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鉴定调控胶质母细胞瘤肿瘤发生的关键微小RNA。

Identification of key microRNAs regulating and glioblastoma tumorigenesis.

作者信息

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

机构信息

Department of Endocrinology and Metabolism, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan.

Transborder Medical Research Center, University of Tsukuba, Tsukuba, Ibaraki, Japan.

出版信息

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

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 has been well studied, the post-transcriptional regulation of is not fully understood. Therefore, this study aims to evaluate the role of microRNAs (miRNAs) in regulating human . 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 3'-untranslated region (UTR). Results from dual-luciferase assays revealed that these miRNAs downregulate by directly interacting with the 3'-UTR of mRNA. Moreover, miR-135b-5p and miR-135a-5p suppress cell proliferation and migration in glioblastoma multiforme cells by inhibiting at the mRNA and protein levels. Taken together, our results provide novel regulatory mechanisms for at the post-transcriptional level and identify potential candidates for the treatment of patients with glioblastoma multiforme.

摘要

ELOVL脂肪酸延长酶6(ELOVL6)通过催化棕榈酸(C16:0)延长为硬脂酸(C18:0)以及棕榈油酸(C16:1n-7)延长为vaccinate(C18:1n-7)来控制细胞脂肪酸(FA)组成。尽管其转录调控已得到充分研究,但其转录后调控仍未完全阐明。因此,本研究旨在评估微小RNA(miRNA)在调控人类ELOVL6中的作用。生物信息学分析鉴定出五个假定的miRNA:miR-135b-5p、miR-135a-5p、miR-125a-5p、miR-125b-5p和miR-22-3p,它们可能与ELOVL6的3'非翻译区(UTR)结合。双荧光素酶检测结果显示,这些miRNA通过直接与ELOVL6 mRNA的3'-UTR相互作用而下调ELOVL6。此外,miR-135b-5p和miR-135a-5p通过在mRNA和蛋白质水平抑制ELOVL6来抑制多形性胶质母细胞瘤细胞的增殖和迁移。综上所述,我们的结果为ELOVL6在转录后水平提供了新的调控机制,并确定了多形性胶质母细胞瘤患者治疗的潜在候选物。

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