Abstract
BackgroundExtracellular 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.PurposesWe explored the specific cellular miRNAs and EV-miRNAs in medulloblastoma BTSCs to determine their potential biological function.MethodsBulk tumor cells (BTCs) and BTSCs were cultured under different conditions from medulloblastoma tissues (N = 10).ResultsTwenty-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.ConclusionOur results indicated that inhibition of miR-135b or miR-135a leads to suppress stemness of BTSC through modulation of AMOTL2.
Highlights
Extracellular vesicles (EVs) secreted by tumours, including exosomes, are important factors that regu‐ late cell–cell interactions in oncogenesis
Our results indicated that inhibition of miR-135b or miR-135a leads to suppress stemness of brain tumour spheroid-forming cells (BTSCs) through modulation of angiomotin-like 2 (AMOTL2)
Of the 10 patient samples, patient numbers 1–9 were used for all analyses, and number 10 was used only for functional analysis after validation of miR-135b, miR-135a and angiomotin-like 2 (AMOTL2) expression levels according to the analysis results
Summary
Extracellular vesicles (EVs) secreted by tumours, including exosomes, are important factors that regu‐ late cell–cell interactions in oncogenesis. Brain tumors contain small subpopulation cells with stem cell properties that play an important role in the tumor development, progression, metastasis and recurrence [1, 2]. These subpopulation cells have the ability spheroidforming ability and are enrichment of cancer stem cells (CSCs), called tumor initiating cells (TICs). They are known to be capable of self-renewal and differentiation into heterogeneous cancer cell lineages [3, 4].
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