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

BBA Advances (Jan 2023)

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.

Journal volume & issue: Vol. 3
p. 100078

Abstract

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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.

Published in BBA Advances

ISSN: 2667-1603 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry; Science: Biology (General): Genetics
Website: https://www.journals.elsevier.com/bba-advances

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