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Survival of lung cancer patients is prolonged with higher regucalcin gene expression: suppressed proliferation of lung adenocarcinoma A549 cells in vitro

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Abstract

Regucalcin plays a crucial role as a suppressor of transcription signaling, and its diminished expression or activity may play a key role in human carcinogenesis. Higher regucalcin expression has been demonstrated to prolong survival of the patients of pancreatic cancer, breast cancer, and hepatocellular carcinoma. Moreover, we investigated an involvement of regucalcin in human lung cancer. Human non-small cell lung cancer (NSCLC) accounts for over 80% in human lung cancer and is one of the leading causes of malignancy-related mortality with fewer than 16% patients surviving beyond 5 years. In this study, gene expression and survival data of 204 lung adenocarcinoma patients were obtained through the gene expression omnibus database (GSE31210) for outcome analysis. Gene expression data demonstrated that prolonged survival in lung cancer patients is associated with higher regucalcin gene expression. Overexpression of regucalcin suppressed the proliferation, cell death, and migration of human lung adenocarcinoma NSCLC A549 cells in vitro. Mechanistically, regucalcin induced G1 and G2/M phase cell cycle arrest of A549 cells through suppression of multiple signaling pathways including Ras, Akt, MAP kinase, and SAPK/JNK. Moreover, overexpression of regucalcin caused decreases in the oncogenes c-fos and c-myc and elevation of the tumor suppressers p53 and Rb. These findings suggest that regucalcin may play a potential role as a suppressor of human lung cancer, and that downregulation of regucalcin expression may predispose patients to development of lung cancer. Overexpression of regucalcin using gene delivery may constitute a novel therapeutic approach to treating lung cancer.

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Authors and Affiliations

  1. Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, 1365 C Clifton Road, Atlanta, 30322, USA

    Masayoshi Yamaguchi & Mamoru Shoji

  2. Department of Neurosurgery, Winship Cancer Institute, Emory University School of Medicine, 1365 C Clifton Road, Atlanta, USA

    Satoru Osuka

  3. The Atlanta Department of Veterans Affairs Medical Center, Decatur, GA, USA

    M. Neale Weitzmann

  4. Division of Endocrinology & Metabolism & Lipids, Department of Medicine, Emory University School of Medicine, 101 Woodruff Circle, 1329 WMRB, Atlanta, GA, 30322, USA

    M. Neale Weitzmann

  5. Laboratory of Analytical Neurobiology, Faculty of Pharmacy, Meijo University, Yagotoyama 150, Tempaku, Nagoya, 468-8503, Japan

    Tomiyasu Murata

Authors
  1. Masayoshi Yamaguchi
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  2. Satoru Osuka
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  3. Mamoru Shoji
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  4. M. Neale Weitzmann
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  5. Tomiyasu Murata
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Correspondence to Masayoshi Yamaguchi.

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Yamaguchi, M., Osuka, S., Shoji, M. et al. Survival of lung cancer patients is prolonged with higher regucalcin gene expression: suppressed proliferation of lung adenocarcinoma A549 cells in vitro. Mol Cell Biochem 430, 37–46 (2017). https://doi.org/10.1007/s11010-017-2952-x

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  • DOI: https://doi.org/10.1007/s11010-017-2952-x

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