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Journal of Cellular and Molecular Medicine Volume 23 ,Issue 7 ,2019-05-06
Down‐regulation of TFAM increases the sensitivity of tumour cells to radiation via p53/TIGAR signalling pathway
ORIGINAL ARTICLES
Xu Jiang 1 , 2 Jun Wang 1
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DOI:10.1111/jcmm.14350
Received 2019-01-15, accepted for publication 2019-04-10, Published 2019-04-10
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摘要

Abstract Mitochondrial transcription factor A (TFAM) is a key regulator of mitochondria biogenesis. Previous studies confirmed that reduced TFAM expression sensitized tumours cells to chemical therapy reagents and ionizing irradiation (IR). However, the underlying mechanisms remain largely unknown. In this study, we identified that decreased expression of TFAM impaired the proliferation of tumour cells by inducing G1/S phase arrest and reducing the expression of E2F1, phospo‐Rb, PCNA and TK1. Furthermore, we proved that knockdown of TFAM enhanced the interaction between p53 and MDM2, resulting in decreased expression of p53 and the downstream target TIGAR, and thus leading to elevated level of mitochondrial superoxide and DNA double‐strand break (DSB) which were exacerbated when treated the cell with ionizing radiation. Those indicated that knockdown of TFAM could aggravate radiation induced DSB levels through affecting the production of mitochondria derived reactive oxygen species. Our current work proposed a new mechanism that TFAM through p53/TIGAR signalling to regulate the sensitivity of tumour cells to ionizing radiation. This indicated that TFAM might be a potential target for increasing the sensitization of cancer cells to radiotherapy.

关键词

TFAM;radio‐sensitivity;p53/TIGAR signalling;mitochondrial superoxide;cell proliferation

授权许可

Copyright © 2019 Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine

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通讯作者

Jun Wang.Key Laboratory of High Magnetic Field and Ion Beam Physical Biology, Chinese Academy of Sciences, Hefei, China.wangjun0457@ipp.ac.cn

推荐引用方式

Xu Jiang,Jun Wang. Down‐regulation of TFAM increases the sensitivity of tumour cells to radiation via p53/TIGAR signalling pathway. Journal of Cellular and Molecular Medicine ,Vol.23, Issue 7(2019)

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