MicroRNA-505-5p/-3p Regulates the Proliferation, Invasion, Apoptosis, and Temozolomide Resistance in Mesenchymal Glioma Stem Cells by Targeting AUF1.

Autor: Oe S; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Kakizaki R; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Sakamoto S; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Sato T; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Hayashi M; Department of Physiology, Institute of Biomedical Science, Kansai Medical University, Osaka, Hirakata, Japan., Isozaki H; Department of Neurosurgery, Kansai Medical University, Osaka, Hirakata, Japan., Nonaka M; Department of Neurosurgery, Kansai Medical University, Osaka, Hirakata, Japan., Iwashita H; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Hayashi S; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Koike T; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Seki-Omura R; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Nakano Y; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Sato Y; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan., Hirahara Y; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan.; Faculty of Nursing, Kansai Medical University, Osaka, Hirakata, Japan., Kitada M; Department of Anatomy, Kansai Medical University, Osaka, Hirakata, Japan.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2024 Nov 08. Date of Electronic Publication: 2024 Nov 08.
DOI: 10.1002/mc.23842
Abstrakt: Mesenchymal glioma stem cells (MES-GSCs) are a major subtype of GSCs that reside within glioma tissues and contribute to metastasis, therapy resistance, and glioma recurrence. However, the precise molecular mechanisms governing MES-GSC functions remain elusive. Our findings revealed that expression levels of miR-505-5p/-3p are elevated in MES-GSCs compared with those in proneural (PN)-GSCs, glioma cell lines, and normal brain tissue and that miR-505-5p/-3p expression levels are decreased in differentiated MES-GSCs. We assumed that miR-505-5p/-3p would play distinctive roles in MES-GSCs and performed loss-of-function experiments targeting miR-505-5p/-3p. Knockdown of miR-505-5p/-3p increased proliferation and promoted differentiation in MES-GSCs while suppressing invasion, temozolomide resistance, and enhancing apoptosis in MES-GSCs. Mechanistically, miR-505-5p/-3p directly targets the 3' UTR of AUF1, leading to its repression in MES-GSCs. Notably, AUF1 expression levels were significantly lower in MES-GSCs compared with those in PN-GSCs, glioma cell lines, and normal brain tissues. Co-inhibition of AUF1 expression with miR-505-5p/-3p knockdown ameliorated the observed cellular phenotypes caused by miR-505-5p/-3p knockdown in MES-GSCs. These results suggest that miR-505-5p/-3p exerts MES-GSC-specific roles in regulating proliferation, differentiation, invasion, apoptosis, and temozolomide resistance by repressing AUF1 expression.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
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