Extracellular vesicle-associated miR-135b and -135a regulate stemness in Group 4 medulloblastoma cells by targeting angiomotin-like 2

Autor: Seung Ah Choi, Eun Jung Koh, Ryong Nam Kim, Jung Woo Byun, Ji Hoon Phi, Jeyul Yang, Kyu-Chang Wang, Ae Kyung Park, Do Won Hwang, Ji Yeoun Lee, Seung-Ki Kim
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Cancer Cell International, Vol 20, Iss 1, Pp 1-14 (2020)
Druh dokumentu: article
ISSN: 1475-2867
DOI: 10.1186/s12935-020-01645-6
Popis: Abstract Background Extracellular vesicles (EVs) secreted by tumours, including exosomes, are important factors that regulate cell–cell interactions in oncogenesis. Although EV studies are ongoing, the biological understanding of EV-miRNAs derived from brain tumour spheroid-forming cells (BTSCs) of medulloblastoma is poor. Purposes We explored the specific cellular miRNAs and EV-miRNAs in medulloblastoma BTSCs to determine their potential biological function. Methods Bulk tumor cells (BTCs) and BTSCs were cultured under different conditions from medulloblastoma tissues (N = 10). Results Twenty-four miRNAs were simultaneously increased in both cells and EVs derived from BTSCs in comparison to BTCs. After inhibition of miR-135b or miR135a which were the most significantly increased in BTSCs, cell viability, self-renewal and stem cell marker expression decreased remarkably. Through integrated analysis of mRNAs and miRNAs data, we found that angiomotin-like 2 (AMOTL2), which was significantly decreased, was targeted by both miR-135b and miR-135a. STAT6 and GPX8 were targeted only by miR-135a. Importantly, low expression of AMOTL2 was significantly associated with overall poor survival in paediatric Group 3 and Group 4 medulloblastoma patients. Conclusion Our results indicated that inhibition of miR-135b or miR-135a leads to suppress stemness of BTSC through modulation of AMOTL2.
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