Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis
Nurani Istiqamah,
Takashi Matsuzaka,
Momo Shimizu,
Kaori Motomura,
Hiroshi Ohno,
Shiho Hasebe,
Rahul Sharma,
Yuka Okajima,
Erika Matsuda,
Song-Iee Han,
Yuhei Mizunoe,
Yoshinori Osaki,
Yuichi Aita,
Hiroaki Suzuki,
Hirohito Sone,
Yoshinori Takeuchi,
Motohiro Sekiya,
Naoya Yahagi,
Yoshimi Nakagawa,
Hitoshi Shimano
Affiliations
Nurani Istiqamah
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Takashi Matsuzaka
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan; Corresponding authors.
Momo Shimizu
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Kaori Motomura
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Hiroshi Ohno
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Shiho Hasebe
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Rahul Sharma
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Yuka Okajima
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Erika Matsuda
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Song-Iee Han
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Yuhei Mizunoe
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Yoshinori Osaki
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Yuichi Aita
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Hiroaki Suzuki
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Hirohito Sone
Department of Internal Medicine, Faculty of Medicine, Niigata University, Niigata, Japan
Yoshinori Takeuchi
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Motohiro Sekiya
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Naoya Yahagi
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan
Yoshimi Nakagawa
Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama, Japan
Hitoshi Shimano
Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan; International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan; Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan; Corresponding authors.
ELOVL fatty acid elongase 6 (ELOVL6) controls cellular fatty acid (FA) composition by catalyzing the elongation of palmitate (C16:0) to stearate (C18:0) and palmitoleate (C16:1n-7) to vaccinate (C18:1n-7). Although the transcriptional regulation of ELOVL6 has been well studied, the post-transcriptional regulation of ELOVL6 is not fully understood. Therefore, this study aims to evaluate the role of microRNAs (miRNAs) in regulating human ELOVL6. Bioinformatic analysis identified five putative miRNAs: miR-135b-5p, miR-135a-5p, miR-125a-5p, miR-125b-5p, and miR-22–3p, which potentially bind ELOVL6 3′-untranslated region (UTR). Results from dual-luciferase assays revealed that these miRNAs downregulate ELOVL6 by directly interacting with the 3′-UTR of ELOVL6 mRNA. Moreover, miR-135b-5p and miR-135a-5p suppress cell proliferation and migration in glioblastoma multiforme cells by inhibiting ELOVL6 at the mRNA and protein levels. Taken together, our results provide novel regulatory mechanisms for ELOVL6 at the post-transcriptional level and identify potential candidates for the treatment of patients with glioblastoma multiforme.
