Upregulation of CISD2 augments ROS homeostasis and contributes to tumorigenesis and poor prognosis of lung adenocarcinoma

被引:36
作者
Li, Shih-Miao [1 ,2 ,3 ]
Chen, Chung-Hsing [3 ]
Chen, Ya-Wen [3 ]
Yen, Yi-Chen [3 ]
Fang, Wen-Tsen [3 ]
Tsai, Fang-Yu [3 ]
Chang, Junn-Liang [4 ,5 ]
Shen, Ying-Ying [6 ]
Huang, Shiu-Feng [7 ]
Chuu, Chih-Pin [8 ,9 ]
Chang, I-Shou [3 ]
Hsiung, Chao A. [1 ,2 ]
Jiang, Shih Sheng [3 ]
机构
[1] Natl Tsing Hua Univ, Inst Bioinformat & Struct Biol, Hsinchu, Taiwan
[2] Natl Hlth Res Inst, Inst Populat Hlth Sci, Miaoli, Taiwan
[3] Natl Hlth Res Inst, Natl Inst Canc Res, Miaoli, Taiwan
[4] Taoyuan Armed Forces Gen Hosp, Dept Pathol & Lab Med, Taoyuan, Taiwan
[5] Ming Chuang Univ, Biomed Engn Dept, Taipei, Taiwan
[6] Natl Hlth Res Inst, Pathol Core Lab, Miaoli, Taiwan
[7] Natl Hlth Res Inst, Inst Mol & Genom Med, Miaoli, Taiwan
[8] Natl Hlth Res Inst, Inst Cellular & Syst Med, Miaoli, Taiwan
[9] China Med Univ, Grad Program Aging, Taichung, Taiwan
来源
SCIENTIFIC REPORTS | 2017年 / 7卷
关键词
TRANSCRIPTION FACTOR EGR1; HUMAN GASTRIC-CANCER; DOWN-REGULATION; CELL; PROTEIN; EXPRESSION; PTEN; GENE; CARCINOMA; MITONEET;
D O I
10.1038/s41598-017-12131-x
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
CISD2 is a redox-sensitive gene critical for normal development and mitochondrial integrity. CISD2 was known to have aberrant expression in several types of human cancers. However, its relation with lung cancer is still not clear. In this study we found CISD2 mRNA was significantly upregulated in lung adenocarcinoma (ADC) samples, compared with their adjacent normal counterparts, and was correlated with tumor stage, grade, and prognosis based on analysis of clinical specimens-derived expression data in public domain and our validation assay. Cell based assay indicated that CISD2 expression regulated accumulation of reactive oxygen species (ROS), polarization of mitochondrial membrane potential, as well as cell viability, apoptosis, invasiveness, and tumorigenicity. In addition, CISD2 expression was found significantly correlated with stress response/redox signaling genes such as EGR1 and GPX3, while such correlations were also found valid in many public domain data. Taken together, upregulation of CISD2 is involved in an increased antioxidant capacity in response to elevated ROS levels during the formation and progression of lung ADC. The molecular mechanism underlying how CISD2 regulates ROS homeostasis and augments malignancy of lung cancer warrants further investigations.
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页数:13
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