Upregulation of CISD2 augments ROS homeostasis and contributes to tumorigenesis and poor prognosis of lung adenocarcinoma
Autor: | I-Shou Chang, Junn-Liang Chang, Shiu-Feng Huang, Chao A. Hsiung, Ying-Ying Shen, Chung-Hsing Chen, Shih Sheng Jiang, Chih-Pin Chuu, Yi-Chen Yen, Shih-Miao Li, Fang-Yu Tsai, Wen-Tsen Fang, Ya-Wen Chen |
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Rok vydání: | 2017 |
Předmět: |
Male
0301 basic medicine Lung Neoplasms lcsh:Medicine Adenocarcinoma of Lung Biology medicine.disease_cause Article 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation medicine Homeostasis Humans Viability assay lcsh:Science Lung cancer A549 cell Regulation of gene expression Multidisciplinary lcsh:R Membrane Proteins Prognosis medicine.disease Neoplasm Proteins Up-Regulation Gene Expression Regulation Neoplastic 030104 developmental biology A549 Cells Apoptosis 030220 oncology & carcinogenesis Cancer research Adenocarcinoma Female lcsh:Q Reactive Oxygen Species Carcinogenesis |
Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | 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. |
Databáze: | OpenAIRE |
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