Evidence for a Role of the Transcriptional Regulator Maid in Tumorigenesis and Aging

Koichi Fujisawa; Shuji Terai; Toshihiko Matsumoto; Taro Takami; Naoki Yamamoto; Hiroshi Nishina; Makoto Furutani-Seiki; Isao Sakaida

doi:10.1371/journal.pone.0129950

Evidence for a Role of the Transcriptional Regulator Maid in Tumorigenesis and Aging

PLoS One. 2015 Jun 24;10(6):e0129950. doi: 10.1371/journal.pone.0129950. eCollection 2015.

Authors

Koichi Fujisawa¹, Shuji Terai², Toshihiko Matsumoto³, Taro Takami³, Naoki Yamamoto³, Hiroshi Nishina⁴, Makoto Furutani-Seiki⁵, Isao Sakaida¹

Affiliations

¹ Center for Reparative Medicine, Yamaguchi University School of Medicine, Minami Kogushi 1-1-1, Ube Yamaguchi 755-8505, Japan; Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube Yamaguchi 755-8505, Japan.
² Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube Yamaguchi 755-8505, Japan; Division of Gastroenterology and Hepatology, Graduate School of Medical and Dental Sciences, Niigata University, 1-757 Asahimachidori, Chuo-Ku, Niigata 951-8510, Japan.
³ Department of Gastroenterology and Hepatology, Yamaguchi University Graduate School of Medicine, Minami Kogushi 1-1-1, Ube Yamaguchi 755-8505, Japan.
⁴ Department of Developmental and Regenerative Biology, Medical Research Institute, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan.
⁵ Department of Biology and Biochemistry, University of Bath, Bath BA2 7AY, United Kingdom.

Abstract

Maid is a helix-loop-helix protein that is involved in cell proliferation. In order to further elucidate its physiological functions, we studied Maid activity in two small fish model systems. We found that Maid expression was greatest in zebrafish liver and that it increased following partial hepatectomy. Maid levels were also high in hepatic preneoplastic foci induced by treatment of zebrafish with diethylnitrosamine (DEN), but low in hepatocellular carcinomas (HCC), mixed tumors, and cholangiocarcinomas developing in these animals. In DEN-treated transgenic medaka overexpressing Maid, hepatic BrdU uptake and proliferation were reduced. After successive breedings, Maid transgenic medaka exhibited decreased movement and a higher incidence of abnormal spine curvature, possibly due to the senescence of spinal cord cells. Taken together, our results suggest that Maid levels can influence the progression of liver cancer. In conclusion, we found that Maid is important regulator of hepatocarconogenesis and aging.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / genetics*
Amino Acid Sequence
Animals
Animals, Genetically Modified
Carcinogenesis / genetics*
Carcinoma, Hepatocellular / metabolism
Cell Line
Cell Transformation, Neoplastic*
Diethylnitrosamine / chemistry
Disease Models, Animal
Disease Progression
Gene Expression Profiling
Gene Expression Regulation, Neoplastic*
Humans
Liver Neoplasms / metabolism
Mice
Molecular Sequence Data
Oligonucleotide Array Sequence Analysis
Oryzias
Phylogeny
Sequence Homology, Amino Acid
Transcription Factors / genetics
Transcription Factors / physiology*
Zebrafish
Zebrafish Proteins / genetics
Zebrafish Proteins / physiology*

Substances

Transcription Factors
Zebrafish Proteins
ccndbp1 protein, zebrafish
Diethylnitrosamine

Grants and funding

This study was supported by a Grant-in-Aid for Scientific Research (22390150), and Grants-in-Aid for Challenging Exploratory Research (22659148, 23659398、25670370) from the Japan Society for the Promotion of Science. This study was supported by Grants-in-Aid for scientific research from the Ministry of Health, Labour and Welfare, health and labour sciences research grants and Japan Science and Technology Agency (JST), the project of realization of regenerative medicine and highway.