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Romo1 is associated with ROS production and cellular growth in human gliomas

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Abstract

Romo1 is a mitochondrial protein whose elevated expression is commonly observed in various types of human cancers. However, the expression status of Romo1 and its implication in the pathogenesis of human glioblastoma (GBM) remain largely undefined. To understand the role of Romo1 in the progression of GBM, we explored its expression in a series of GBM tissues and cell lines and determined its effect on ROS production, cell proliferation, and tumor growth. Romo1 was frequently overexpressed at the mRNA level in both primary tumors and cell lines and its elevation was more commonly observed in high grade tumors versus low grade tumors. Romo1 expression was associated with ROS production and its knockdown led to a marked reduction of in vitro cellular growth and anchorage-independent growth of GBM. Consistently, Romo1 depletion induced a G2/M arrest of the cell cycle that was accompanied with accumulation of phospho-cdc2. Furthermore, a mouse xenograft assay revealed that Romo1 depletion significantly decreased tumor formation and growth. Therefore, our data demonstrate that Romo1 upregulation is a common event in human GBMs and contributes to the malignant tumor progression, suggesting that Romo1 could be a new therapeutic target for human GBM.

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Acknowledgments

This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2010-0009959).

Conflict of interest

None.

Ethical standards

The animal experiment was approved by Committees at the Korea university and tissue samples were collected after obtain patients’ informed consent.

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Authors and Affiliations

  1. Department of Neurosurgery College of Medicine, Korea University, #126, 5-ga, Anam-Dong, Seongbuk-Gu, Seoul, 136-705, Korea

    Mi Ok Yu, Na-Hyun Song, Kyung-Jae Park, Dong-Hyuk Park, Yong-Gu Chung & Shin-Hyuk Kang

  2. School of Life Sciences and Biotechnology, Korea University, 5-1 Anam-Dong, Seongbuk-Gu, Seoul, 136-701, Korea

    Mi Ok Yu & Sung-Gil Chi

  3. Department of Pathology, College of Medicine, Korea University, Seoul, Korea

    Yang-Seok Chae

  4. Department of Neurosurgery, Ajou University School of Medicine, Suwon, Kyunggi-Do, Korea

    Se-Hyuk Kim

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Correspondence to Shin-Hyuk Kang.

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11060_2014_1608_MOESM1_ESM.docx

Validation of knockdown effect of lentiviral transfection of Romo1 shRNAs. a Comparison of knockdown effect of four different shRNAs. GBM cells were infected with lentivirus containing control shRNA and four different Romo1 shRNAs (1-4). At 24 h after infection, Romo1 levels were determined. b Knockdown effect of shRNA-1 on Romo1 expression

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Yu, M.O., Song, NH., Park, KJ. et al. Romo1 is associated with ROS production and cellular growth in human gliomas. J Neurooncol 121, 73–81 (2015). https://doi.org/10.1007/s11060-014-1608-x

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