Down-Regulating Overexpressed Human Lon in Cervical Cancer Suppresses Cell Proliferation and Bioenergetics

被引：46

作者：

Nie, Xiaobo ^{[1
,2
]}

Li, Min ^{[2
]}

Lu, Bin ^{[1
]}

Zhang, Yuxin ^{[1
]}

Lan, Linhua ^{[1
]}

Chen, Lin ^{[1
]}

Lu, Jianxin ^{[1
]}

机构：

[1] Wenzhou Med Univ, Zhejiang Prov Key Lab Med Genet, Sch Lab Med & Life Sci, Key Lab Lab Med,Minist Educ China, Wenzhou, Zhejiang, Peoples R China

[2] Rutgers State Univ, New Jersey Med Sch, Dept Biochem & Mol Biol, Newark, NJ 07102 USA

来源：

PLOS ONE | 2013年 / 8卷 / 11期

关键词：

ATP-DEPENDENT PROTEASE; HUMAN PAPILLOMA-VIRUS; PROTEOMIC ANALYSIS; MITOCHONDRIAL LON; EXPRESSION; PREVENTION; SURVIVAL; ROLES; GENE;

D O I：

10.1371/journal.pone.0081084

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The human mitochondrial ATP-dependent Lon protease functions in regulating the metabolism and quality control of proteins and mitochondrial DNA (mtDNA). However, the role of Lon in cancer is not well understood. Therefore, this study was undertaken to investigate the importance of Lon in cervical cancer cells from patients and in established cell lines. Microarray analysis from 30 cancer and 10 normal cervical tissues were analyzed by immunohistochemistry for Lon protein levels. The expression of Lon was also examined by immunoblotting 16 fresh cervical cancer tissues and their respective non-tumor cervical tissues. In all cases, Lon expression was significantly elevated in cervical carcinomas as compared to normal tissues. Augmented Lon expression in tissue microarrays did not vary between age, tumor-node-metastasis grades, or lymph node metastasis. Knocking down Lon in HeLa cervical cancer cells by lentivrial transduction resulted in a substantial decrease in both mRNA and protein levels. Such down-regulation of Lon expression significantly blocked HeLa cell proliferation. In addition, knocking down Lon resulted in decreased cellular bioenergetics as determined by measuring aerobic respiration and glycolysis using the Seahorse XF24 extracellular flux analyzer. Together, these data demonstrate that Lon plays a potential role in the oncogenesis of cervical cancer, and may be a useful biomarker and target in the treatment of cervical cancer. Lon; immunohistochemistry; cervical cancer; cell proliferation; cellular bioenergetics.

引用

页数：9

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