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Theranostics 2017; 7(15):3624-3637. doi:10.7150/thno.21408 This issue Cite

Research Paper

Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression

Mi Hee Park1*, Hyung-Mun Yun2*, Chul Ju Hwang1, Sang Ick Park3, Sang Bae Han1, Dae Youn Hwang4, Do-Young Yoon5, Sanghyeon Kim6, Jin Tae Hong1✉

1. College of Pharmacy and Medical Research Center, Chungbuk National University, 12, Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Republic of Korea;
2. Department of Oral and Maxillofacial Pathology, School of Dentistry, Kyung Hee University, 1 Heogi-Dong, Dongdaemun-Gu, Seoul, 130-701, Republic of Korea;
3. Center for Biomedical Sciences, Korea National Institute of Health, Cheongju 28159, Republic of Korea;
4. Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang-si, Gyeongsangnam‑do 627‑706, Republic of Korea;
5. Department of Bioscience and Biotechnology, Bio/Molecular Informatics Center, Konkuk University, Gwangjin-gu, Seoul 143-701, Republic of Korea;
6. Stanley Brain Research Laboratory, Stanley Medical Research Institute, 9800 Medical Center Drive, Rockville, MD 20850.
* These authors equally contributed to this work.

✉ Corresponding author: Dr. Jin Tae Hong, College of Pharmacy and Medical Research Center, Chungbuk National University, 48 Gaeshin-dong, Heungduk-gu, Cheongju, Chungbuk 361-763, Korea; Tel: 82-043-261-2813, Fax: 82-043-268-2732, Email: jinthongac.kr More

Citation:
Park MH, Yun HM, Hwang CJ, Park SI, Han SB, Hwang DY, Yoon DY, Kim S, Hong JT. Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression. Theranostics 2017; 7(15):3624-3637. doi:10.7150/thno.21408. https://www.thno.org/v07p3624.htm
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Abstract

Graphic abstract

Some epidemiological studies suggest an inverse correlation between cancer incidence and Alzheimer's disease (AD). In this study, we demonstrated experimental evidences for this inverse relationship. In the co-expression network analysis using the microarray data and GEO profile of gene expression omnibus data analysis, we showed that the expression of peroxiredoxin 6 (PRDX6), a tumor promoting protein was significantly increased in human squamous lung cancer, but decreased in mutant presenilin 2 (PS2) containing AD patient. We also found in animal model that mutant PS2 transgenic mice displayed a reduced incidence of spontaneous and carcinogen-induced lung tumor development compared to wildtype transgenic mice. Agreed with network and GEO profile study, we also revealed that significantly reduced expression of PRDX6 and activity of iPLA2 in these animal models. PS2 mutations increased their interaction with PRDX6, thereby increasing iPLA2 cleavage via increased γ-secretase leading to loss of PRDX6 activity. However, knockdown or inhibition of γ-secretase abolished the inhibitory effect of mutant PSs. Moreover, PS2 mutant skin fibroblasts derived from patients with AD showed diminished iPLA2 activity by the elevated γ-secretase activity. Thus, the present data suggest that PS2 mutations suppress lung tumor development by inhibiting the iPLA2 activity of PRDX6 via a γ-secretase cleavage mechanism and may explain the inverse relationship between cancer and AD incidence.

Keywords: Presenilin, Alzheimer's disease, PRDX6, iPLA2, lung cancer.

Citation styles

APA
Park, M.H., Yun, H.M., Hwang, C.J., Park, S.I., Han, S.B., Hwang, D.Y., Yoon, D.Y., Kim, S., Hong, J.T. (2017). Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression. Theranostics, 7(15), 3624-3637. https://doi.org/10.7150/thno.21408.

ACS
Park, M.H.; Yun, H.M.; Hwang, C.J.; Park, S.I.; Han, S.B.; Hwang, D.Y.; Yoon, D.Y.; Kim, S.; Hong, J.T. Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression. Theranostics 2017, 7 (15), 3624-3637. DOI: 10.7150/thno.21408.

NLM
Park MH, Yun HM, Hwang CJ, Park SI, Han SB, Hwang DY, Yoon DY, Kim S, Hong JT. Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression. Theranostics 2017; 7(15):3624-3637. doi:10.7150/thno.21408. https://www.thno.org/v07p3624.htm

CSE
Park MH, Yun HM, Hwang CJ, Park SI, Han SB, Hwang DY, Yoon DY, Kim S, Hong JT. 2017. Presenilin Mutation Suppresses Lung Tumorigenesis via Inhibition of Peroxiredoxin 6 Activity and Expression. Theranostics. 7(15):3624-3637.

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