MYCN‑amplified neuroblastoma cell‑derived exosomal miR‑17‑5p promotes proliferation and migration of non‑MYCN amplified cells

Abstract

Neuroblastoma (NB) is considered a highly prevalent extracranial solid tumor in young children, and the upregulation of N-myc proto-oncogene (MYCN) is closely associated with the late stages of NB and poor prognostic outcomes. The current study was designed to evaluate the effects of exosomal microRNA (miRNA/miR)-17-5p from MYCN-amplified NB cells on the proliferative and migratory potential of non-MYCN amplified NB cells. miR-17-5p was found to activate the PI3K/Akt signaling cascade by targeting PTEN, and the overexpression of miR-17-5p was found to promote cellular migration and proliferation in vitro . Further experimentation revealed that the elevated expression of miR-17-5p in SK-N-BE(2) cell-derived exosomes significantly promoted the proliferative and migratory capacities of SH-SY5Y cells by inhibiting PTEN. Collectively, these findings demonstrated that miR-17-5p derived from MYCN-amplified NB cell exosomes promoted the migration and proliferation of non-MYCN amplified cells, highlighting an exosome-associated malignant role for miR-17-5p.

MYC regulates metabolism through vesicular transfer of glycolytic kinases

“…It is not possible to exclude that the transfer of MYCN-regulated microRNAs might have contributed to some of the biological effects observed in our study. Indeed, two research groups have independently shown that microRNAs belonging to the 17–92 cluster are enriched in vesicles secreted by MYCN -amplified cells and their transfer stimulate proliferation and migration of recipient, MYCN non-amplified cells [ 45 , 46 ]. However, RNAi inhibition of PKM2 in MYCN- expressing donor cells completely reversed the increase in histone H3 phosphorylation in recipient MYCN single-copy cells, suggesting that this effect is regulated specifically by protein transfer.…”

Exosomes as Neurological Nanosized Machines

“…PTEN activates the PI3K/Akt signaling cascade and induces cell migration and proliferation, whereas NEDD4 is a onco-suppressor gene, pivotal in NB progression. 43,44 For these reasons, researchers suggested that tumor-derived exosomes become the target of new pharmaceutical studies for the inhibition of tumor spread. 43,44 Lastly, exosomes can be utilized in NB diagnosis.…”

“…43,44 For these reasons, researchers suggested that tumor-derived exosomes become the target of new pharmaceutical studies for the inhibition of tumor spread. 43,44 Lastly, exosomes can be utilized in NB diagnosis. Exosomes are optimal as noninvasive biomarkers for therapy monitoring and follow-ups.…”

“…They also carry miRNAs such as miR199a-3p and miR375 that promote tumor proliferation and migration via regulating NEDD4 and PTED expression, respectively. PTEN activates the PI3K/Akt signaling cascade and induces cell migration and proliferation, whereas NEDD4 is a onco-suppressor gene, pivotal in NB progression. , For these reasons, researchers suggested that tumor-derived exosomes become the target of new pharmaceutical studies for the inhibition of tumor spread. , …”

A systematic review of circulating-free MYCN amplification status as a noninvasive and prominent prognostic and recurrence monitoring indicator for neuroblastoma

“…Structurally, the MYCN coding region is highly homologous to the MYC gene coding region, and its expressed protein is about 60-63 kDa [29,30]. The MYCN protein plays an important role in cell signal transduction [31][32][33][34][35][36][37][38][39]. It is downstream of several important signal transduction pathways, such as the Wnt/β-catenin signaling pathway and PI3K/Akt/mTOR signaling pathway, etc.…”