Recent evidence suggests that microRNAs (miRNAs) can be released to the extracellular microenvironment and mediate cell-cell communication through exosomes. The aim of this study was to identify exosomal miR-301a (exo-miR-301a) involved in glioblastoma (GBM) radioresistance and reveal the possible mechanisms. The exo-miR-301a specifically secreted by hypoxic GBM cells could transfer to corresponding normoxia-cultured cells and promote radiation resistance. Hypoxic exo-miR-301a directly targeted TCEAL7 genes, which were identified as a tumor suppressor in GBM malignancy and actively repressed its' expression in normoxic glioma cells. Our studies indicated that TCEAL7 negatively regulated the Wnt/ b-catenin pathway by blocking b-catenin translocation from cytoplasm to nucleus. Interestingly, we clarified that the Wnt/ b-catenin signaling was activated by miR-301a and TCEAL7 mediated the important procession. The exo-miR-301a was involved in the resistance to radiotherapy, and the effects would be reversed by miR-301a inhibition or TCEAL7 overexpression to regulate the Wnt/b-catenin axis. Here we show that exo-miR-301a, which is characteristically expressed and secreted by hypoxic glioma cells, is a potent regulator of Wnt/b-catenin and then depresses radiation sensitivity through targeting anti-oncogene TCEAL7. The newly identified exo-miR-301a/ TCEAL7-signaling axis could present a novel target for cellular resistance to cancer therapeutic radiation in GBM patients.

The study aimed to explore the specific function and mechanism of miR-144-3p in glioblastoma (GBM) cells with different phosphatase and tensin homolog (PTEN) phenotypes. We demonstrated that the miR-144-3p level was significantly down-regulated in glioma compared with the non-neoplastic brain tissues, and decreased with ascending grades. The loss of miR-144-3p effectively predicted the decreased overall survival in glioma patients. Interestingly, the expression of MET was up-regulated and inversely associated with miR-144-3p level in glioma tissues. Next, we certified that miR-144-3p specifically bound to MET 3 0 -untranslated region (3 0 UTR) and inhibited its expression. miR-144-3p potently repressed GBM cell proliferation and invasion via suppressing MET in vitro and in vivo. In addition, our results showed no difference in malignancy inhibition induced by miR-144-3p in GBM cells with different PTEN phenotypes. miR-144-3p inhibited several survival signaling pathways by targeting MET independent of PTEN status in GBM cells. Overexpression of miR-144-3p inhibited survival capability and increased apoptosis, resulting in enhancement of radiation and temozolomide sensitivity. Our data provide new insights into the potential application of miR-144-3p in GBM therapy by targeting MET and then inhibiting the downstream signaling.

Jahn–Teller distortion in cobalt based spinel electrocatalysts causes poor activity and stability in potentially promising catalysts for water splitting. Here, a novel strategy to resolve this problem by interface engineering is reported, in which, Jahn–Teller distortion in MnCo2O4 is significantly suppressed by in situ growth Ni2P nanosheets onto the MnCo2O4. The significance of interface engineering in suppressing Jahn–Teller distortion of Mn3+ is further investigated by X‐ray photoelectron spectroscopy, the resulting increased catalytic activity and the effects of suppressed distortion demonstrated by density functional theory calculations. The resulting MnCo2O4@Ni2P heterostructures exhibit superior electrocatalytic activity for the both oxygen evolution reaction and hydrogen evolution reaction with small overpotentials of 240 and 57 mV at 10 mA cm‐2, respectively. Furthermore, the heterogeneous composite electrode demonstrates a superior current density of 10 mA cm‐2 at a voltage of 1.63 V with excellent durability in a water splitting cell.

Our findings revealed the mechanism of action for miR-301a in tumor cell invasion. Moreover, the Wnt/miR-301a/SEPT7 signaling axis might be a novel target in treating glioma.