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抑制Lonp1会诱导宫颈癌细胞中的线粒体重塑和自噬抑制。

Inhibition of Lonp1 induces mitochondrial remodeling and autophagy suppression in cervical cancer cells.

作者信息

Wang Xiaona, Xu Xu, Zhao Yu, Qi Lifang, Ge Hongshan

机构信息

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China.

Department of Obstetrics and Gynecology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, China; Department of Obstetrics and Gynecology, The Fifth Affiliated Hospital of Nantong University, Taizhou, Jiangsu Province, China.

出版信息

Acta Histochem. 2023 Jan;125(1):151986. doi: 10.1016/j.acthis.2022.151986. Epub 2022 Dec 9.

Abstract

Lon protease 1(Lonp1) is an ATP-dependent protease located in the mitochondrial matrix and plays a crucial role in preserving normal mitochondrial function. Lonp1 overexpression is associated with tumorigenesis in various cancer types, including cervical cancer. In the present study, we show that the Lonp1 content is elevated in cervical cancer tissues compared to cervical paracancerous tissues. Conversely, Lonp1 knockdown suppresses cervical cancer cell proliferation, migration and invasion but promotes apoptosis. Mechanistically, Lonp1 knockdown decreases area of mitochondrial networks and induces mitochondrial depolarization. Furthermore, Lonp1 inhibition reduces the level of LC3-II/I, PINK1 and Parkin, but promotes the level of p62. Collectively, our study suggests that the anti-cancer effect caused by Lonp1 downregulation likely contributes to mitochondrial remodeling and suppression of autophagy and mitophagy.

摘要

Lon蛋白酶1(Lonp1)是一种位于线粒体基质中的ATP依赖性蛋白酶,在维持正常线粒体功能方面发挥着关键作用。Lonp1过表达与包括宫颈癌在内的多种癌症类型的肿瘤发生有关。在本研究中,我们发现与宫颈旁癌组织相比,宫颈癌组织中Lonp1含量升高。相反,Lonp1基因敲低可抑制宫颈癌细胞的增殖、迁移和侵袭,但促进细胞凋亡。从机制上讲,Lonp1基因敲低会减少线粒体网络的面积并诱导线粒体去极化。此外,Lonp1抑制会降低LC3-II/I、PINK1和Parkin的水平,但会提高p62的水平。总体而言,我们的研究表明,Lonp1下调所引起的抗癌作用可能有助于线粒体重塑以及抑制自噬和线粒体自噬。

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