Abstract
Glioma invasion is a main cause of a poor prognosis and relapse in patients suffering from the disease. However, the molecular mechanisms responsible for glioma cell invasion remain poorly understood. In this study, the characteristics of exosomes were identified using electron microscope (TEM), and western blot analysis. The potential mechanism of long non‑coding RNA (lncRNA) activated by TGF‑β (lncRNA‑ATB) was demonstrated using luciferase reporter assays and RNA immunoprecipitation. We found that glioma cell‑derived exosomes promoted the activation of astrocytes and had the ability to shuttle long non‑coding RNA (lncRNA) activated by TGF‑β (lncRNA‑ATB) to astrocytes. More importantly, lncRNA‑ATB activated astrocytes through the suppression of microRNA (miRNA or miR)‑204‑3p in an Argonaute2 (Ago2)‑dependent manner. Furthermore, astrocytes activated by lncRNA‑ATB in turn promoted the migration and invasion of glioma cells. Taken together, the findings of this study suggest that lncRNA‑ATB may play an important role in modulating glioma microenvironment through exosomes. Thus, a better understanding of this process may provide implications for the prevention of highly invasive glioma.
Highlights
Despite the standard of care, consisting of surgical resection combined with chemotherapy and radiotherapy, the prognosisAbbreviations: GBM, glioblastoma multiforme; EVs, extracellular vesicles; MVBs, multivesicular bodies; lncRNAs, long non‐coding RNAs; lncRNA‐ATB, long non‐coding RNA activated by TGF‐β; HCC, hepatocellular carcinoma; EMT, epithelial‐mesenchymal transition; TEM, transmission electron microscopy; Normal human astrocytes (NHAs), normal human astrocytes; ceRNAs, competitive endogenous RNAsKey words: glioma, astrocytes, long non‐coding RNA‐ATB, microRNA‐204‐3p of patients with glioma remains dismal [1]
Exosomes purified from the media of the A172 and U251 glioma cells are shown in Fig. 1A, as visualized by TEM
The results revealed that the expression of miR‐204‐3p and miR‐200a was decreased by 69 and 46% in the lncRNA‐ATB vector‐transfected cells compared with the empty vector control‐transfected cells, respectively (Fig. 5B)
Summary
Despite the standard of care, consisting of surgical resection combined with chemotherapy and radiotherapy, the prognosis. The mechanisms underlying the communication between astrocytes and glioma cells are complex, and exosomes are likely involved
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