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

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

^*Corresponding author for this work

Complex Biosystem Research, Institute of Natural Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

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.

Original language	English
Article number	100078
Journal	BBA Advances
Volume	3
DOIs	https://doi.org/10.1016/j.bbadva.2023.100078
State	Published - 2023/01

Keywords

Cell proliferation
Fatty acid
Glioblastoma
MicroRNA
Migration

ASJC Scopus subject areas

Biophysics
Biochemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.bbadva.2023.100078

Cite this

Istiqamah, N., Matsuzaka, T., Shimizu, M., Motomura, K., Ohno, H., Hasebe, S., Sharma, R., Okajima, Y., Matsuda, E., Han, S. I., Mizunoe, Y., Osaki, Y., Aita, Y., Suzuki, H., Sone, H., Takeuchi, Y., Sekiya, M., Yahagi, N., Nakagawa, Y., & Shimano, H. (2023). Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis. BBA Advances, 3, Article 100078. https://doi.org/10.1016/j.bbadva.2023.100078

@article{187bbbd3dcf84c86a7fe7c4d4f7c5b71,

title = "Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis",

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",

author = "Nurani Istiqamah and Takashi Matsuzaka and Momo Shimizu and Kaori Motomura and Hiroshi Ohno and Shiho Hasebe and Rahul Sharma and Yuka Okajima and Erika Matsuda and Han, {Song Iee} and Yuhei Mizunoe and Yoshinori Osaki and Yuichi Aita and Hiroaki Suzuki and Hirohito Sone and Yoshinori Takeuchi and Motohiro Sekiya and Naoya Yahagi and Yoshimi Nakagawa and Hitoshi Shimano",

note = "Publisher Copyright: {\textcopyright} 2023 The Author(s)",

year = "2023",

month = jan,

doi = "10.1016/j.bbadva.2023.100078",

language = "英語",

volume = "3",

journal = "BBA Advances",

issn = "2667-1603",

publisher = "Elsevier B.V.",

}

Istiqamah, N, Matsuzaka, T, Shimizu, M, Motomura, K, Ohno, H, Hasebe, S, Sharma, R, Okajima, Y, Matsuda, E, Han, SI, Mizunoe, Y, Osaki, Y, Aita, Y, Suzuki, H, Sone, H, Takeuchi, Y, Sekiya, M, Yahagi, N, Nakagawa, Y & Shimano, H 2023, 'Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis', BBA Advances, vol. 3, 100078. https://doi.org/10.1016/j.bbadva.2023.100078

TY - JOUR

T1 - Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis

AU - Istiqamah, Nurani

AU - Matsuzaka, Takashi

AU - Shimizu, Momo

AU - Motomura, Kaori

AU - Ohno, Hiroshi

AU - Hasebe, Shiho

AU - Sharma, Rahul

AU - Okajima, Yuka

AU - Matsuda, Erika

AU - Han, Song Iee

AU - Mizunoe, Yuhei

AU - Osaki, Yoshinori

AU - Aita, Yuichi

AU - Suzuki, Hiroaki

AU - Sone, Hirohito

AU - Takeuchi, Yoshinori

AU - Sekiya, Motohiro

AU - Yahagi, Naoya

AU - Nakagawa, Yoshimi

AU - Shimano, Hitoshi

PY - 2023/1

Y1 - 2023/1

N2 - 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.

AB - 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.

KW - Cell proliferation

KW - Fatty acid

KW - Glioblastoma

KW - MicroRNA

KW - Migration

UR - http://www.scopus.com/inward/record.url?scp=85147004222&partnerID=8YFLogxK

U2 - 10.1016/j.bbadva.2023.100078

DO - 10.1016/j.bbadva.2023.100078

M3 - 学術論文

C2 - 37082255

AN - SCOPUS:85147004222

SN - 2667-1603

VL - 3

JO - BBA Advances

JF - BBA Advances

M1 - 100078

ER -

Identification of key microRNAs regulating ELOVL6 and glioblastoma tumorigenesis

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Fingerprint

Cite this