉴定了 LONP2 对 HNSCC 细胞增殖和迁移的致癌作用。