Oncotarget

Research Papers:

p53 increase mitochondrial copy number via up-regulation of mitochondrial transcription factor A in colorectal cancer

Shilei Wen, Jinhang Gao, Linhao Zhang, Hongying Zhou, Dingzhi Fang and Shi Feng _

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Oncotarget. 2016; 7:75981-75995. https://doi.org/10.18632/oncotarget.12514

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Abstract

Shilei Wen1,*, Jinhang Gao2,3,*, Linhao Zhang3, Hongying Zhou1, Dingzhi Fang4, Shi Feng1

1Department of Human Anatomy, School of Preclinical and Forensic Medicine, West China Medicine College, Sichuan University, Chengdu 610041, China

2Division of Peptides Related with Human Diseases, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, China

3Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu 610041, China

4Department of Biochemistry and Molecular Biology, School of Preclinical and Forensic Medicine, West China Medicine College, Sichuan University, Chengdu 610041, China

*These authors have contributed equally to this work

Correspondence to:

Shi Feng, email: jetmork@126.com

Dingzhi Fang, email: dzfang@scu.edu.cn

Keywords: colorectal cancer, p53, mitochondrial transcription factor A, mitochondrial DNA copy number

Received: April 06, 2016    Accepted: September 27, 2016    Published: October 07, 2016

ABSTRACT

In colorectal cancer, no study has been carried out discovering the relationship among p53, mitochondrial transcription factor A (TFAM) expression and change of mitochondrial DNA (mtDNA) copy number. In our study, co-expression of p53 and TFAM was observed in colon adenocarcinoma tissues, paracancerous tissues and 9 colorectal cancer cell lines. Then, a significant linear correlation was established between either p53 or TFAM expression and advanced TNM stage, positive lymph nodes and low 5-year survival rate in patients with colon adenocarcinoma. Additionally, advanced TNM stage, large tumor burden, presence of distant metastasis, and high TFAM expression were significantly related to poor overall 5-years survival. Moreover, alteration of p53 expression could change TFAM expression but TFAM could not influence p53 expression, and p53 could enhance TFAM expression via binding to TFAM promoter. While, both of p53 and TFAM expression could incrase mtDNA copy number in vitro. In conclusions, p53 might incrase mtDNA copy number through its regulation on TFAM expression via TFAMpromoter.


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