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

doi:10.1016/j.bbadva.2023.100078

Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis

BBA Adv. 2023 Jan 22:3:100078. doi: 10.1016/j.bbadva.2023.100078. eCollection 2023.

Authors

Nurani Istiqamah¹, Takashi Matsuzaka^{1

2

3}, Momo Shimizu¹, Kaori Motomura¹, Hiroshi Ohno¹, Shiho Hasebe¹, Rahul Sharma¹, Yuka Okajima¹, Erika Matsuda¹, Song-Iee Han¹, Yuhei Mizunoe¹, Yoshinori Osaki¹, Yuichi Aita¹, Hiroaki Suzuki¹, Hirohito Sone⁴, Yoshinori Takeuchi¹, Motohiro Sekiya¹, Naoya Yahagi¹, Yoshimi Nakagawa⁵, Hitoshi Shimano^{1

3

6

7}

Affiliations

¹ Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
² Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.
³ AMED-CREST, Japan Agency for Medical Research and Development, Chiyoda-ku, Tokyo, Japan.
⁴ Department of Internal Medicine, Faculty of Medicine, Niigata University, Niigata, Japan.
⁵ Division of Complex Biosystem Research, Department of Research and Development, Institute of Natural Medicine, University of Toyama, Toyama, Japan.
⁶ International Institute for Integrative Sleep Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.
⁷ Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Abstract

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.

Keywords: Cell proliferation; Fatty acid; Glioblastoma; MicroRNA; Migration.